touchINFECTIOUS DISEASES coverage of IAS 2025:
PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752) were parallel phase III trials investigating the efficacy, safety, and pharmacokinetics (PK) of lenacapavir for HIV pre-exposure prophylaxis (PrEP) in adolescents and young people. In this interview we spoke with Dr Katherine Gill (The Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa) around the advantages of a long-acting therapy, the efficacy, safety and PK profile of lenacapavir, and the practical considerations for integrating lenacapavir into HIV prevention programmes in younger populations.
The abstract “Efficacy, safety, and pharmacokinetics of twice-yearly subcutaneous lenacapavir for PrEP among adolescents and young people in the phase 3 trials PURPOSE 1 and PURPOSE 2” was presented at IAS 2025, Kigali, Rwanda, 13–17 July 2025.
Long-acting lenacapavir offers a compelling alternative to daily oral PrEP for adolescents and young people. Administered just twice a year, it eliminates daily pill-taking challenges such as forgetfulness, stigma, and limited privacy. Its discreet injectable form reduces the risk of accidental disclosure and supports autonomy in HIV prevention. Lenacapavir can also interface seamlessly with long-acting contraceptive methods, allowing for synchronized clinic visits and streamlined care. This is particularly advantageous for young people seeking comprehensive sexual and reproductive health services. With consistent protection and youth-friendly delivery, lenacapavir represents a practical, empowering option for HIV prevention in this population.
In the PURPOSE 1 and 2 trials, long-acting subcutaneous lenacapavir demonstrated significantly greater efficacy in preventing HIV compared to daily oral PrEP among adolescents and young people aged 16–25. In PURPOSE 1, conducted among adolescent girls and young women in sub-Saharan Africa, lenacapavir achieved 100% efficacy, with zero incident HIV infections. In PURPOSE 2, among MSM, transgender, and gender-diverse individuals globally, lenacapavir reduced HIV incidence by 96% relative to the daily oral TDF/FTC group. These results underscore lenacapavir’s potential as a highly effective, youth-friendly PrEP option with minimal adherence burden and strong relevance for key populations.
Injection site reactions (ISRs) with lenacapavir were generally mild to moderate and similar between adolescents and adults across the PURPOSE 1 and 2 studies. The most common ISRs included pain, swelling, or redness at the injection site, typically resolving within a few days. Importantly, ISRs rarely led to discontinuation. Overall safety profiles were consistent between youth and adult participants, with no new safety signals identified in the adolescent group. These findings support the tolerability of lenacapavir in younger populations, reinforcing its suitability as a long-acting HIV prevention method that does not pose greater safety concerns for adolescents.
Pharmacokinetic analyses in youth from the PURPOSE 1 and 2 studies showed that lenacapavir plasma concentrations were comparable to those observed in adults, supporting consistent drug absorption, distribution, metabolism, and elimination across age groups. As a result, the standard adult dosing regimen provides effective and sustained drug levels in adolescents and young adults, supporting use without dose adjustment. The key caveat is that this applies to individuals weighing at least 35Kg. This simplifies clinical use, ensures reliable efficacy, and enhances the feasibility of implementing long-acting PrEP in younger populations without additional dosing complexity.
Practical considerations for integrating twice-yearly injectable PrEP into adolescent HIV prevention programmes include training healthcare providers on subcutaneous injection techniques and managing ISRs, with education for both staff and adolescents on what to expect and how to troubleshoot common side effects. Scheduling six-monthly visits requires robust appointment systems to support adherence. Providers must consider potential drug interactions, particularly those involving CYP enzymes, when prescribing lenacapavir alongside other medications. Confidentiality and discretion remain priorities to encourage adolescent uptake. Integration with sexual and reproductive health services, including contraception, and ongoing community engagement are vital for successful implementation.
The WHO’s endorsement of twice-yearly injectable lenacapavir represents a significant advance in HIV prevention, simplifying adherence by reducing dosing frequency and enabling community-based delivery through pharmacies and telehealth. This expands access for diverse populations, including adolescents and hard-to-reach groups. Complementing this, MK-8527 is an investigational once-monthly oral pill offering a convenient long-acting alternative to daily PrEP. Well tolerated in adults, MK-8527 is advancing to phase III trials in Africa, potentially broadening prevention options continent-wide. Funding cuts were also a major topic, highlighting ongoing challenges in sustaining HIV prevention and care programs.
Further content in HIV.
This content has been developed independently by Touch Medical Media for touchINFECTIOUS DISEASES. It is not affiliated with the International AIDS Society (IAS). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Abstract: Gill K, Abdool Karim Q, Anugulruengkitt S, et al. Efficacy, safety, and pharmacokinetics of twice-yearly subcutaneous lenacapavir for PrEP among adolescents and young people in the phase 3 trials PURPOSE 1 and PURPOSE 2. Presented at: IAS 2025, Kigali, Rwanda, 17 July: OAC0503.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchINFECTIOUS DISEASES in collaboration with Katherine Gill. touchINFECTIOUS DISEASES utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No fees or funding were associated with its publication.
Cite: Katherine Gill. PURPOSE 1 & 2: lenacapavir safe and effective for HIV PrEP in young populations. touchINFECTIOUS DISEASES. 30 July 2025.
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