CONFERENCE UPDATE: CROI 2025

Twice yearly lenacapavir demonstrates high efficacy for HIV prevention and safety in adolescents and adults: Insights from PURPOSE 1

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

Efficacy endpoints:

  • Prespecified analyses included primary comparisons of LEN and F/TAF against background HIV incidence1

  • The observed background HIV incidence was 2.41 per 100 person-years (PY). HIV incidence rates in adults were 2.02 per

    100 PY for those who received F/TAF and 1.69 per 100 PY for those who received F/TDF1

  • LEN showed 100% efficacy, with no reported HIV infections over 1,939 PY1

  • Zero HIV infections were observed in adolescents across all study arms (LEN, F/TAF, and F/TDF

Safety:
  • Adverse events (AEs) were generally similar between adolescents and adults receiving LEN (94.6% vs. 88.3%)1

  • The most common AEs (excluding injection-site reactions) were headache (16.1% adolescents, 13.2% adults), and genitourinary chlamydia (12.5% adolescents, 14.1% adults)1

  • Injection-site reactions were common. Injection-site nodules occurred in 75.0% of adolescents and 63.5% of adults, while injection-site pain was reported in 32.1% and 31.2%, respectively1

  • Serious AEs and study drug discontinuations were rare. Only 1 adolescent (1.8%) experienced a serious AE, compared to 2.8% of adults, and no adolescents discontinued LEN due to AEs (vs. 0.2% in adults)1

  • Laboratory abnormalities were mostly low grade and similar between age groups. Grade ≥1 abnormalities occurred in 89.1% of adolescents and 90.7% of adults, with grade ≥3 abnormalities reported in 10.9% and 5.3%, respectively1

Exploratory analysis:
  • The exploratory analysis assessed LEN plasma trough concentrations (Ctrough) at week 26 in adolescents (ages 16-17 years) and adults (ages 18-25 years)1

  • The median Ctrough was 31.1ng/mL in adolescents (n=41) and 29.8ng/mL in adults (n=156), indicating generally comparable LEN exposure between the two groups1

 

"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

Get access to our exclusive articles.
Related Articles

Outcomes of NADIA trial at 96 weeks

After failure with emtricitabine (FTC) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs), the recommended second-line treatment regimen for human immunodeficiency virus (HIV) from the World Health Organization (WHO) is dolutegravir (DTG) with 2 NRTIs, tenofovir disoproxil fumarate (TDF) or zidovudine (ZDV).The efficacy of this regimen has not been proven as the activity of NRTIs is thought to be limited due to drug resistance.2 Similarly, drug resistance is expected when switching TDF to ZDV.2