The global HIV response confronts its most severe funding crisis in decades following sweeping US government cuts in January, threatening to reverse remarkable progress towards ending the epidemic. Speaking at the 13th International AIDS Society Conference on HIV Science (IAS 2025) in Kigali, Rwanda, experts warned that recent advances – including promising new prevention tools – risk being overshadowed by resource shortfalls that could result in six million new HIV infections and four million additional AIDS-related deaths by 2030.

The 2025 UNAIDS Global Update revealed significant achievements prior to the arrival of the Trump administration in January: new HIV infections fell 40% since 2010 to 1.3 million, whilst AIDS-related deaths declined 54% to 630,000 cases. Sub-Saharan Africa, bearing half of all new infections, saw a 56% reduction in new cases since 2010, with life expectancy rising from 56.5 to 62.3 years over 14 years.

Winnie Byanyima, UNAIDS Executive Director, described this as "one of the most successful public health responses in history, saving more than 26 million lives." However, recent funding cuts threaten to derail this progress.

The crisis extends beyond PEPFAR cuts alone. Other major donors have gradually reduced contributions over time, weakening mechanisms such as the Global Fund. There has been encouraging progress towards self-reliance, with domestic contributions rising by 28% since 2010, outpacing the 12% growth in international HIV funding. However, 22 countries still rely heavily on external donor funding, many of them in Africa.

Professor Linda-Gail Bekker from the Desmond Tutu HIV Foundation delivered a stark assessment: "We no longer stand at a crossroads. We now find ourselves at a precipice." As principal investigator of the PURPOSE 1 trial demonstrating lenacapavir's 100% efficacy in preventing HIV among young African women, Bekker highlighted the cruel irony of having breakthrough prevention tools whilst facing resource constraints.

Prevention services have been particularly affected, with an estimated 2.5 million people losing access to oral PrEP this year. Injectable PrEP uptake remains disappointingly low at 25,000 users globally, whilst the dapivirine vaginal ring has only 2000 users.

Bekker called for building a "resilience bridge" through emergency planning, bridging funding, and novel financing mechanisms incorporating artificial intelligence and digital health innovations. She added: "It can't be done without community and the community needs resources and backing."

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DoxyPEP (doxycycline post-exposure prophylaxis), a promising antibiotic prevention method for sexually transmitted infections, faces growing concerns about drug resistance as it enters widespread clinical use. At IAS 2025, experts discussed the mounting challenges of implementing doxyPEP whilst managing the risk of creating antibiotic-resistant gonorrhoea strains.

DoxyPEP involves taking 200mg of doxycycline within 72 hours after sex and has proven highly effective against chlamydia and syphilis in trials with men who have sex with men and transgender women. However, its effectiveness against gonorrhoea varies significantly by region, with French trials showing reduced efficacy compared to American studies, likely due to higher background resistance levels.

Implementation approaches differ markedly between countries. In the US, San Francisco issued broad guidelines in 2022 extending recommendations beyond the highest-risk populations, while more recent Australian and European guidance takes a more cautious approach. The UK's first doxyPEP guidelines, released last month, focus specifically on syphilis prevention. In countries without guidance, informal use is growing.

For cisgender women, the picture remains uncertain. A Kenyan study found doxyPEP ineffective, largely due to inconsistent use, whilst Professor Elizabeth Bukusi of the Kenya Medical Research Institute is exploring directly observed therapy approaches. Young women in Africa face high STI risks and complications including pelvic inflammatory disease from chlamydia. As she noted, "when we delay guidelines, there are real consequences for women" and emphasised the need to involve young women in finding solutions that work for them.

Resistance concerns are materialising. A study published in The New England Journal of Medicine just before the conference revealed that extensively drug-resistant gonorrhoea is spreading across the United States. High-level tetracycline resistance among gonorrhoea isolates rose from under 10% in 2020 to over 30% by early 2024, with the highest rates in the northwest region, including Seattle – an early doxyPEP adopter.

Professor Jean-Michel Molina of Hôpital St Louis in Paris, who has led multiple STI prevention trials, emphasised the need for balance: "I think we can do better, but it is time to implement doxyPEP in people at risk. We need to be cautious: it's not for everyone."

