US funding freeze threatens two decades' progress in HIV
The global HIV response faces serious disruption due to cuts in US government funding, the closure of USAID, and uncertainty about future financing, warned Professor Chris Beyrer, Director of the Duke Global Health Institute, in his plenary address to the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco this week.
Although the new administration has banned the words diversity, equity and inclusion, Beyrer said these values were essential to the global HIV response. “We can’t not address diversity because we are dealing with a diverse pandemic,” he said.
“The achievement of getting three-quarters of people living with HIV living on this planet onto antiretroviral therapy is the greatest achievement of equity in global health.”
Despite this achievement, the global HIV response was already falling short of targets before the new US administration began cutting funding. AIDS-related deaths remain far above the 2025 target, while HIV incidence stays stubbornly high at over a million new infections per year.
Primary prevention programmes would need to be expanded to achieve a sustained reduction in HIV incidence. An estimated 40 million people would need to start PrEP in sub-Saharan Africa, according to modelling.
Beyrer highlighted that 91% of all oral PrEP starts globally have been funded by PEPFAR. However, apart from prevention of mother-to-child transmission, "prevention in PEPFAR is now on pause." A waiver issued by US Secretary of State Marco Rubio on 6 February authorised PrEP only for pregnant or breastfeeding women.
Services for key populations have been funded extensively by PEPFAR in sub-Saharan Africa. Modelling shows that stopping PrEP for key populations could increase HIV acquisition by up to 30% in female sex workers, 20% in men who have sex with men and transgender women, and 15% in people who inject drugs.
Another model found that the initial 90-day pause in PEPFAR funding will lead to 100,000 lives lost and 130,000 perinatal HIV transmissions. "There is no scenario in which we will not be treating millions and millions of people for decades to come," Beyrer said.
He concluded by reminding delegates that President George W. Bush argued for PEPFAR by quoting from the Old Testament book of Deuteronomy: “I have set before you life and death. Therefore, choose life.”
PEPFAR study shows deadly impact of stopping children's HIV treatment
Nearly one in five HIV-positive children under the age of one who experienced treatment interruptions in 2024 subsequently died, according to a large-scale review presented at CROI.
The findings highlight the importance of maintaining continuity of care for young children with HIV, who are especially vulnerable to rapid progression of HIV disease. Although the study was designed to collect data on engagement in PEPFAR programmes over time, the findings starkly illustrate the risks associated with freezing funding of paediatric treatment programmes.
Researchers analysed data from over half a million children receiving HIV treatment through US-funded PEPFAR programmes in 53 countries. The study identified 21,325 children who experienced a treatment interruption, defined as gaps in clinical contact or delays in medication pick-up lasting more than 28 days.
Mortality after treatment interruption was highest among the youngest children, affecting up to 19.6% of infants under one year old, and up to 10.2% of children under five who interrupted treatment. Where cause of death was recorded (in only 22% of cases), over half were HIV-related.
For infants under one, treatment interruptions usually happened in the first three months, while older children typically continued treatment for at least six months before an interruption.
Since early 2022, the number of unexplained treatment interruptions has consistently exceeded the number of children returning to care after interruptions. This highlights the challenge of bringing children back to care once they have interrupted treatment, commented Michelle Yang, presenting the study.
Two more possible HIV cures after stem cell transplants
Two more people appear to be free of HIV after receiving stem cell transplants to treat blood cancers, according to reports presented at the conference. If the men remain in remission, they will be the ninth and tenth cases of functional cure after this procedure.
The ‘Chicago patient’, a 67-year-old man, had been living with HIV for 14 years when he was diagnosed with acute myeloid leukaemia. He received stem cells from a donor with the double CCR5-delta-32 mutation, which disables a receptor that most strains of HIV use to enter cells. When he first stopped antiretroviral treatment 15 months after the transplant, his viral load quickly rebounded, but he has now been in remission for 10 months after discontinuing medication a second time.
Interestingly, during the viral rebound, HIV remained undetectable in blood cells derived from the donor. Dr Paul Rubinstein of the University of Illinois at Chicago Medical Center explained that this suggests the resurgent virus came from a residual reservoir of cells infected prior to the transplant, while his new immune cells "truly were protected."
This is the first known case of sustained remission after viral rebound during an initial treatment interruption following a stem cell transplant. It suggests that early rebound does not rule out the possibility of a functional cure.
