STUDY DESIGN

Despite the high incidence of human immunodeficiency virus (HIV) infection among adolescents, this population has historically been excluded from phase 3 HIV trials.¹ As a result, clinical data on new therapeutic options in adolescents often become available years after adult approvals, delaying their access to pre-exposure prophylaxis (PrEP).¹ Daily adherence to PrEP is also lower among adolescents than adults, highlighting the need for alternative strategies.¹ Lenacapavir (LEN) is a first-in-class, multistage HIV-1 capsid inhibitor with high potency and a long half-life, supporting twice-yearly subcutaneous (SC) injections.¹

The PURPOSE program is the first to intentionally include adolescents aged 16 and 17 years in an HIV prevention trial.¹ PURPOSE 1 was a randomized, blinded trial designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of LEN in adolescents compared to adults while implementing strategies to support adolescent participation.¹

In PURPOSE 1, cisgender women at risk of HIV infection were assigned to receive LEN subcutaneously every 26 weeks (n=2,134; adolescents: n=56), daily oral emtricitabine + tenofovir alafenamide (F/TAF) (n=2,136; adolescents: n=45), or daily oral emtricitabine + tenofovir disoproxil fumarate (F/TDF) as the active control (n=1,068; adolescents: n=23).¹ Before enrolling adolescents, an independent data monitoring committee reviewed safety data from the first 300 adult participants.¹ The study also included a cross-sectional incidence cohort to estimate background HIV incidence.¹ To ethically include adolescents, the study team engaged adolescent medicine experts and community advocates.¹ Site-specific strategies ensured appropriate consent processes, including community advisory board-facilitated consent waivers and self-consent for emancipated minors.¹ Trial sites also adapted procedures such as early morning and weekend visits to accommodate adolescent schedules.¹ Prespecified analyses included primary comparisons of LEN and F/TAF against background HIV incidence, secondary assessment of LEN’s safety in adolescents, and exploratory evaluation of LEN plasma concentrations.¹

FINDINGS

"LEN demonstrated 100% efficacy for HIV prevention in adolescent and adult cisgender women"

Dr. Katherine Gill
Desmond Tutu HIV Centre,
University of Cape Town,
South Africa