The state of PrEP worldwide and new strategies for uptake

Funding cuts decimated PrEP uptake worldwide 

Even before President Donald Trump issued executive orders last year that slashed many foreign-assistance programs, use of PrEP, especially in developing and resource-poor countries that depend on such aid, was seriously lagging. In the past year, PrEP use in many parts of the world has fallen off a cliff, according to Andrew Hill, PhD, of Liverpool University in the UK. At CROI 2026, Hill shared data showing that U.S. funding cuts reduced the number of people on PrEP by as much as 98% in some countries since 2024. He added an urgent warning: if funding is not restored, not only would the UNAIDS target of no more than 370,000 new cases of HIV a year not be met, there could be more than 1.4 million HIV acquisitions per year worldwide. 

Even the most effective methods of HIV prevention available today—injectable PrEP—has to reach a lot of people to have a significant effect on reducing HIV cases. That would require affordable mass distribution, he said, which is not happening. 

“PrEP is having little or no impact on HIV incidence in low- and middle-income countries,” Hill said.

He added that long-acting injectable PrEP, which could address adherence issues, though it is still cost-prohibitive in most countries, could be a game changer worldwide. He referred to two studies—PURPOSE 1 in African cisgender women and PURPOSE 2 in men who have sex with men (MSM) and trans people worldwide—to estimate the effect of injectable lenacapavir for PrEP (LEN) on the overall population. Hill said that, based on data from these two studies, LEN prevented one HIV acquisition for every 42 people who would otherwise have acquired HIV over the course of a year.

But few countries are achieving this rate of PrEP coverage, through oral or injectable: only Australia, Denmark and Norway are currently preventing at least one acquisition per 42 people, with the UK preventing an estimated acquisition per 40 people. African countries have fared the worst, even before PEPFAR cuts: In South Africa, for example, there was only one person on PrEP for every five new acquisitions before the cuts. In Zambia, the rate was one person on PrEP for every 14. After the U.S. global aid cuts, there are 28% fewer PrEP users in South Africa, despite governmental funding, and 58% fewer users in Zambia. In other countries PrEP use has gone from minimal to negligible. PrEP use in Uganda has fallen by 70%, Malawi by 75% and in Nigeria by 98%. By the raw numbers, Nigeria has gone from nearly 400,000 PrEP users in 2024 to only 7,000 in a year. 

It isn’t just PEPFAR cuts causing a drop in PrEP coverage, Hill pointed out. PrEP usage in Brazil, which hadn’t received U.S. funding, fell from approximately 170,000 to 101,000 between December 2024 and December 2025. India’s PrEP coverage still hasn’t gotten off the ground, with only 2,100 people using PrEP in the whole country, translating to approximately two users for every 100 HIV acquisitions. If these trends don’t reverse, Hill reported, global HIV infections in 2030—the target for Ending the Epidemic goals—will remain at 2022 levels.

Hill proposed several possible solutions, each with their own difficulties, without the restoration of U.S. funding (and that restoration is unlikely during the Trump administration). These funding workarounds, all with their own difficulties, including restricting PrEP to people who are most vulnerable in developing countries, such as sex workers, and making PrEP as cheaply as possible, utilizing generics. 

Right now, wider use of generics has the most promise: tenofivir is available in the U.S. at $35 per person per year. As for long-acting injectable PrEP, drugmaker ViiV Healthcare has agreed to license generic long-acting cabotegravir (CAB) for $180 a year in 90 countries, while Gilead has signed non-exclusive, royalty-free licensing agreements with six generic manufacturers to produce and supply lenacapavir for 120 lower-income countries. Last year Hill presented findings showing that the drug could be manufactured for about the same price as oral PrEP and still turn a profit for the company, provided that PrEP use scales up substantially. In addition to these methods, Hill recommended an HIV Protection Fund of $500 million a year, which he estimated would jump start the use of long-acting lenacapavir in low- and middle-income countries.

