Does six-monthly PrEP have a future following the collapse of global HIV funding?
A new HIV prevention tool requiring just two injections per year offers significant promise for reducing infections, but its roll-out faces major obstacles as global funding streams collapse. Lenacapavir, described as having "transformational potential" by Carolyn Amole of the Clinton Health Access Initiative at the 13th International AIDS Society Conference on HIV Science (IAS 2025) in Kigali, Rwanda, arrives at a time when traditional funding sources are disappearing.
The timing is particularly challenging. The Trump administration's radical cuts to PEPFAR, the global health programme that funded over 90% of PrEP users worldwide, have removed the main source of investment just as this breakthrough becomes available. As advocate Yvette Raphael put it: "Science is giving us powerful tools, but we don't have powerful money."
Despite these challenges, there are some promising developments. The World Health Organization released guidelines supporting lenacapavir for PrEP, and the Global Fund announced a deal potentially allowing two million people in low- and middle-income countries to access the drug by early 2026. However, this falls far short of what's needed to make a significant dent in the epidemic.
The experience with cabotegravir, a two-monthly injectable PrEP, illustrates the challenges ahead. Despite proving highly effective in 2020, only 28,000 people have ever used it, with over half in the United States. PEPFAR's ambitious African roll-out plans were already falling short when funding was cut in February, leaving programmes disrupted and raising ethical concerns about drug resistance for people already enrolled.
The path to affordable generic versions of lenacapavir offers more hope. Gilead signed licensing agreements with six generic manufacturers in October, and experts expect two companies to be ready to supply lenacapavir by early 2027. Multiple manufacturers competing could bring prices down significantly, potentially making generic lenacapavir available at a price competitive with oral PrEP.
But the current funding reality is harsh. Under the Global Fund-Gilead deal, countries must contribute US$60 per person annually from their already stretched allocations, with total costs around $100 per person compared to $25-40 for oral PrEP. This means only about nine countries can begin introduction, and only for limited populations.
While the data show strong demand for long-acting options, preferences vary between individuals. But not all options may be provided, as Professor Saiqa Mullick noted: "We need to balance choice with pragmatism; right now we are sitting with a couple of products that are unaffordable to most governments."
African health officials are being urged to make stronger investment cases to their finance ministries. Professor Lloyd Mulenga of the Zambia Ministry of Health stressed: "When it comes to budgeting, you prioritise what you think are game changers to fight public health challenges. If you don't do that, the politicians are not even going to listen to you."
Innovative approaches to PrEP delivery are emerging as essential to future sustainability. Health policy advocates argue that current provision is overly medicalised, with Imelda Mahaka of Pangaea Zimbabwe noting: "It's odd that people think it's OK to flood health facilities with people who are well." There's growing support for local facilities staffed with peer navigators and community champions instead of nurses – an approach that is not only more cost-effective but also enables programmes to reach scale more effectively.
The focus is shifting towards integrating PrEP into broader health services. Rather than standalone programmes, experts advocate for "bundling" PrEP into services users may already need – such as combining HIV prevention for young women with contraception, STI services, and pregnancy care.
The challenge now is translating these innovative approaches into scalable programmes that can fill the gap left by PEPFAR cuts.
- Read the news story about lenacapavir in full on aidsmap.com
- Read the news story about PrEP delivery in full on aidsmap.com
HIV integration sparks fierce debate as funding cuts bite
IAS 2025 saw heated debate over HIV service integration, with communities, advocates and health officials deeply divided on whether merging HIV care into general health services represents progress or a dangerous step backwards.
Integration – moving HIV services from specialised clinics into primary health care – has emerged as the go-to solution for countries facing US funding cuts. For example, Uganda's Ministry of Health issued a circular in February 2025 to remove standalone HIV clinics. The World Health Organization frames integration as delivering comprehensive health services throughout a person's life course, rather than the 'vertical' disease-specific programmes that have dominated HIV care.
However, fierce opposition came from community activists who see integration as a threat disguised as efficiency. "Integration is not the solution," declared advocate Yvette Raphael during a protest at the opening ceremony of the conference. "Without decriminalisation, accountability and the funding needed, integration will be a death sentence for us."
The concerns run deep. Key populations – gay and bisexual men, transgender people, sex workers, and people who use drugs – often require specialised, confidential services that build trust. Many had deliberately moved away from government facilities to community-led mobile clinics and drop-in centres to avoid criminalisation and hostile treatment.
Kenyan HIV advocate Patricia Asero highlighted the gap between rhetoric and reality: "What they are calling integration is just dispensing of HIV drugs," she said, arguing for true holistic care that addresses patients' multiple health needs simultaneously rather than simply relocating HIV medication distribution.