The second case, the ‘Oslo patient’, is a 58-year-old man who had been living with HIV for 14 years before being diagnosed with myelodysplastic syndrome. He received a stem cell transplant from a brother with the double CCR5-delta-32 mutation. After the transplant, he developed severe graft-versus-host disease, which was treated with the immunosuppressive drug ruxolitinib. Two years after stopping antiretrovirals, his viral load remains undetectable with no intact HIV DNA found in his blood or gut.
"Every case is important to build the knowledge about how cure can be achieved," said Dr Marius Trøseid of Oslo University Hospital. "It's important now to compare all these cases to try to find similarities... to see if we can find some things in common that could be used in future cure studies."
Researchers are still trying to determine the key factors in successful cases, which may include the CCR5 mutation status, conditioning therapy intensity, presence of graft-versus-host disease, and effects of specific immunosuppressive drugs.
"So far, there has been a lot of focus on the CCR5 mutation, but I think after the Geneva patient, there is now more focus on reducing the reservoir," Trøseid said.
Correction: This article was amended on 18 March 2025. The two new people possibly cured are the ninth and tenth cases of functional cure, rather than eighth and ninth.
Lenacapavir plus broadly neutralising antibodies could be twice-yearly HIV treatment
Two broadly neutralising antibodies (bnAbs), teropavimab and zinlirvimab, might be good partners for lenacapavir as HIV treatment, with each agent taken every six months, according to data from a phase II study presented at CROI.
Findings from the study, presented by Dr Onyema Ogbuagu of Yale University, suggest that combining lenacapavir (Sunlenca) with these two bnAbs could enable a twice-yearly treatment regimen. The trial showed that the lenacapavir / teropavimab / zinlirvimab (LTZ) regimen maintained viral suppression in 96% of participants over six months.
The trial enrolled 80 people with well-controlled HIV who were highly susceptible to the two bnAbs used. Participants either continued daily oral antiretroviral therapy or switched to six-monthly subcutaneous injections of lenacapavir and intravenous infusions of teropavimab and zinlirvimab.
After 26 weeks, both groups had comparable rates of viral suppression. Lenacapavir, teropavimab and zinlirvimab remained well above therapeutic levels over time. The regimen was well tolerated, with the main adverse event being injection site reactions.
One participant in the LTZ group experienced virological failure, apparently due to low levels of lenacapavir. They developed resistance to lenacapavir and loss of susceptibility to zinlirvimab.
Twice-yearly LTZ is a “huge advance” and is “the longest-acting complete regimen in advanced development,” said Dr Ogbuago. The study is ongoing, with a 52-week follow-up planned.
Dual antibodies keep HIV under control after stopping early ART
Two studies presented at CROI demonstrated the potential of broadly neutralising antibodies (bnAbs) to suppress HIV for prolonged periods without antiretroviral therapy (ART).
The RIO study enrolled 68 cisgender men in the UK and Denmark who had begun ART shortly after HIV infection. Participants received infusions of two long-acting antibodies (3BNC117 and 10-1074) or a placebo before stopping ART.
At week 20, 55% of antibody recipients maintained viral suppression (below 1000 copies/ml), compared to just 9% in the placebo group. At this point, participants who were still virally suppressed were given another shot of the two antibodies (or of the placebo) and continued without ART.
Remarkably, 39% of antibody recipients remained off ART at 72 weeks, with seven participants showing no detectable virus for over two years. Antibody levels had dropped to sub-therapeutic ranges by week 48, suggesting a “vaccine-like effect” had enhanced immune control. T-cell responses strengthened even without significant viral antigen exposure, indicating the antibodies primed the immune system beyond mere neutralisation.
In contrast, the FRESH cohort focused on 20 young women in KwaZulu-Natal, South Africa, who had been diagnosed during acute infection and had immediately started antiretroviral treatment. All participants received antibodies VRC07-523 and CAP256V2 alongside vesatolimod, an immune-boosting drug. ART was paused five weeks after infusion.
While most participants rebounded within six months, four of the 20 participants have maintained either undetectable viral loads (in two cases), or viral loads that have never risen above 2000 (in the other two), now for a median of 1.5 years.
The study shows that it is possible to conduct sophisticated cure research in a lower-income African setting, and for bnAb interventions to be active against HIV subtype C, which is prevalent in southern Africa.
Sign up for aidsmap bulletins
This is the first of our three summary news bulletins from CROI 2025. The next one will be sent on Monday 17 March and then the final one on Friday 21 March.
If you'd like to receive these bulletins as emails, and any future bulletins, sign up at www.aidsmap.com/subscribe-email-bulletins