“We have achieved high coverage of ART [antiretroviral therapy] worldwide,” Hill said. “Now we need to do the same for PrEP.” 

New data show lenacapavir for PrEP highly effective and well-tolerated

Other presentations at CROI 2026 shared new longer-term data on long-acting PrEP in various populations, adding to the growing amount of evidence that injectable PrEP is highly effective at preventing HIV, provided that people can access it. 

Nkosiphile Ndlovu, MBChB, senior research clinician at Wits Reproductive Health and HIV Institute in South Africa, presented longer-term safety and efficacy data on twice-yearly subcutaneous lenacapavir (LEN) through the end of the randomized blinded phase of PURPOSE 1. LEN efficacy remained high for the trial’s population, young cisgender women, through the end of the randomized blinded phase, with 77 new HIV acquisitions in both oral PrEP arms, compared to only two new acquisitions in the LEN group. Ndlovu did not say, but it was speculated that the efficacy of LEN versus oral PrEP was due to adherence issues. 

LEN was also shown to be well-tolerated, with no new discontinuations due to side effects. 

Dr. Ndlovu emphasized the need for long-acting PrEP in young cisgender women, noting that, globally, nearly half of all new HIV cases in 2024 were among girls and women. In sub-Saharan Africa, girls and women accounted for nearly two-thirds of new HIV acquisitions. “These findings position twice-yearly subcutaneous LEN as a powerful, durable, low-burden HIV prevention option for one of the populations most urgently needing innovation,” she said. 

In the same session at CROI 2026, longer-term follow up data were presented from the end of the randomized PURPOSE 2 trial. Valeria Cantos Lucio, MD, a physician at Emory University in Atlanta, shared data from PURPOSE 2, an ongoing phase three clinical trial where participants, cisgender men and gender diverse people who have sex with men, were randomized to two groups receiving either subcutaneous LEN every 26 weeks or oral medication (the generic version of Truvada, emtricitabine plus tenofovir DF, or F/TDF). The longer-term data closely resemble earlier findings, with LEN remaining highly efficacious through the end of the randomized blinded phase, Dr. Lucio said. “Since the primary analysis, one new HIV acquisition occurred in the lenacapavir group for an overall total of three, and three new HIV acquisitions occurred in the F/TDF group for an overall total of 12,” she said. “This yields an HIV incidence rate of 0.11 per 100 person year in LEN group, and 0.92 per 100 person year in the F/TDF group.” 

As with the PURPOSE 1 results, there were no new discontinuations due to side effects. 

PrEP for postpartum women: more choices equal better adherence

Another presentation at CROI 2026 emphasized the need for more choices in how cisgender women get PrEP.  The “dynamic choice" HIV prevention model, which allows people to choose and switch between daily oral PrEP, post-exposure prophylaxis (PEP) and long-acting cabotegravir (CAB), has gotten attention in recent years. But there’s also a dynamic choice model for delivering PrEP as well, and it appears that many postpartum women appreciate the option of having fewer steps (no counseling needed) in getting PrEP. 

Dvora L. Joseph Davey, MPH, PhD, a professor at the University of California–Los Angeles, shared results of a study on dynamic choice, also called dynamic service delivery or DSD, in PrEP delivery and HIV testing for postpartum women. When offered the choice of rapid clinic pick-up of PrEP (and a choice in HIV testing), most women chose this option, and half switched their method of collecting PrEP. The study enrolled 266 women (132 in the dynamic choice arm and 134 in the counseling arm) who had discontinued PrEP or had poor adherence for more than three months while pregnant. Participants were mostly young—median age of 25—unmarried and sexually active. 

In the dynamic choice arm, 49% preferred rapid clinic pick-up of PrEP, versus 46% preferring home delivery and 7% choosing community pick-up. For HIV testing, 57% chose clinic-based rapid testing while 43% chose self-testing. Researchers found that dynamic choice improved PrEP continuation and adherence compared to biofeedback PrEP counseling, (58% continuation and adherence, versus 42% continuation and adherence, respectively) in the first three months. Overall, nearly half (45%) in the dynamic choice arm were PrEP adherent by the study’s endpoint. 

