TBD Meeting (2893-22)

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

A version of this article first appeared on Medscape.com.

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

A version of this article first appeared on Medscape.com.

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

A version of this article first appeared on Medscape.com.

One year into treatment with an every-6-month dose of the investigational drug lenacapavir (LEN, Gilead Sciences) in a dual-treatment combination, 88% of treatment-naive people living with HIV had undetectable viral loads.

The findings, presented at the Conference on Retroviruses and Opportunistic Infections, also showed the drug was well tolerated, with 2 of 182 people developing drug-resistant mutations to lenacapavir and one person developing a nodule at the injection site.

Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust, who was not involved in the trial, called the findings “hugely exciting,” especially given its unique mode of administration. Right now it’s formulated as a subcutaneous injection, not an intramuscular injection like cabotegravir and rilpivirine (Cabenuva, ViiV Healthcare).

“Clearly it’s incredibly exciting to have the option for a subcutaneous drug that could be given at home every 6 months,” Dr. Waters said in an interview. With phase 3 trials and long-term follow-up still to come, she said she’s looking forward to how the treatment evolves.

CALIBRATE is a phase 2, four-arm, open-label, active-control study. Of the 182 participants, 25 were randomized to the active control arm, in which participants took daily oral bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy, Gilead Sciences) as standard of care. The rest of the 182 participants were divided evenly between three arms. In one of those, treatment group three, participants took a daily oral version of 50-mg LEN with emtricitabine and tenofovir alafenamide (F/TAF, Descovy, Gilead Sciences).

The other two arms, treatment groups one and two, were the arms in which Samir K. Gupta, MD, of Indiana University, Indianapolis, and colleagues tried the twice-yearly subcutaneous shots of LEN (LEN SC). Participants in those arms underwent a 2-week lead-in period in which they took 600 mg of LEN orally on days 1 and 2 and then a 300-mg pill on day 8 before starting the shots on day 15. As currently formulated, LEN SC shots can be given into the stomach and are designed to be simple enough to administer at home.

“It’s like doing an insulin shot,” Dr. Gupta said in an interview.

In addition to LEN SC, participants in treatment group one took a daily Descovy lead-in and then engaged in dual therapy of LEN plus TAF. In group two, they took a daily Descovy lead-in and then switched to LEN SC plus bictegravir (BIC) daily at 28 weeks.

Study results presented at the meeting were the results at 54 weeks. Researchers had previously presented 28-week results for CALIBRATE at the International AIDS Society Conference on HIV Science 2021.

Of the participants, 7% were cisgender women, 52% were Black, and 45% were Latinx. A total of 15% of participants had baseline viral loads of more than 100,000 copies, and median CD4 counts were 437. None of the participants in either the active-control arm or the LEN SC plus Descovy group had a history of AIDS, defined as fewer than 200 cells/mcL. In the LEN SC plus Biktarvy group, two did, and there were six people with a history of AIDS in the oral LEN plus Descovy group.

At 54 weeks, 88% of participants in groups one and two – the LEN SC arms – had undetectable viral loads (viral loads below 50 copies/mL). Specifically, 90% of those in the LEN SC plus TAF arm had viral loads below 50 copies. Those taking LEN SC plus BIC had an 85% viral suppression rate. The best performing of all was the control arm, in which 92% had undetectable viral loads. The protocol didn’t allow for analysis of statistical significance between the arms, so it’s unclear if any of the treatments really surpassed the others, Dr. Gupta said.

When they looked only at people whose viral loads became undetectable early, by week 28, the results were slightly better, with 93% of people between the two subcutaneous arms having undetectable viral loads at week 54. Again, the results were slightly higher in the LEN SC plus TAF arm (94%) than the LEN SC plus BIC (92%). People taking daily oral LEN plus Descovy had the lowest rate of viral suppression, but it was still at 90% if they were virally suppressed early. Again, it’s unclear whether those differences were statistically significant.
 

Well tolerated, with a chance of a nodule

Regarding safety, LEN was well tolerated across treatment arms, though the oral LEN group had as many people develop resistance mutations as the other three groups combined. Still, that was only three people, with one each in the two subcutaneous arms and one in the control arm.

Two people developed resistance to LEN – one in the LEN SC plus BIC arm and one in the oral LEN plus Descovy arm. In the LEN SC plus BIC arm, the mutations Q67H and K70R emerged at week 10, following a mutation that’s common when people don’t take integrase inhibitors as they’re supposed to (M184M/I). This led Dr. Gupta to conclude that lack of adherence to the oral part of the regimen may have contributed to the development of resistance, rather than an issue with LEN SC itself.

In the oral LEN plus Descovy arm, mutation Q67H didn’t emerge until week 54, when pill counts and drug levels revealed that that participant hadn’t been taking his Descovy as prescribed. In both cases, viral loads in those participants returned to undetectable after switching to an integrase inhibitor–based three-drug regimen.

Most safety concerns were mild and included nausea, diarrhea, and vomiting. But that was for non–injection-site reactions. There were more side effects of that sort, with most of them being pain, hardening of the site, and swelling. But 11% of participants developed more serious side effects, including nodules. Only one nodule was considered a grade 3 reaction; that person didn’t leave the trial because of it.

“These phase 2 data from the ongoing CALIBRATE trial support the further evaluation of lenacapavir for treatment and prevention of HIV-1,” he said.
 

Finding the right partner

In short, the findings are promising, Dr. Gupta told this news organization . But the question now, as Gilead prepares to begin a phase 3 efficacy trial, is what would be a good combination with LEN SC?

“Lenacapavir in a two-drug regimen should work,” he said. “The question now, though, is you have to find a suitable, potent, second agent to pair it with.”

Indeed, the long-acting HIV treatment pipeline sustained a blow in December 2021 when the U.S. Food and Drug Administration halted all trials for Merck’s investigational, long-acting drug islatravir. This led Dr. Waters to tweet: “Is it just me or are the islatravir abstracts at #CROI2022 quite sad to read?” She ended the tweet with, “I just hope it recovers!”

Indeed, Merck and Gilead have entered into an agreement to codevelop lenacapavir and islatravir as a weekly oral tablet. Islatravir seemed like the obvious choice as a partner to lenacapavir if phase 3 trials are successful, said Dr. Gupta. But now, it’s anyone’s guess as to what will happen. And while it’s too soon to say that lenacapavir is a success, it does leave the field wondering about how to use LEN SC without another, equally long-acting agent.

