The need for collaboration and community-inclusive practices to advance HIV prevention efforts in the face of significant funding constraints was a focal point of those who spoke during a session at the International AIDS Society meeting in Kigali, Rwanda.
The session, co-hosted by the Bill & Melinda Gates Foundation, Gilead, Merck, and the Reproductive Health Institute, gathered researchers, advocates and community leaders to address adapting to a changing funding environment for research of HIV prevention. They addressed the evolving landscape of HIV prevention, including oral HIV preexposure prophylaxis (PrEP), HIV vaccines and broadly neutralizing antibodies (bnAbs), a newer area of research.
They urged attendees of the need to continue with research of HIV prevention despite funding from the United States that is being pulled back. A concern of speakers was the recent termination of 191 HIV-specific grants by the U.S. National Institutes of Health (NIH), which slashed more than $200 million in funding — disrupting early-stage research, behavioral interventions, and vaccine development.
Nyaradzo Mavis Mgodi, MBChB
“We saw that $99 million was cut from HIV prevention, including the work that I do in HIV, biomedical products, behavioral interventions and access barriers and key populations were not spared,” Nyaradzo Mavis Mgodi, MB.ChB., biomedical HIV prevention methods, University of Zimbabwe Clinical Trials Research Centre, said during the session. “The cuts have adversely affected us all.”
Mgodi and other speakers presented key takeaways from the Future of HIV Prevention Clinical Trials Summit, which was held in June 2025 in Johannesburg, South Africa. At the heart of the discussions at the June Summit and at IAS was the urgent push for smarter, more agile clinical trials that keep the focus on community engagement. Speakers stressed the need for innovative trial designs that use modeling and artificial intelligence that can accelerate development without sacrificing inclusivity or scientific rigor.
Speakers also talked about the HIV prevention pipeline and recent results of trials. Despite the recent approval of lenacapavir as a twice-yearly PrEP, there is still a need for choice in HIV prevention. Developed by Gilead Sciences, lenacapavir (now with the brand name Yeztugo) was approved by the FDA on June 18 as both an oral tablet and as a subcutaneous injection.
“The context for HIV prevention research is rapidly evolving,” Grace Kumwenda, regional program manager at AVAC in Malawi, said during the session. “We are facing shifting epidemiology. Some populations are seeing lower incidence, and others remain quite underserved. At the same time, how do we design and prioritize research?”
Oral PrEP
Merck recently announced that it will begin phase 3 clinical trials of MK-8527, an investigational once-monthly oral for HIV PrEP. The EXPrESSIVE-11 trial will evaluate the safety and efficacy of MK-8527 in 16 countries and will begin enrolling in August 2025.
MK-8527 is a nucleoside reverse transcriptase translocation inhibitor (NRTTI), and in the trial it will be compared with emtricitabine/tenofovir disoproxil fumarate, which is available as a generic. A branded emtricitabine/tenofovir disoproxil fumarate is marketed as Truvada by Gilead.
A phase 2 trial of MK-8527 enrolled 350 participants with a low likelihood of HIV-1 exposure, who were randomized to one of three doses of MK-8527 or placebo once monthly for six months. In the trial, the rates of adverse events were similar among those in the MK-8527 arms and those in the placebo arm, and no clinically meaningful changes were seen in laboratory tests, including total lymphocyte and CD4 T-cell counts.
Rebeca Plank, M.D., senior principal scientist, clinical research at Merck, said during the IAS session that researchers carefully considered the comparator that would be used in EXPrESSIVE-11 trial, consulting community organizations and other stakeholders.
Originally, researchers considered using Vocabria (cabotegravir), an oral integrase strand transfer inhibitor (INST) that is taken daily when used as PrEP. But MK-8527 will be used monthly, and Plank said researchers were looking for direct comparison.
“This was done in consultation with various stakeholders from the beginning and even before the protocols really began to be drafted,” Plank said.
She also pointed out that the comparator was chosen before the approval of lenacapavir, a twice-yearly PrEP. Developed by Gilead Sciences, lenacapavir (now with the brand name Yeztugo) was approved by the FDA on June 18 as both an oral tablet and as a subcutaneous injection.
Vaccines
Despite many years of research, a vaccine using active immunization hasn’t been successfully developed because of biological and technical challenges of making an HIV vaccine. Mgodi said there have been some positive signals, especially with RV144. A Thailand study of RV144 conducted almost a decade ago demonstrated that the vaccine was safe and had a statistically significant decrease in HIV infection. But protective immunity appeared to wane, and the vaccine is not currently available.
Other studies have given a negative result because HIV is highly unstable.
Some, however, have questioned whether a vaccine is still needed because of the availability of long-acting PrEP such as lenacapavir. Mgodi made the case during her presentation that vaccines would add to the arsenal of HIV prevention.
“There are people who are not adherent to PrEP, and we know that many people who acquire HIV don’t perceive themselves to be at risk,” she said. “That’s one reason why we need a vaccine as an alternative to PrEP that is focused on specific populations, which really sometimes marginalizes others or stigmatizes others.”
She said that vaccines have the potential to prevent between 8.4 million and 19 million new HIV infections, depending on efficacy.
bnAbs
Research is continuing, however, on passive immunization with broadly neutralizing antibodies, or bnAbs, which are a type of antibody that can recognize and block different HIV strains. Organizations, such as IAVI, and groups funded by the National Institutes of Health (NIH), such as the Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), are conducting research in this area.
In May 2025, IAVI and Scripps Research released data from two separate phase 1 trials showing that a targeted vaccine strategy can successfully activate early immune responses relevant to HIV. The trials included nearly 80 participants from both North America and Africa, and the study was published in Science on May 15, 2025.
One of the trials tested a stepwise vaccination strategy, in which a priming dose and a distinct booster dose were given sequentially to guide the immune system through stages of antibody development. The second trial focused on the priming stage and showed that an initial vaccine dose could successfully activate the desired immune cells in African participants.
Commercial companies, such as ViiV Healthcare, are also developing bnAbs. In March 2025, ViiV released data from a phase 2b study that N6LS, a bNAb administered every four months, effectively maintained undetectable viral load when combined with Apretude, a long-acting cabotegravir. The study found that the combination kept viral levels suppressed in adults living with HIV who were already stable on treatment. It was also well tolerated by participants.