AIDS 2026: PrEP efficacy depends on adherence not biology – PrEP access depends on politics
18 August 2026. Related: Conference reports, HIV prevention and transmission, Intl AIDS 26th Rio 2026.
Simon Collins, HIV i-Base
One of the important plenary sessions at AIDS 2026 was on the future of HIV prevention and included an excellent review on PrEP efficacy by Raphael Landovitz from UCLA. [1]
The research timeline covered results from iPrEX and other early studies using oral TDF/FTC (using daily and on-demand 2:1:1 dosing), oral TAF/FTC, injectable formulations of CAB-LA and lenacapavir, and an exciting PrEP pipeline.
The talk also focussed on the political blocks to access following cuts to USAID and PEPFAR funding, given that science has overwhelmingly proven PrEP efficacy.
In 2025, the $19 billion cuts to the US NIH terminated more than 750 grants including $643 million research grants and closed 113 active clinical trials, more than half of which were in HIV. As a result, both new PrEP initiations and the numbers of people retained on PrEP fell by 40% compared to 2024 in many of the countries with the highest rates of new HIV infections.
The focus on science though was also important for challenging years of research that led to different prescribing recommendations for women. Instead, the talk explained “the part of the story we told badly the first time”.
Low efficacy in some oral PrEP studies – especially the FEM-PREP and VOICE studies – was originally thought to be due to biological differences of poor drug absorption in vaginal tissue. More recent research however, shows that results from RCTs are more accurately explained by good or bad adherence: “The signal was never about biology, it was about adherence … The evidence was there the whole time, we just had to read it clearly”.
This link to adherence was clearly shown for TDF/TFC in MSM and transgender women in the i-PrEX in 2012 (Anderson et al) and in observational studies in women (Marrazzo et al) in 2024 – with >90% efficacy reported in both men and women when adherence involved 4 or more pills a week.
Adherence data using daily oral TAF/FTC also correlated with high efficacy in the DISCOVER and PURPOSE-1 trials. Notably, PURPOSE-1 produced 89% efficacy in women who took only two or more pills a week. These results informed the ongoing French/Thai SimpPrEP study in MSM and transgender women that only uses 1:1 dosing – only one dose of F/TAF before and another after sex. Results are expected within a year. Although not explicitly stated in the talk, pharmacokinetics explains these adherence differences: TAF achieves significantly higher drug levels in PBMCs and significantly lower levels in plasma, compared to TDF, despite using a lower dose.
Together these analyses led to the recommendations in the 2025 UK PrEP guidelines, later supported by EACS, that event-based dosing can be used for receptive vaginal sex. Rather than 2:1:1 dosing, the guidelines cautiously suggested 2:7 dosing, but also recognised fewer than seven post-sex daily doses might easily be just as effective (and other researchers have proposed 2:1:1:1).
But Landovitz also went further, while noting the preference for data from RCTs, he recognised that “the insights into PK/PD in PBMCs and large observational datasets are increasingly driving us to congruence and we may soon be seeing recommendations to harmonise 2:1:1 dosing across populations”.
This is an important conclusion, given that for all the astonishing efficacy of injectable PrEP, oral PrEP is likely to remain easier to access and cheaper to afford in many countries for at least the next few years.
Other issues covered in the talk included (i) the use of counterfactual study designs to show efficacy in future PrEP studies (estimating expected incidence as a control), and (ii) to defer to local/national guidelines for the choice of HIV testing to identify incident infections (when the antiviral impact of long-acting PrEP complicates early diagnosis). The letter included a call for better point-of-care HIV diagnostics, noting how quickly these were developed for COVID.
Finally, a review of the PrEP pipeline included once-monthly oral alimatravir (MK-8527) that is still in pngoing phase 3 studies, new formulations of annual lenacapavir and 4-monthly cabotegravir injections and weekly oral lenacapavir, already submitted to the FDA.
Results from a phase 2 rectal tenofovir douche study are also expected within 6 months and earlier phase studies include TAF/elvitegravir inserts with and without doxycycline.
In concluding, and returning to the importance of politics, even the exciting PrEP pipeline was referred to as less important than moral questions about government programming, political will and affordable pricing to enable widespread access.
comment
This plenary talk was important for clearly stating that the efficacy of oral PrEP is not linked drug levels in genital tissue, and therefore dosing recommendations do not need to be different due to biology and sex.
However, the differences between TDF and TAF show that pharmacokinetics is still essential to explain PrEP efficacy and adherence. TAF results in roughly 90% lower levels in blood plasma than TDF but 4-7 times higher levels in PBMCs.
Although AIDS 2026 was dominated by access to injectable CAB-LA and lenacapavir, their superior efficacy compared to oral PrEP was driven by easier adherence.
Although still dependent on upcoming clinical results, it is also possible that longer-acting oral PrEP with once-monthly oral alimatravir (MK-8527) or potentially once-weekly oral lenacapavir, might balance some of these differences, especially if lower pricing makes long-acting oral PrEP easier to access. [4]
References
- Raphael Landovitz. PrEP 2026: State of the ART: retitled to: PrEP Works: the challenge is no longer scientific. Plenary session PL02. https://programme.aids2026.org/Programme/Session/6128 (programme)
https://conference.aids2026.org/media-342-the-future-of-hiv-prevention (webcast) - Why the new HIV PrEP guidelines from the UK are so exciting (2025). HTB (2 July 2025).
https://i-base.info/htb/51432 - Merck announces alimatravir access programme ahead of AIDS 2026. HTB (24 July 2026).
https://i-base.info/htb/54297