“When I talk about LEN, I show a picture of a man standing solo at a party, leaning against the wall looking a bit lonely, with ‘lenacapavir’ written over his head,” she said in an interview. “Right now, lenacapavir is the only drug at the 6-monthly party. It’s going to need some other guests if that party is going to rock.”

The study was funded by Gilead Sciences. Dr. Gupta has received research funding from ViiV Healthcare and advisory board fees from Gilead Sciences and ViiV Healthcare. Dr. Waters has received speaker or advisory fees from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

A version of this article first appeared on Medscape.com.

One year into treatment with an every-6-month dose of the investigational drug lenacapavir (LEN, Gilead Sciences) in a dual-treatment combination, 88% of treatment-naive people living with HIV had undetectable viral loads.

The findings, presented at the Conference on Retroviruses and Opportunistic Infections, also showed the drug was well tolerated, with 2 of 182 people developing drug-resistant mutations to lenacapavir and one person developing a nodule at the injection site.

Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust, who was not involved in the trial, called the findings “hugely exciting,” especially given its unique mode of administration. Right now it’s formulated as a subcutaneous injection, not an intramuscular injection like cabotegravir and rilpivirine (Cabenuva, ViiV Healthcare).

“Clearly it’s incredibly exciting to have the option for a subcutaneous drug that could be given at home every 6 months,” Dr. Waters said in an interview. With phase 3 trials and long-term follow-up still to come, she said she’s looking forward to how the treatment evolves.

CALIBRATE is a phase 2, four-arm, open-label, active-control study. Of the 182 participants, 25 were randomized to the active control arm, in which participants took daily oral bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy, Gilead Sciences) as standard of care. The rest of the 182 participants were divided evenly between three arms. In one of those, treatment group three, participants took a daily oral version of 50-mg LEN with emtricitabine and tenofovir alafenamide (F/TAF, Descovy, Gilead Sciences).

The other two arms, treatment groups one and two, were the arms in which Samir K. Gupta, MD, of Indiana University, Indianapolis, and colleagues tried the twice-yearly subcutaneous shots of LEN (LEN SC). Participants in those arms underwent a 2-week lead-in period in which they took 600 mg of LEN orally on days 1 and 2 and then a 300-mg pill on day 8 before starting the shots on day 15. As currently formulated, LEN SC shots can be given into the stomach and are designed to be simple enough to administer at home.

“It’s like doing an insulin shot,” Dr. Gupta said in an interview.

In addition to LEN SC, participants in treatment group one took a daily Descovy lead-in and then engaged in dual therapy of LEN plus TAF. In group two, they took a daily Descovy lead-in and then switched to LEN SC plus bictegravir (BIC) daily at 28 weeks.

Study results presented at the meeting were the results at 54 weeks. Researchers had previously presented 28-week results for CALIBRATE at the International AIDS Society Conference on HIV Science 2021.

Of the participants, 7% were cisgender women, 52% were Black, and 45% were Latinx. A total of 15% of participants had baseline viral loads of more than 100,000 copies, and median CD4 counts were 437. None of the participants in either the active-control arm or the LEN SC plus Descovy group had a history of AIDS, defined as fewer than 200 cells/mcL. In the LEN SC plus Biktarvy group, two did, and there were six people with a history of AIDS in the oral LEN plus Descovy group.

At 54 weeks, 88% of participants in groups one and two – the LEN SC arms – had undetectable viral loads (viral loads below 50 copies/mL). Specifically, 90% of those in the LEN SC plus TAF arm had viral loads below 50 copies. Those taking LEN SC plus BIC had an 85% viral suppression rate. The best performing of all was the control arm, in which 92% had undetectable viral loads. The protocol didn’t allow for analysis of statistical significance between the arms, so it’s unclear if any of the treatments really surpassed the others, Dr. Gupta said.

When they looked only at people whose viral loads became undetectable early, by week 28, the results were slightly better, with 93% of people between the two subcutaneous arms having undetectable viral loads at week 54. Again, the results were slightly higher in the LEN SC plus TAF arm (94%) than the LEN SC plus BIC (92%). People taking daily oral LEN plus Descovy had the lowest rate of viral suppression, but it was still at 90% if they were virally suppressed early. Again, it’s unclear whether those differences were statistically significant.
 

Well tolerated, with a chance of a nodule

Regarding safety, LEN was well tolerated across treatment arms, though the oral LEN group had as many people develop resistance mutations as the other three groups combined. Still, that was only three people, with one each in the two subcutaneous arms and one in the control arm.

Two people developed resistance to LEN – one in the LEN SC plus BIC arm and one in the oral LEN plus Descovy arm. In the LEN SC plus BIC arm, the mutations Q67H and K70R emerged at week 10, following a mutation that’s common when people don’t take integrase inhibitors as they’re supposed to (M184M/I). This led Dr. Gupta to conclude that lack of adherence to the oral part of the regimen may have contributed to the development of resistance, rather than an issue with LEN SC itself.

In the oral LEN plus Descovy arm, mutation Q67H didn’t emerge until week 54, when pill counts and drug levels revealed that that participant hadn’t been taking his Descovy as prescribed. In both cases, viral loads in those participants returned to undetectable after switching to an integrase inhibitor–based three-drug regimen.

Most safety concerns were mild and included nausea, diarrhea, and vomiting. But that was for non–injection-site reactions. There were more side effects of that sort, with most of them being pain, hardening of the site, and swelling. But 11% of participants developed more serious side effects, including nodules. Only one nodule was considered a grade 3 reaction; that person didn’t leave the trial because of it.

“These phase 2 data from the ongoing CALIBRATE trial support the further evaluation of lenacapavir for treatment and prevention of HIV-1,” he said.
 

Finding the right partner

In short, the findings are promising, Dr. Gupta told this news organization . But the question now, as Gilead prepares to begin a phase 3 efficacy trial, is what would be a good combination with LEN SC?

“Lenacapavir in a two-drug regimen should work,” he said. “The question now, though, is you have to find a suitable, potent, second agent to pair it with.”

Indeed, the long-acting HIV treatment pipeline sustained a blow in December 2021 when the U.S. Food and Drug Administration halted all trials for Merck’s investigational, long-acting drug islatravir. This led Dr. Waters to tweet: “Is it just me or are the islatravir abstracts at #CROI2022 quite sad to read?” She ended the tweet with, “I just hope it recovers!”