Yet examples from south-east Asia showed integration being implemented with attention to equity concerns. In Vietnam, social health insurance coverage among people with HIV reached 95% after the government funded community organisation outreach and waived premiums for vulnerable groups. Thailand's "social contracting" model reimburses community organisations per service.
The consensus? Integration can work, but only with genuine community leadership, adequate resources, decriminalisation, and an equity focus that doesn't sacrifice quality for efficiency.
US funding cuts cause immediate drops in HIV testing and treatment
Cuts in US funding for HIV programmes are already causing dramatic declines in testing and treatment across multiple countries, with research presented at IAS 2025 projecting devastating long-term consequences for the global HIV response.
Following the US government's pause in foreign assistance through USAID on 21 January 2025, thousands of HIV testing counsellors and clinic staff were laid off, and vital medications became stranded in warehouses. Although a limited waiver was granted for PEPFAR treatment services, this has not prevented significant service disruptions.
In Mozambique, where PEPFAR provided around two-thirds of HIV programme funding, the impact has been severe. Dr Dorlim Moiana Uetela presented data showing over 15,000 fewer people started antiretroviral treatment between February and May 2025 compared to the same period in 2024 – a 14% reduction. Viral load testing plummeted by 38% in adults and 44% in children, whilst viral suppression rates fell by 33% in adults and 43% in children. Treatment interruptions increased by 39% between April and May.
Using mathematical modelling, researchers estimated these disruptions would lead to 83,000 additional HIV infections by 2030 – a 15% increase – and 14,000 extra deaths, representing a 10% rise in HIV-related mortality.
In Johannesburg, South Africa, the Anova Health Institute reported substantial reductions between the first quarters of 2024 and 2025. HIV testing dropped 8.5%, HIV diagnoses fell 31%, and treatment initiation declined 30%. Researchers attributed these declines to the loss of healthcare workers providing counselling and community-based testing.
The most alarming findings came from global modelling covering 26 low- and middle-income countries that account for up to 50% of people living with HIV worldwide and which receive 49% of all global HIV aid. The analysis is particularly significant because it took account not only of the US cuts but also reductions by other major donors – the UK and France anticipate 40% cuts in foreign assistance by 2026, whilst the Netherlands will reduce assistance by 70%.
The researchers modelled three scenarios. Under a moderate scenario where prevention and community testing funding is cut by 24% by 2026 (whilst treatment services are sustained by domestic funding), they projected 71,500 to 1.7 million additional infections and 5000 to 61,000 extra deaths by 2030, depending on mitigation success. However, if PEPFAR funding were completely discontinued alongside the 24% cuts, the consequences would be catastrophic: 4.4 to 10.8 million new infections and 770,000 to 2.9 million additional deaths.
The impact would disproportionately affect vulnerable populations. Key populations would face HIV infection rates 30-60% higher than other groups outside Africa. Children would be particularly vulnerable – if PEPFAR funding ended, an estimated 880,000 new HIV infections and 120,000 deaths would occur among children in low- and middle-income countries between 2025 and 2030.
Antibody combination shows promise in the search for an HIV cure
A study has shown that more than half of people with HIV who received specialised antibodies combined with an immune-stimulating drug were able to maintain low or suppressed viral loads during treatment interruption, representing a potential step towards functional HIV cure strategies. One participant has remained off antiretroviral therapy (ART) for over 30 months.
Professor Marina Caskey of Rockefeller University presented findings from a clinical trial involving 28 people with chronic HIV infection who were stable on ART. Participants received infusions of two broadly neutralising antibodies (bnAbs) – 3BNC117-LS and 10-1074-LS – followed by up to eight injections of N-803 (Anktiva), an immune-modulating drug originally developed for bladder cancer. Two days after receiving the antibodies, participants temporarily stopped their HIV medications under careful medical supervision.
The results were encouraging. Among 24 participants who stopped ART, 58% did not need to restart treatment at six months, nearly a third remained off therapy after a year, and one person continues without antiretrovirals after more than 30 months. "So far, what we are most excited about is that we see among participants with delayed rebound that they show different patterns of rebound dynamics, and some of these participants maintain low level viremia for a prolonged period of time," Caskey explained.
The combination was generally safe and well-tolerated, with mostly mild side effects including injection site reactions that diminished over time. However, the study had limitations – there was no control group receiving antibodies alone, making it difficult to determine N-803's specific contribution. The findings suggest this approach could advance functional HIV cure research, though more research is needed to understand the underlying mechanisms and optimise treatment protocols.
Conflicts and humanitarian crises create new HIV vulnerabilities
Humanitarian crises and armed conflicts are creating dangerous new vulnerabilities for people living with HIV, according to presentations at IAS 2025 that highlighted both challenges and innovative solutions.
