AIDS 2026: High efficacy continues in open label extensions to lenacapavir phase 3 PrEP studies

Simon Collins, HIV i-Base

On 21 July 2026, still almost a week before the AIDS 2026 conference even opens, the embargo was lifted early on seven key studies at an early virtual press conference.

This included results of two open label extension phases of the phase 3 PURPOSE-1 and -2 studies using 6-monthly injectable lenacapvir PrEP.

These large randomised studies continue to report extremely high efficacy after an additional year of follow-up. This included new data on participants who were not previously receiving lenacapavir but who had the chance to choose this option in an open-label extension (OLE) after the blinded randomised phase.

Uptake in both studies was high at over 95% of those eligible to join and no new safety concerns were reported in either study.

• No new infections were reported in during 4493 patient years of follow-up in the OLE phase of the PURPOSE 1 study in women in Uganda and South Africa. However, in the study overall there was one case of infection in the blinded lenacapavir arm. Adherence to injections was reported at 96%. [1]
• One new case of HIV transmission was reported during 2452 patient years of follow-up in the OLE in the PURPOSE 2 study in cisgender men and trans and non-binary people all who have sex with men enrolled in Argentina Brazil Mexico Peru South Africa Thailand and the US. The limited details on this case include that injections were on time but the drug levels are not yet available. Adherence was 96% and 92% at weeks 26 and 52, respectively.

Although it is important that both studies continue to show that HIV incidence was significantly lower with 6-monthly lenacapavir injections compared to oral PrEP, full details will only be available after oral presentations at the conference on Thursday 30th July.

For further details on study design and primary results of PURPOSE-1 and -2 please see previous reports from 2024. [3, 4]

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Although these early results continue to be impressive, having to report only top-line results from abstracts at a press conference doesn’t do justice to either the researchers or the study participants.

More than 40 other lencapavir PrEP studies are included in the conference programme including practical results from real-world programmes and critical issues of pricing and access.

The press conference also included:

• Two studies reporting the impact of cuts in PEPFAR funding cuts across 46 countries and with a focus on reductions in paediatric care.
• 48 week results once-weekly oral islatravir/lenacapavir in the phase 3 ISLEND-1 and -2 studies.
• Two new cases of HIV cure following allogeneic hematopoietic stem cell transplantation (HSCT) in the US and Germany.
• A cross-sectional study in 79 adolescents in the South African CHER cohort showing 1 in 5 had HIV-specific immune activity in CNS despite undetectable viral load in blood. 

References

1. Kiwanuka N et al. Zero HIV acquisitions with twice-yearly subcutaneous lenacapavir for PrEPduring 52 weeks of open-label extension in PURPOSE 1. Oral abstract OAC2802.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=1728 (Embargo lifted 27 July)
2. Losso M. High efficacy of twice-yearly subcutaneous lenacapavir for PrEP through 52 weeks of open-label extension in PURPOSE 2, Late-breaking oral abstract OAC2806LB.
   https://programme.aids2026.org/Abstract/Abstract/?abstractid=12509 (Embargo lifted 27 July)
3. AIDS 2024: Lenacapavir as PrEP is “beyond wonderful” but PURPOSE 1 study tells us so much more. HTB 19 July 2024.
   https://i-base.info/htb/48260
4. Kelley CF et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. NEJM N Engl J Med 2025392:1261-1276. DOI: 10.1056/NEJMoa2411858. (27 November 2024).
   https://www.nejm.org/doi/abs/10.1056/NEJMoa2411858