Indeed, Merck and Gilead have entered into an agreement to codevelop lenacapavir and islatravir as a weekly oral tablet. Islatravir seemed like the obvious choice as a partner to lenacapavir if phase 3 trials are successful, said Dr. Gupta. But now, it’s anyone’s guess as to what will happen. And while it’s too soon to say that lenacapavir is a success, it does leave the field wondering about how to use LEN SC without another, equally long-acting agent.

“When I talk about LEN, I show a picture of a man standing solo at a party, leaning against the wall looking a bit lonely, with ‘lenacapavir’ written over his head,” she said in an interview. “Right now, lenacapavir is the only drug at the 6-monthly party. It’s going to need some other guests if that party is going to rock.”

The study was funded by Gilead Sciences. Dr. Gupta has received research funding from ViiV Healthcare and advisory board fees from Gilead Sciences and ViiV Healthcare. Dr. Waters has received speaker or advisory fees from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

A version of this article first appeared on Medscape.com.

One year into treatment with an every-6-month dose of the investigational drug lenacapavir (LEN, Gilead Sciences) in a dual-treatment combination, 88% of treatment-naive people living with HIV had undetectable viral loads.

The findings, presented at the Conference on Retroviruses and Opportunistic Infections, also showed the drug was well tolerated, with 2 of 182 people developing drug-resistant mutations to lenacapavir and one person developing a nodule at the injection site.

Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust, who was not involved in the trial, called the findings “hugely exciting,” especially given its unique mode of administration. Right now it’s formulated as a subcutaneous injection, not an intramuscular injection like cabotegravir and rilpivirine (Cabenuva, ViiV Healthcare).

“Clearly it’s incredibly exciting to have the option for a subcutaneous drug that could be given at home every 6 months,” Dr. Waters said in an interview. With phase 3 trials and long-term follow-up still to come, she said she’s looking forward to how the treatment evolves.

CALIBRATE is a phase 2, four-arm, open-label, active-control study. Of the 182 participants, 25 were randomized to the active control arm, in which participants took daily oral bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy, Gilead Sciences) as standard of care. The rest of the 182 participants were divided evenly between three arms. In one of those, treatment group three, participants took a daily oral version of 50-mg LEN with emtricitabine and tenofovir alafenamide (F/TAF, Descovy, Gilead Sciences).

The other two arms, treatment groups one and two, were the arms in which Samir K. Gupta, MD, of Indiana University, Indianapolis, and colleagues tried the twice-yearly subcutaneous shots of LEN (LEN SC). Participants in those arms underwent a 2-week lead-in period in which they took 600 mg of LEN orally on days 1 and 2 and then a 300-mg pill on day 8 before starting the shots on day 15. As currently formulated, LEN SC shots can be given into the stomach and are designed to be simple enough to administer at home.

“It’s like doing an insulin shot,” Dr. Gupta said in an interview.

In addition to LEN SC, participants in treatment group one took a daily Descovy lead-in and then engaged in dual therapy of LEN plus TAF. In group two, they took a daily Descovy lead-in and then switched to LEN SC plus bictegravir (BIC) daily at 28 weeks.

Study results presented at the meeting were the results at 54 weeks. Researchers had previously presented 28-week results for CALIBRATE at the International AIDS Society Conference on HIV Science 2021.

Of the participants, 7% were cisgender women, 52% were Black, and 45% were Latinx. A total of 15% of participants had baseline viral loads of more than 100,000 copies, and median CD4 counts were 437. None of the participants in either the active-control arm or the LEN SC plus Descovy group had a history of AIDS, defined as fewer than 200 cells/mcL. In the LEN SC plus Biktarvy group, two did, and there were six people with a history of AIDS in the oral LEN plus Descovy group.

At 54 weeks, 88% of participants in groups one and two – the LEN SC arms – had undetectable viral loads (viral loads below 50 copies/mL). Specifically, 90% of those in the LEN SC plus TAF arm had viral loads below 50 copies. Those taking LEN SC plus BIC had an 85% viral suppression rate. The best performing of all was the control arm, in which 92% had undetectable viral loads. The protocol didn’t allow for analysis of statistical significance between the arms, so it’s unclear if any of the treatments really surpassed the others, Dr. Gupta said.

When they looked only at people whose viral loads became undetectable early, by week 28, the results were slightly better, with 93% of people between the two subcutaneous arms having undetectable viral loads at week 54. Again, the results were slightly higher in the LEN SC plus TAF arm (94%) than the LEN SC plus BIC (92%). People taking daily oral LEN plus Descovy had the lowest rate of viral suppression, but it was still at 90% if they were virally suppressed early. Again, it’s unclear whether those differences were statistically significant.
 

Well tolerated, with a chance of a nodule

Regarding safety, LEN was well tolerated across treatment arms, though the oral LEN group had as many people develop resistance mutations as the other three groups combined. Still, that was only three people, with one each in the two subcutaneous arms and one in the control arm.

Two people developed resistance to LEN – one in the LEN SC plus BIC arm and one in the oral LEN plus Descovy arm. In the LEN SC plus BIC arm, the mutations Q67H and K70R emerged at week 10, following a mutation that’s common when people don’t take integrase inhibitors as they’re supposed to (M184M/I). This led Dr. Gupta to conclude that lack of adherence to the oral part of the regimen may have contributed to the development of resistance, rather than an issue with LEN SC itself.

In the oral LEN plus Descovy arm, mutation Q67H didn’t emerge until week 54, when pill counts and drug levels revealed that that participant hadn’t been taking his Descovy as prescribed. In both cases, viral loads in those participants returned to undetectable after switching to an integrase inhibitor–based three-drug regimen.

Most safety concerns were mild and included nausea, diarrhea, and vomiting. But that was for non–injection-site reactions. There were more side effects of that sort, with most of them being pain, hardening of the site, and swelling. But 11% of participants developed more serious side effects, including nodules. Only one nodule was considered a grade 3 reaction; that person didn’t leave the trial because of it.

“These phase 2 data from the ongoing CALIBRATE trial support the further evaluation of lenacapavir for treatment and prevention of HIV-1,” he said.
 

Finding the right partner

In short, the findings are promising, Dr. Gupta told this news organization . But the question now, as Gilead prepares to begin a phase 3 efficacy trial, is what would be a good combination with LEN SC?

“Lenacapavir in a two-drug regimen should work,” he said. “The question now, though, is you have to find a suitable, potent, second agent to pair it with.”