Dr Daniela Garone from Médecins Sans Frontières (MSF) revealed the scale of the problem: an estimated one in every 14 people living in humanitarian contexts have HIV, including 157,000 children and 162,000 adolescents. Access to treatment is critically limited, with 43% of pregnant women and 79% of adolescents lacking access to antiretroviral therapy (ART).
MSF's work across 14 countries with armed conflict shows how displacement and violence exacerbate HIV vulnerabilities. In the Nord Kivu region of Democratic Republic of Congo, HIV prevalence reaches 3% compared to 0.7% nationally, with only 18% achieving viral suppression. However, community-based approaches are proving effective: in the Central African Republic's Haut-Mbomou region, community ART groups reduced the risk of being lost to follow-up by four times and halved the death risk among people with HIV.
Perhaps most encouraging were findings from Haiti presented by Dr Darwin Dorestan of Georgetown University. With around one million people internally displaced by ongoing violence and instability, Haiti developed a Drug Dispensing Points (DDP) model that created nationwide 'pharmacy chains' in strategic areas. Trained community workers, equipped with digital tools, provided ART refills at 57 sites including pharmacies, community centres, and notably, a voodoo temple where priestesses delivered HIV services.
The results were remarkable: over 11,000 ART refills between 2020 and 2024 achieved a 98% viral suppression rate. More than 88% of pick-ups occurred outside people's usual districts, demonstrating the model's effectiveness for displaced populations. "It is possible to make a difference and to develop a resilient HIV response through this model," Dorestan concluded. "Put the community at the wheel – even in the most fragile and dangerous environments."
The presentations underscore how community-centred, flexible approaches can maintain HIV care even in the world's most challenging circumstances.
Children born with HIV show persistent inflammation despite successful treatment
Two studies presented at IAS 2025 revealed that children born with HIV carry persistent markers of chronic immune activation that could lead to premature heart disease, even when they achieve full viral suppression through antiretroviral therapy (ART).
South African researchers compared 68 children with HIV to 121 HIV-negative children from similar backgrounds. Despite having started ART before three months of age and 93% viral suppression rates, the HIV-positive children showed elevated levels of six inflammatory biomarkers. C-reactive protein was 76% higher and interleukin-6 was 15% higher – both linked to cardiovascular risk. Vascular endothelial growth factor, associated with blood vessel damage, was 37% higher.
The inflammation appeared to worsen with age, particularly markers of gut inflammation in teenagers aged 13-16. Boys showed different patterns from girls, with higher levels of proteins affecting fat and glucose metabolism.
A Canadian study of 225 children found that those starting treatment before six months had significantly smaller HIV reservoirs and lower inflammation levels. Children treated earliest averaged just 12.6 HIV DNA copies per million cells, compared to 56-79 copies in later-treated groups.
Both studies suggest that children born with HIV benefit most from starting treatment as early as possible and achieving rapid viral suppression.
Stepping into the AI-driven future of HIV services
Experts at the conference discussed the transformative potential – and challenges – of artificial intelligence (AI) in HIV prevention and care. Community advocate Solange Baptiste underlined AI’s ability to rapidly analyse large-scale health data to identify patterns, manage supply chains, and personalise care. She stressed the importance of using big data to generate intelligence that improves decisions, outcomes and equity.
But she cautioned that without community-centred data, AI risks amplifying existing inequalities. “If we don’t include the lived experience, AI will reproduce the blind spots,” she said. “So what we have is something nice and fancy and shiny and new that’s just reproducing the inequities we see – and doing it much faster.”
Rouella Mendonca of Audere introduced Aimee, a WhatsApp-based chatbot co-designed with South African adolescent girls and young women. Within months, Aimee reached over 1500 active monthly users, exchanging more than 30,000 messages. Nearly 40% of users return each month, showing strong engagement and trust.
Aimee is presented as “your personal AI bestie, right at your fingertips… ready to chat anytime about the stuff you don’t want to Google or ask out loud”. She can provide information and advice on PrEP, pregnancy, relationships, HIV and gender-based violence.
Aimee builds trust through empathic responses, sentiment detection, progressive disclosure and active listening. Building trust takes time – many users raise sensitive topics after coming back to Aimee a second or third time. Users speak to Aimee about topics such as gender-based violence and relationships much more frequently than they do to nurses.
Sebastian Villanueva Guzman of Polytechnique Montréal presented MARVIN, a Canadian chatbot that assists people living with HIV in self-management. In its early iteration, MARVIN struggled with messages expressing suicidal ideation and with insults.
MARVIN was adjusted to ensure that he could recognise and respond appropriately – for example, providing emergency contact information for any messages discussing self-harm ideation and guidance for users on avoiding insulting language.
Next steps include being trained to detect more signs of psychological distress, such as markers of depression and anxiety, which may enable him to become a more well-rounded digital companion for people with HIV.