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IAS 2025 Retrospective
Hope in the Face of Hardship: IAS 2025

Released: August 05, 2025

Jürgen K. Rockstroh
Jürgen K. Rockstroh, MD
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Key Takeaways
  • Funding cuts to HIV programs pose severe risks to the global HIV response.
  • Advancements in long-acting HIV treatment and prevention hold great promise for people who experience challenges adhering to daily oral medication.
  • In the era of ART simplification and long-acting therapy, considerations for hepatitis B must play a role in treatment decision-making.

The 13th International AIDS Society (IAS) Conference on HIV-Science, which took place July 13-17, 2025 in Kigali, Rwanda, was characterized by exciting scientific breakthroughs, but also serious discussions around the ongoing HIV funding crisis that threatens to reverse decades of progress in the HIV response.

The Impact of Reduced Funding on HIV Prevention and Treatment
Interesting modeling studies that were presented at the meeting addressed the impact of funding cuts in prevention, as well as in antiviral treatment.

A study from the University of Bristol explored the impact of cutting pre-exposure prophylaxis (PrEP) funding for key populations in sub-Saharan Africa. Investigators noted that in 2024, more than 700,000 people, including 200,000 individuals from key populations, including people who inject drugs, female sex workers, transgender women, and men who have sex with men, across 28 sub-Saharan African countries, were receiving PrEP through PEPFAR funding. The removal of PEPFAR-funded PrEP over 1 year was estimated to lead to nearly 7000 additional new HIV infections, with 85% of these occurring in key populations. I think the rate of new infections among key populations might have been even higher, were it not for currently low PrEP coverage among these groups altogether. Ultimately, the goal should not only be maintenance of current PrEP services, but expanding access to PrEP globally.

A second modeling study investigated the impact of global funding cuts from 2025 onward by using 26 existing, country-validated HIV models, representing up to 50% of people living with HIV worldwide. Globally, 49% of all reported international aid and 54% of reported PEPFAR funding are allocated to these countries. The discontinuation of PEPFAR, plus the anticipated cuts from other international donors, could lead to 4.4-10.8 million additional HIV infections, depending on each country’s mitigation efforts and recovery. Investigators also anticipated 770.000-2.9 million additional HIV-related deaths.

Although theoretical, these modeling studies are instrumental in demonstrating how financial cuts can shape the future course of the HIV epidemic. The data clearly advocate for maintaining funding levels to make sure that the international goal of preventing new HIV infections and AIDS cases can be reached.

New Additions to the HIV Treatment and Prevention Toolbox
Fortunately, the discussion on funding cuts was contrasted with great scientific breakthroughs, in particular regarding the growing toolbox of long-acting (LA) treatment options for prevention as well as HIV treatment. Following exciting data around LA injectable lenacapavir and cabotegravir for HIV prevention, investigators presented a new, once monthly oral PrEP pill, MK-8527. Results from a phase II study demonstrated a good safety profile, supporting advancement of MK-8527 into phase III trials in Africa. However, the big question looming behind these promising results is always how these new drugs will be implemented and funded, particularly in resource-limited settings.

With regard to HIV LA antiviral treatment, 1 of the most important studies presented at this year’s IAS meeting was the IMPALA Study, a multicenter, open-label, noninferiority phase IIIb trial from Uganda, Kenya, and South Africa comparing the efficacy of LA cabotegravir and rilpivirine (LA CAB + RPV) vs maintaining an oral regimen with 2 nucleos(t)ide reverse-transcriptase inhibitors plus dolutegravir in adults with poorly controlled HIV (N = 540), defined as HIV-1 RNA >1000 copies/mL in prior 2 years despite antiretroviral therapy (ART), history of loss to follow-up, or unlinked to HIV care for ≥3 months since HIV diagnosis. At Week 48, an impressive 91% of participants on LA CAB + RPV achieved undetectable HIV-1 RNA (the study’s primary endpoint), compared to 89% of participants on continuous oral ART. Of note, some of the 5 individuals with confirmed virologic failure on LA CAB + RPV already showed baseline nonnucleoside reverse-transcriptase inhibitor resistance, which may have contributed to developing virologic failure. There were no discontinuations due to injection-site reactions, and there was a clear preference for LA ART among participants who switched to LA CAB + RPV (94%). These results emphasize that LA treatments should be added to the treatment armamentarium in Africa and appear to work even in individuals with adherence challenges.

Considerations for HBV in the Context of HIV Care
With the current developments in LA ART and expansion of 2-drug regimens, there are now increasingly ART strategies that do not contain any active hepatitis B antivirals. Clearly, patients with chronic HBV should not receive such treatments and should instead stay on a tenofovir-containing ART regimen. Even individuals with completely negative HBV serology (negative anti-HBs antibody, negative anti-HBc antibody) still remain at risk of acquiring hepatitis B under tenofovir-free regimens and therefore should be vaccinated for HBV as a priority. Indeed, in the IMPALA study, 1 individual from the LA CAB + RPV arm developed an acute HBV infection. Overall, only 7.8% of the participants in the IMPALA study showed HBV vaccine–mediated immunity at baseline. This is a strong call for increasing HBV vaccination in individuals switching to tenofovir-free regimens.

Another important question is what happens to individuals who only have positive anti-HBc antibodies, but no anti-HBs titer. These patients were not included in the IMPALA study, but recent reports from other trials indicate that after switching to LA CAB + RPV therapy there is a risk of low-level HBV viremia. Fortunately, so far, no clinically relevant hepatic decompensation or HBV reactivation with reemergence of HBs-antigen has been reported in this particular subgroup. However, I think there is a clear need for better HBV-monitoring in these individuals, which may be difficult to implement in resource-limited settings.

Your Thoughts
What abstracts did you find the most impactful from IAS 2025? Do you plan on making any changes to your practice based on these new data? If so, what changes? Leave a comment to join the discussion!

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