Indeed, the long-acting HIV treatment pipeline sustained a blow in December 2021 when the U.S. Food and Drug Administration halted all trials for Merck’s investigational, long-acting drug islatravir. This led Dr. Waters to tweet: “Is it just me or are the islatravir abstracts at #CROI2022 quite sad to read?” She ended the tweet with, “I just hope it recovers!”

Indeed, Merck and Gilead have entered into an agreement to codevelop lenacapavir and islatravir as a weekly oral tablet. Islatravir seemed like the obvious choice as a partner to lenacapavir if phase 3 trials are successful, said Dr. Gupta. But now, it’s anyone’s guess as to what will happen. And while it’s too soon to say that lenacapavir is a success, it does leave the field wondering about how to use LEN SC without another, equally long-acting agent.

“When I talk about LEN, I show a picture of a man standing solo at a party, leaning against the wall looking a bit lonely, with ‘lenacapavir’ written over his head,” she said in an interview. “Right now, lenacapavir is the only drug at the 6-monthly party. It’s going to need some other guests if that party is going to rock.”

The study was funded by Gilead Sciences. Dr. Gupta has received research funding from ViiV Healthcare and advisory board fees from Gilead Sciences and ViiV Healthcare. Dr. Waters has received speaker or advisory fees from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

A version of this article first appeared on Medscape.com.

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

A version of this article first appeared on Medscape.com.

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

A version of this article first appeared on Medscape.com.

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

A version of this article first appeared on Medscape.com.

The recent news that a third person has been “cured” of HIV through a unique transplant of stem cells has given hope for a larger-scale way to beat back the HIV epidemic that has plagued the world for decades.

But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.

Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, told those attending the Conference on Retroviruses and Opportunistic Infections that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latinx.

The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.

The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers said.

While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. Overall, Dr. Bryson estimates that about 50 people per year may benefit from this procedure. 

Even so, other experts say the approach could provide insight into other ways to find cures. And Dr. Bryson says it opens up options for more diverse populations.

“A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured,” said Sharon Lewin, MD, president-elect of the International AIDS Society. “It also further strengthens using gene therapy as a viable strategy for an HIV cure.”

The woman needed a stem cell transplant after being diagnosed with leukemia. The stem cell transplant technique used was also novel, Dr. Bryson said. The medical team used a combination of adult stem cells from a relative’s blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.

In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.

The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers said. By day 100 after the transplant, Dr. Bryson said, the woman basically had a new immune system.

HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the antiretroviral treatment commonly given to treat HIV infection.

‘’She is currently clinically well,” Dr. Bryson said. Her cancer is in remission.
 

Case histories: Three patients

The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia. The transplant was done to treat that.

Her recovery was much less bumpy than that of the previous two patients, the researchers said. She left the hospital 17 days after the transplant. She didn’t have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.

“This case also suggests that it’s the transplant of HIV-resistant cells that was key to achieving a cure here,” said Dr. Lewin. The first patient who had HIV remission after a stem cell transplant, a White man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latinx man, has been in remission for more than 30 months.
 

HIV statistics, ethnic/racial burdens

In the United States, about 1.2 million people have HIV, according to HIV.gov. Thirteen percent of those who have it do not know they have it. In 2019, 34,800 new infections were diagnosed.

Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinx represented 18.5% of the total population but 25% of those diagnosed with HIV.

Disparities also affect women unequally, with Black women disproportionately affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of White women and 4 times that of Latinx, according to federal statistics.
 

Expert perspective, reactions

Vincent Marconi, MD, professor of infectious diseases at Emory University, Atlanta, whose research focuses on disparities in HIV treatment responses, called the news “an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects.”

Although the approach, meant to be used to treat the cancers, will not be widely available, he said that ‘’it does provide insight into somewhat related alternative models of cure involving gene therapy.”

Meanwhile, Dr. Marconi and other researchers are focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.

A version of this article first appeared on WebMD.com.

The recent news that a third person has been “cured” of HIV through a unique transplant of stem cells has given hope for a larger-scale way to beat back the HIV epidemic that has plagued the world for decades.

But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.

Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, told those attending the Conference on Retroviruses and Opportunistic Infections that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latinx.

The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.

The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers said.

While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. Overall, Dr. Bryson estimates that about 50 people per year may benefit from this procedure. 

Even so, other experts say the approach could provide insight into other ways to find cures. And Dr. Bryson says it opens up options for more diverse populations.

“A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured,” said Sharon Lewin, MD, president-elect of the International AIDS Society. “It also further strengthens using gene therapy as a viable strategy for an HIV cure.”

The woman needed a stem cell transplant after being diagnosed with leukemia. The stem cell transplant technique used was also novel, Dr. Bryson said. The medical team used a combination of adult stem cells from a relative’s blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.

In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.

The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers said. By day 100 after the transplant, Dr. Bryson said, the woman basically had a new immune system.

HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the antiretroviral treatment commonly given to treat HIV infection.

‘’She is currently clinically well,” Dr. Bryson said. Her cancer is in remission.
 

Case histories: Three patients

The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia. The transplant was done to treat that.

Her recovery was much less bumpy than that of the previous two patients, the researchers said. She left the hospital 17 days after the transplant. She didn’t have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.

“This case also suggests that it’s the transplant of HIV-resistant cells that was key to achieving a cure here,” said Dr. Lewin. The first patient who had HIV remission after a stem cell transplant, a White man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latinx man, has been in remission for more than 30 months.
 

HIV statistics, ethnic/racial burdens

In the United States, about 1.2 million people have HIV, according to HIV.gov. Thirteen percent of those who have it do not know they have it. In 2019, 34,800 new infections were diagnosed.

Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinx represented 18.5% of the total population but 25% of those diagnosed with HIV.

Disparities also affect women unequally, with Black women disproportionately affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of White women and 4 times that of Latinx, according to federal statistics.
 

Expert perspective, reactions

Vincent Marconi, MD, professor of infectious diseases at Emory University, Atlanta, whose research focuses on disparities in HIV treatment responses, called the news “an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects.”

Although the approach, meant to be used to treat the cancers, will not be widely available, he said that ‘’it does provide insight into somewhat related alternative models of cure involving gene therapy.”

Meanwhile, Dr. Marconi and other researchers are focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.

A version of this article first appeared on WebMD.com.