“Dynamic choice in PrEP delivery increased the odds of PrEP persistence, highlighting the need for choice in PrEP delivery and modalities,” Dr. Davey said. 

French study: Better PrEP outreach needed among foreign-born populations

Following up on the results from its first three years, published in 2022, the final results of a large French study that offered a choice of daily or event-driven (on-demand) oral PrEP were presented at CROI. 

The Prévenir Study, which ended in May 2025, enrolled over 3,200 people, most of them cisgender men who have sex with men (MSM), at 26 sites in the Paris region. Final results showed that both daily and on-demand oral PrEP (tenofovir disoproxil/emtricitabine) were safe and effective, according to presenter Jean-Michel Molina, MD, MPH, professor of Infectious Diseases at the University of Paris Cité and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals in Paris. 

“Enrolling mostly MSM, born in France, we had a very low HIV incidence, which was sustained over the eight years of follow up, a good safety profile with on-demand PrEP… and a significant reduction in Paris during the time of the study of HIV diagnosis among MSM born in France,” Dr. Molina said. 

But it was a different story for MSMs not born in France, many who came from Africa, and accounted for nearly one in six participants (17.5%). For the French-born majority, HIV cases fell by a third, but for participants born abroad, HIV acquisition increased by 73%, resulting in no significant change in HIV diagnoses among study participants, overall. These results led him to conclude that better outreach and PrEP education is needed to inform and protect vulnerable populations, including immigrants. 

Even with the high rate of new HIV cases among foreign-born Parisians, the overall annual HIV incidence for all study participants was very low: only 14 participants acquired HIV, for a rate of 0.11% annually. HIV incidence was double for people who primarily used PrEP on demand, but because there were so few HIV acquisitions, the difference was not statistically significant, he said. Nine of the 13 who acquired HIV were not taking PrEP, and the other four showed evidence of suboptimal adherence. People were likelier to switch to on-demand PrEP when they were having less sex, and on-demand users tended to be older.

Throughout the study, half of the participants were taking daily PrEP and half event-driven or on demand. However, participants were likely to switch between daily and on-demand, based on their lifestyle and perceived risk: nearly two-thirds of participants who started on daily PrEP changed to on-demand at least once; slightly more than half changed at least once from on-demand to daily. 

One disappointment: a goal of the Prévenir study, to lead to a 15% population reduction in HIV cases in the Paris region over eight years, was not met, he said. Population-level HIV incidence only fell by 2% during that time, even though the overall number of PrEP users in the region increased from a few hundred to more than 27,000.

Digging into study details, nearly all (99%) of Prévenir participants were MSM, 85% were white, and the average age was 36. Only a few participants (27) were heterosexual women or men and 14 were transgender women. Most (60%) had previously used PrEP.

Participants were divided into three arms: those who spent more than three-quarters of the study period on daily PrEP (38%), those who spent more than three-quarters of the time using on-demand PrEP (38%) and those who switched back and forth (23%). As to be expected with such a long study, of the many participants who dropped out, 66% of on-demand users, 60.5% of daily users, and 56% of switchers left the study. Other findings:

• Only a small percentage of discontinuations were due to side effects, and the only significant drug-related adverse events were gastrointestinal (experienced by 4.5% of on-demand users, and much less by daily users).
• There was a high annual incidence of gonorrhea and chlamydia (33% and 26% respectively), but a low rate of syphilis (1%).
• Hepatis C infections were high across all arms (61 in total or an annual incidence of 0.45%), attributed mostly to IV drug use.
• The number of sexual partners decreased by 23% among daily PrEP users and by 37% in switchers over eight years.
• The proportion of people who had receptive sex without a condom rose overall from 40% to 50% over eight years.