The findings suggest that whilst doxyPEP remains valuable for preventing chlamydia and syphilis, its role in gonorrhoea prevention may be limited by resistance. Experts agreed that alternative approaches, including vaccine development, will be essential for tackling gonorrhoea. The challenge now lies in implementing doxyPEP responsibly whilst monitoring resistance patterns and developing next-generation prevention strategies.

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Rwanda – the host country for IAS 2025 – has emerged as a continental leader in HIV control, demonstrating how strong leadership and community-centred approaches can deliver exceptional results even in resource-limited settings. Speaking at the conference, the country's health officials outlined how Rwanda became one of only seven African nations to achieve the UNAIDS 95-95-95 targets.

Rwanda's HIV response has delivered remarkable outcomes among its 14 million population. Of the estimated 230,000 people living with HIV, 96% know their status, 98% are on treatment, and 98% are virally suppressed. Nearly 99% of HIV-positive pregnant women receive antiretroviral therapy, supporting elimination of mother-to-child transmission. In 2024, the country recorded just 3200 new HIV infections.

Dr Sabin Nsanzimana, Rwanda's Minister of Health, credited the success to comprehensive system-building: "We have been building from scratch through leadership, partnerships, community-led approaches, and cross-sector innovation. Together, we met the UNAIDS 95-95-95 targets ahead of schedule."

The country's approach emphasises accountability and surveillance through a nationwide medical record system enabling data sharing and continuous feedback to improve programme design. A hallmark of Rwanda's response is strong national co-ordination, with all HIV-related partnerships centrally managed to avoid duplication and optimise resource use.

Rwanda was among the first in the region to adopt ‘treat all’ guidelines in 2016, achieving the most rapid increase in rapid treatment initiation compared to neighbouring countries. Dr Kathryn Anastos from Women's Equity in Access to Care and Treatment (WE ACTx) highlighted interventions including mandatory patient education sessions, buddy systems for adherence support, and community health workers following up missed appointments.

Despite overall success, significant disparities remain among key populations. While national HIV prevalence is under 3%, it reaches 35% among female sex workers and 6% among men who have sex with men. PrEP retention rates vary considerably, with men who have sex with men achieving just under 60% retention compared to 40-50% in other groups.

In response to recent global funding cuts, Rwanda has prioritised essential programmes, delayed or restructured activities, and shifted training online whilst increasing domestic financing through the national treasury.

“We need to continue funding and financing our programmes, it is an investment, not a cost,” the minister concluded.

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Researchers have successfully engineered killer T-cells that can halve the number of HIV-infected cells capable of producing new virus, potentially marking a significant step towards an HIV cure. The laboratory study, presented at the conference, mimics the effect of an experimental vaccine that appeared to cure half of infected monkeys over a decade ago.

Professor J. Victor Garcia of the University of Birmingham, Alabama, and his team took T-cells from mice and modified them to recognise specific HIV components through a rare immune pathway involving HLA-E molecules. Unlike conventional immune responses that vary between individuals, HLA-E-restricted responses are virtually universal, making this approach potentially applicable across diverse populations and HIV strains.

The researchers expanded these engineered cells and infused them into humanised mice infected with HIV. Within two to three weeks, the engineered T-cells reduced viral loads in blood by 80% and showed similar reductions in tissue. The cells concentrated in bone marrow and lymph nodes – exactly where they needed to be – at levels 35 times higher than in untreated mice.

In a second experiment, four doses of HLA-E restricted CD8 cells were given weekly to mice already on antiretroviral therapy. Despite the mice being virally suppressed, the engineered cells nearly halved the amount of intact viral DNA capable of forming new viruses. This suggests the treatment could target the HIV reservoir – the hidden pool of infected cells that prevents current treatments from curing HIV.

"HLA-E based cell therapy, with its 'universal' nature, holds significant potential as a novel approach to curing HIV," Garcia commented. The findings have surprised HIV cure experts, with some noting they hadn't previously seen evidence that HLA-E restricted CD8 cells could reduce HIV levels in blood on their own.

While promising, the research remains in early laboratory stages, with human trials still needed to determine safety and effectiveness.

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