The recent news that a third person has been “cured” of HIV through a unique transplant of stem cells has given hope for a larger-scale way to beat back the HIV epidemic that has plagued the world for decades.

But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.

Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, told those attending the Conference on Retroviruses and Opportunistic Infections that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latinx.

The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.

The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers said.

While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. Overall, Dr. Bryson estimates that about 50 people per year may benefit from this procedure. 

Even so, other experts say the approach could provide insight into other ways to find cures. And Dr. Bryson says it opens up options for more diverse populations.

“A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured,” said Sharon Lewin, MD, president-elect of the International AIDS Society. “It also further strengthens using gene therapy as a viable strategy for an HIV cure.”

The woman needed a stem cell transplant after being diagnosed with leukemia. The stem cell transplant technique used was also novel, Dr. Bryson said. The medical team used a combination of adult stem cells from a relative’s blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.

In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.

The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers said. By day 100 after the transplant, Dr. Bryson said, the woman basically had a new immune system.

HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the antiretroviral treatment commonly given to treat HIV infection.

‘’She is currently clinically well,” Dr. Bryson said. Her cancer is in remission.
 

Case histories: Three patients

The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia. The transplant was done to treat that.

Her recovery was much less bumpy than that of the previous two patients, the researchers said. She left the hospital 17 days after the transplant. She didn’t have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.

“This case also suggests that it’s the transplant of HIV-resistant cells that was key to achieving a cure here,” said Dr. Lewin. The first patient who had HIV remission after a stem cell transplant, a White man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latinx man, has been in remission for more than 30 months.
 

HIV statistics, ethnic/racial burdens

In the United States, about 1.2 million people have HIV, according to HIV.gov. Thirteen percent of those who have it do not know they have it. In 2019, 34,800 new infections were diagnosed.

Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinx represented 18.5% of the total population but 25% of those diagnosed with HIV.

Disparities also affect women unequally, with Black women disproportionately affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of White women and 4 times that of Latinx, according to federal statistics.
 

Expert perspective, reactions

Vincent Marconi, MD, professor of infectious diseases at Emory University, Atlanta, whose research focuses on disparities in HIV treatment responses, called the news “an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects.”

Although the approach, meant to be used to treat the cancers, will not be widely available, he said that ‘’it does provide insight into somewhat related alternative models of cure involving gene therapy.”

Meanwhile, Dr. Marconi and other researchers are focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.

A version of this article first appeared on WebMD.com.

Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.

Medscape Illustration/Dreamstime/Getty Images

More than 1 in 10

About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.

The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
 

Ready to define long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.

Medscape Illustration/Dreamstime/Getty Images

More than 1 in 10

About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.

The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
 

Ready to define long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.

Medscape Illustration/Dreamstime/Getty Images

More than 1 in 10

About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.

The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
 

Ready to define long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Hours after their births, 34 infants began a three-drug combination HIV treatment. Now, 2 years later, a third of those toddlers have tested negative for HIV antibodies and have no detectable HIV DNA in their blood. The children aren’t cured of HIV, but as many as 16 of them may be candidates to stop treatment and see if they are in fact in HIV remission.

If one or more are, it would be the first time since the Mississippi baby in 2013 that scientists have induced childhood HIV remission by beginning HIV treatment very early.    

At the Conference on Retroviruses and Opportunistic Infections, Deborah Persaud, MD, interim director of pediatric infectious diseases and professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, Md., told this news organization that the evidence suggests that more U.S. clinicians should start infants at high risk for HIV on presumptive treatment – not only to potentially prevent transmission but also to set the child up for the lowest possible viral reservoir, the first step to HIV remission.

The three-drug preemptive treatment is “not uniformly practiced,” Dr. Persaud said in an interview. “We’re at a point now where we don’t have to wait to see if we have remission” to act on these findings, she said. “The question is, should this now become standard of care for in-utero infected infants?” 

Every year, about 150 infants are born with HIV in the United States, according to the Elizabeth Glaser Pediatric AIDS Foundation. Current U.S. perinatal treatment guidelines already suggest either treatment with one or more HIV drugs at birth to attempt preventing transmission or initiating three-drug regimens for infants at high risk for perinatally acquired HIV. In this case “high risk” is defined as infants born to:

• people who haven’t received any HIV treatment before delivery or during delivery,
• people who did receive treatment but failed to achieve undetectable viral loads, or
• people who acquire HIV during pregnancy, or who otherwise weren’t diagnosed until after birth.

Trying to replicate the Mississippi baby

The Mississippi baby did eventually relapse. But ever since Dr. Persaud reported the case of that 2-year-old who went into treatment-free remission in 2013, she has been trying to figure out how to duplicate that initial success. There were several factors in that remission, but one piece researchers could control was starting treatment very early – before HIV blood tests even come back positive. So, in this trial, researchers enrolled 440 infants in Africa and Asia at high risk for in utero HIV transmission.

All 440 of those infants received their first doses of the three-drug preemptive treatment within 24 hours of birth. Of those 440 infants, 34 tested positive for HIV and remained in the trial.*

Meanwhile, in North America, South America, and African countries, another 20 infants enrolled in the trial – not as part of the protocol but because their clinicians had been influenced by the news of the Mississippi baby, Dr. Persaud said, and decided on their own to start high-risk infants on three-drug regimens preemptively.

“We wanted to take advantage of those real-world situations of infants being treated outside the clinical trials,” Dr. Persaud said.

Now there were 54 infants trying this very early treatment. In Cohort One, they started their first drug cocktail 7 hours after delivery. In Cohort Two, their first antiretroviral combination treatment was at 32.8 hours of life, and they enrolled in the trial at 8 days. Then researchers followed the infants closely, adding on lopinavir and ritonavir when age-appropriate.
 

Meeting milestones

To continue in the trial and be considered for treatment interruption, infants had to meet certain milestones. At 24 weeks, HIV RNA needed to be below 200 copies per milliliter. Then their HIV RNA needed to stay below 200 copies consistently until week 48. At week 48, they had to have an HIV RNA that was even lower – below 20 or 40 copies – with “target not detected” in the test in HIV RNA. That’s a sign that there weren’t even any trace levels of viral nucleic acid RNA in the blood to indicate HIV. Then, from week 48 on, they had to maintain that level of viral suppression until age 2.

At that point, not only did they need to maintain that level of viral suppression, they also needed to have a negative HIV antibody test and a PCR test for total HIV DNA, which had to be undetectable down to the limit of 4 copies per 106 – that is, there were fewer than 4 copies of the virus out of 1 million cells tested. Only then would they be considered for treatment interruption.

“After week 28 there was no leeway,” Dr. Persaud said. Then “they had to have nothing detectable from the first year of age. We thought the best shot at remission were cases that achieved very good and strict virologic control.”

 

Criteria for consideration

Of the 34 infants in Cohort One, 24 infants made it past the first hurdle at 24 weeks and 6 had PCR tests that found no cell-associated HIV DNA. In Cohort Two, 15 made it past the week-24 hurdle and 4 had no detectable HIV DNA via PCR test.

Now, more than 2 years out from study initiation, Dr. Persaud and colleagues are evaluating each child to see if any still meet the requirements for treatment interruption. The COVID-19 pandemic has delayed their evaluations, and it’s possible that fewer children now meet the requirements. But Dr. Persaud said there are still candidates left. An analysis suggests that up to 30% of the children, or 16, were candidates at 2 years.

“We have kids who are eligible for [antiretroviral therapy] cessation years out from this, which I think is really important,” she said in an interview. “It’s not game over.”

And although 30% is not an overwhelming victory, Dr. Persaud said the team’s goal was “to identify an N of 1 to replicate the Mississippi baby.” The study team, led by Ellen Chadwick, MD, of Northwestern University’s Feinberg School of Medicine, Chicago, and a member of the board that creates HIV perinatal treatment guidelines, is starting a new trial, using more modern, integrase inhibitor-based, three-drug regimens for infants and pairing them with broadly neutralizing antibodies. The combination used in this trial included zidovudine, or AZT.

If one of the children is able to go off treatment, it would be the first step toward creating a functional cure for HIV, starting with the youngest people affected by the virus.  

“This trial convinces me that very early treatment was the key strategy that led to remission in the Mississippi baby,” Dr. Persaud said in an interview. “We’re confirming here that the first step toward remission and cure is reducing reservoirs. We’ve got that here. Whether we need more on top of that – therapeutic vaccines, immunotherapies, or a better regimen to start out with – needs to be determined.”

The presentation was met with excitement and questions. For instance, if very early treatment works, why does it work for just 30% of the children?

Were some of the children able to control HIV on their own because they were rare post-treatment controllers? And was 30% really a victory? Others were convinced of it.

“Amazing outcome to have 30% so well suppressed after 2 years with CA-DNA not detected,” commented Hermione Lyall, MBChB, a pediatric infectious disease doctor at Imperial College Healthcare NHS Trust in the United Kingdom, in the virtual chat.

As for whether the study should change practice, Elaine Abrams, MD, professor of epidemiology and pediatrics at Columbia University Medical Center, New York, and CROI cochair, said that this study proves that the three-drug regimen is at the very least safe to start immediately.

Whether it should become standard of care everywhere is still up for discussion, she told this news organization.

“It very much depends on what you’re trying to achieve,” she said. “Postnatal prophylaxis is provided to reduce the risk of acquiring infection. That’s a different objective than early treatment. If you have 1,000 high-risk babies, how many are likely to turn out to have HIV infection? And how many of those will you be treating with three drugs and actually making this impact by doing so? And how many babies are going to be getting possibly extra treatment that they don’t need?”

Regardless, what’s clear is that treatment is essential – for mother and infant, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases. It needs to start, he said, by making sure all mothers know their HIV status and have access early in pregnancy to the treatment that can prevent transmission.

“So much of what’s wrong in the world is about implementation of health care,” he said in an interview. Still, “if you could demonstrate that early treatment to the mother plus early treatment to the babies [is efficacious], we could really talk about an HIV-free generation of kids.”

The study was funded by the National Institutes of Health. Dr. Persaud, Dr. Dieffenbach, Dr. Abrams, and Dr. Lyall all report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Correction, 2/16/22: An earlier version of this article misstated the number that tested positive for HIV and remained in the trial.

This article was updated 2/16/22.

Hours after their births, 34 infants began a three-drug combination HIV treatment. Now, 2 years later, a third of those toddlers have tested negative for HIV antibodies and have no detectable HIV DNA in their blood. The children aren’t cured of HIV, but as many as 16 of them may be candidates to stop treatment and see if they are in fact in HIV remission.

If one or more are, it would be the first time since the Mississippi baby in 2013 that scientists have induced childhood HIV remission by beginning HIV treatment very early.    

At the Conference on Retroviruses and Opportunistic Infections, Deborah Persaud, MD, interim director of pediatric infectious diseases and professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, Md., told this news organization that the evidence suggests that more U.S. clinicians should start infants at high risk for HIV on presumptive treatment – not only to potentially prevent transmission but also to set the child up for the lowest possible viral reservoir, the first step to HIV remission.

The three-drug preemptive treatment is “not uniformly practiced,” Dr. Persaud said in an interview. “We’re at a point now where we don’t have to wait to see if we have remission” to act on these findings, she said. “The question is, should this now become standard of care for in-utero infected infants?” 

Every year, about 150 infants are born with HIV in the United States, according to the Elizabeth Glaser Pediatric AIDS Foundation. Current U.S. perinatal treatment guidelines already suggest either treatment with one or more HIV drugs at birth to attempt preventing transmission or initiating three-drug regimens for infants at high risk for perinatally acquired HIV. In this case “high risk” is defined as infants born to:

• people who haven’t received any HIV treatment before delivery or during delivery,
• people who did receive treatment but failed to achieve undetectable viral loads, or
• people who acquire HIV during pregnancy, or who otherwise weren’t diagnosed until after birth.

Trying to replicate the Mississippi baby

The Mississippi baby did eventually relapse. But ever since Dr. Persaud reported the case of that 2-year-old who went into treatment-free remission in 2013, she has been trying to figure out how to duplicate that initial success. There were several factors in that remission, but one piece researchers could control was starting treatment very early – before HIV blood tests even come back positive. So, in this trial, researchers enrolled 440 infants in Africa and Asia at high risk for in utero HIV transmission.

All 440 of those infants received their first doses of the three-drug preemptive treatment within 24 hours of birth. Of those 440 infants, 34 tested positive for HIV and remained in the trial.*

Meanwhile, in North America, South America, and African countries, another 20 infants enrolled in the trial – not as part of the protocol but because their clinicians had been influenced by the news of the Mississippi baby, Dr. Persaud said, and decided on their own to start high-risk infants on three-drug regimens preemptively.

“We wanted to take advantage of those real-world situations of infants being treated outside the clinical trials,” Dr. Persaud said.

Now there were 54 infants trying this very early treatment. In Cohort One, they started their first drug cocktail 7 hours after delivery. In Cohort Two, their first antiretroviral combination treatment was at 32.8 hours of life, and they enrolled in the trial at 8 days. Then researchers followed the infants closely, adding on lopinavir and ritonavir when age-appropriate.
 

Meeting milestones

To continue in the trial and be considered for treatment interruption, infants had to meet certain milestones. At 24 weeks, HIV RNA needed to be below 200 copies per milliliter. Then their HIV RNA needed to stay below 200 copies consistently until week 48. At week 48, they had to have an HIV RNA that was even lower – below 20 or 40 copies – with “target not detected” in the test in HIV RNA. That’s a sign that there weren’t even any trace levels of viral nucleic acid RNA in the blood to indicate HIV. Then, from week 48 on, they had to maintain that level of viral suppression until age 2.

At that point, not only did they need to maintain that level of viral suppression, they also needed to have a negative HIV antibody test and a PCR test for total HIV DNA, which had to be undetectable down to the limit of 4 copies per 106 – that is, there were fewer than 4 copies of the virus out of 1 million cells tested. Only then would they be considered for treatment interruption.

“After week 28 there was no leeway,” Dr. Persaud said. Then “they had to have nothing detectable from the first year of age. We thought the best shot at remission were cases that achieved very good and strict virologic control.”

 

Criteria for consideration

Of the 34 infants in Cohort One, 24 infants made it past the first hurdle at 24 weeks and 6 had PCR tests that found no cell-associated HIV DNA. In Cohort Two, 15 made it past the week-24 hurdle and 4 had no detectable HIV DNA via PCR test.

Now, more than 2 years out from study initiation, Dr. Persaud and colleagues are evaluating each child to see if any still meet the requirements for treatment interruption. The COVID-19 pandemic has delayed their evaluations, and it’s possible that fewer children now meet the requirements. But Dr. Persaud said there are still candidates left. An analysis suggests that up to 30% of the children, or 16, were candidates at 2 years.

“We have kids who are eligible for [antiretroviral therapy] cessation years out from this, which I think is really important,” she said in an interview. “It’s not game over.”

And although 30% is not an overwhelming victory, Dr. Persaud said the team’s goal was “to identify an N of 1 to replicate the Mississippi baby.” The study team, led by Ellen Chadwick, MD, of Northwestern University’s Feinberg School of Medicine, Chicago, and a member of the board that creates HIV perinatal treatment guidelines, is starting a new trial, using more modern, integrase inhibitor-based, three-drug regimens for infants and pairing them with broadly neutralizing antibodies. The combination used in this trial included zidovudine, or AZT.

If one of the children is able to go off treatment, it would be the first step toward creating a functional cure for HIV, starting with the youngest people affected by the virus.  

“This trial convinces me that very early treatment was the key strategy that led to remission in the Mississippi baby,” Dr. Persaud said in an interview. “We’re confirming here that the first step toward remission and cure is reducing reservoirs. We’ve got that here. Whether we need more on top of that – therapeutic vaccines, immunotherapies, or a better regimen to start out with – needs to be determined.”

The presentation was met with excitement and questions. For instance, if very early treatment works, why does it work for just 30% of the children?

Were some of the children able to control HIV on their own because they were rare post-treatment controllers? And was 30% really a victory? Others were convinced of it.

“Amazing outcome to have 30% so well suppressed after 2 years with CA-DNA not detected,” commented Hermione Lyall, MBChB, a pediatric infectious disease doctor at Imperial College Healthcare NHS Trust in the United Kingdom, in the virtual chat.

As for whether the study should change practice, Elaine Abrams, MD, professor of epidemiology and pediatrics at Columbia University Medical Center, New York, and CROI cochair, said that this study proves that the three-drug regimen is at the very least safe to start immediately.

Whether it should become standard of care everywhere is still up for discussion, she told this news organization.

“It very much depends on what you’re trying to achieve,” she said. “Postnatal prophylaxis is provided to reduce the risk of acquiring infection. That’s a different objective than early treatment. If you have 1,000 high-risk babies, how many are likely to turn out to have HIV infection? And how many of those will you be treating with three drugs and actually making this impact by doing so? And how many babies are going to be getting possibly extra treatment that they don’t need?”

Regardless, what’s clear is that treatment is essential – for mother and infant, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases. It needs to start, he said, by making sure all mothers know their HIV status and have access early in pregnancy to the treatment that can prevent transmission.

“So much of what’s wrong in the world is about implementation of health care,” he said in an interview. Still, “if you could demonstrate that early treatment to the mother plus early treatment to the babies [is efficacious], we could really talk about an HIV-free generation of kids.”

The study was funded by the National Institutes of Health. Dr. Persaud, Dr. Dieffenbach, Dr. Abrams, and Dr. Lyall all report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Correction, 2/16/22: An earlier version of this article misstated the number that tested positive for HIV and remained in the trial.

This article was updated 2/16/22.

Hours after their births, 34 infants began a three-drug combination HIV treatment. Now, 2 years later, a third of those toddlers have tested negative for HIV antibodies and have no detectable HIV DNA in their blood. The children aren’t cured of HIV, but as many as 16 of them may be candidates to stop treatment and see if they are in fact in HIV remission.

If one or more are, it would be the first time since the Mississippi baby in 2013 that scientists have induced childhood HIV remission by beginning HIV treatment very early.    

At the Conference on Retroviruses and Opportunistic Infections, Deborah Persaud, MD, interim director of pediatric infectious diseases and professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, Md., told this news organization that the evidence suggests that more U.S. clinicians should start infants at high risk for HIV on presumptive treatment – not only to potentially prevent transmission but also to set the child up for the lowest possible viral reservoir, the first step to HIV remission.

The three-drug preemptive treatment is “not uniformly practiced,” Dr. Persaud said in an interview. “We’re at a point now where we don’t have to wait to see if we have remission” to act on these findings, she said. “The question is, should this now become standard of care for in-utero infected infants?” 

Every year, about 150 infants are born with HIV in the United States, according to the Elizabeth Glaser Pediatric AIDS Foundation. Current U.S. perinatal treatment guidelines already suggest either treatment with one or more HIV drugs at birth to attempt preventing transmission or initiating three-drug regimens for infants at high risk for perinatally acquired HIV. In this case “high risk” is defined as infants born to:

• people who haven’t received any HIV treatment before delivery or during delivery,
• people who did receive treatment but failed to achieve undetectable viral loads, or
• people who acquire HIV during pregnancy, or who otherwise weren’t diagnosed until after birth.

Trying to replicate the Mississippi baby

The Mississippi baby did eventually relapse. But ever since Dr. Persaud reported the case of that 2-year-old who went into treatment-free remission in 2013, she has been trying to figure out how to duplicate that initial success. There were several factors in that remission, but one piece researchers could control was starting treatment very early – before HIV blood tests even come back positive. So, in this trial, researchers enrolled 440 infants in Africa and Asia at high risk for in utero HIV transmission.

All 440 of those infants received their first doses of the three-drug preemptive treatment within 24 hours of birth. Of those 440 infants, 34 tested positive for HIV and remained in the trial.*

Meanwhile, in North America, South America, and African countries, another 20 infants enrolled in the trial – not as part of the protocol but because their clinicians had been influenced by the news of the Mississippi baby, Dr. Persaud said, and decided on their own to start high-risk infants on three-drug regimens preemptively.

“We wanted to take advantage of those real-world situations of infants being treated outside the clinical trials,” Dr. Persaud said.

Now there were 54 infants trying this very early treatment. In Cohort One, they started their first drug cocktail 7 hours after delivery. In Cohort Two, their first antiretroviral combination treatment was at 32.8 hours of life, and they enrolled in the trial at 8 days. Then researchers followed the infants closely, adding on lopinavir and ritonavir when age-appropriate.
 

Meeting milestones

To continue in the trial and be considered for treatment interruption, infants had to meet certain milestones. At 24 weeks, HIV RNA needed to be below 200 copies per milliliter. Then their HIV RNA needed to stay below 200 copies consistently until week 48. At week 48, they had to have an HIV RNA that was even lower – below 20 or 40 copies – with “target not detected” in the test in HIV RNA. That’s a sign that there weren’t even any trace levels of viral nucleic acid RNA in the blood to indicate HIV. Then, from week 48 on, they had to maintain that level of viral suppression until age 2.

At that point, not only did they need to maintain that level of viral suppression, they also needed to have a negative HIV antibody test and a PCR test for total HIV DNA, which had to be undetectable down to the limit of 4 copies per 106 – that is, there were fewer than 4 copies of the virus out of 1 million cells tested. Only then would they be considered for treatment interruption.

“After week 28 there was no leeway,” Dr. Persaud said. Then “they had to have nothing detectable from the first year of age. We thought the best shot at remission were cases that achieved very good and strict virologic control.”

 

Criteria for consideration

Of the 34 infants in Cohort One, 24 infants made it past the first hurdle at 24 weeks and 6 had PCR tests that found no cell-associated HIV DNA. In Cohort Two, 15 made it past the week-24 hurdle and 4 had no detectable HIV DNA via PCR test.

Now, more than 2 years out from study initiation, Dr. Persaud and colleagues are evaluating each child to see if any still meet the requirements for treatment interruption. The COVID-19 pandemic has delayed their evaluations, and it’s possible that fewer children now meet the requirements. But Dr. Persaud said there are still candidates left. An analysis suggests that up to 30% of the children, or 16, were candidates at 2 years.

“We have kids who are eligible for [antiretroviral therapy] cessation years out from this, which I think is really important,” she said in an interview. “It’s not game over.”

And although 30% is not an overwhelming victory, Dr. Persaud said the team’s goal was “to identify an N of 1 to replicate the Mississippi baby.” The study team, led by Ellen Chadwick, MD, of Northwestern University’s Feinberg School of Medicine, Chicago, and a member of the board that creates HIV perinatal treatment guidelines, is starting a new trial, using more modern, integrase inhibitor-based, three-drug regimens for infants and pairing them with broadly neutralizing antibodies. The combination used in this trial included zidovudine, or AZT.

If one of the children is able to go off treatment, it would be the first step toward creating a functional cure for HIV, starting with the youngest people affected by the virus.  

“This trial convinces me that very early treatment was the key strategy that led to remission in the Mississippi baby,” Dr. Persaud said in an interview. “We’re confirming here that the first step toward remission and cure is reducing reservoirs. We’ve got that here. Whether we need more on top of that – therapeutic vaccines, immunotherapies, or a better regimen to start out with – needs to be determined.”

The presentation was met with excitement and questions. For instance, if very early treatment works, why does it work for just 30% of the children?

Were some of the children able to control HIV on their own because they were rare post-treatment controllers? And was 30% really a victory? Others were convinced of it.

“Amazing outcome to have 30% so well suppressed after 2 years with CA-DNA not detected,” commented Hermione Lyall, MBChB, a pediatric infectious disease doctor at Imperial College Healthcare NHS Trust in the United Kingdom, in the virtual chat.

As for whether the study should change practice, Elaine Abrams, MD, professor of epidemiology and pediatrics at Columbia University Medical Center, New York, and CROI cochair, said that this study proves that the three-drug regimen is at the very least safe to start immediately.

Whether it should become standard of care everywhere is still up for discussion, she told this news organization.

“It very much depends on what you’re trying to achieve,” she said. “Postnatal prophylaxis is provided to reduce the risk of acquiring infection. That’s a different objective than early treatment. If you have 1,000 high-risk babies, how many are likely to turn out to have HIV infection? And how many of those will you be treating with three drugs and actually making this impact by doing so? And how many babies are going to be getting possibly extra treatment that they don’t need?”

Regardless, what’s clear is that treatment is essential – for mother and infant, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases. It needs to start, he said, by making sure all mothers know their HIV status and have access early in pregnancy to the treatment that can prevent transmission.

“So much of what’s wrong in the world is about implementation of health care,” he said in an interview. Still, “if you could demonstrate that early treatment to the mother plus early treatment to the babies [is efficacious], we could really talk about an HIV-free generation of kids.”

The study was funded by the National Institutes of Health. Dr. Persaud, Dr. Dieffenbach, Dr. Abrams, and Dr. Lyall all report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Correction, 2/16/22: An earlier version of this article misstated the number that tested positive for HIV and remained in the trial.

This article was updated 2/16/22.

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.