Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women | New England Journal of Medicine (nejm.org)
Population:
Study Participants: Adolescent girls and young women in South Africa and Uganda.
Sample Size: 5338 participants who were initially HIV-negative.
Intervention:
Primary Intervention: Subcutaneous lenacapavir administered every 26 weeks.
Secondary Intervention: Daily oral emtricitabine–tenofovir alafenamide (F/TAF).
Comparison:
Active Control: Daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF).
Background Comparison: Estimated background HIV incidence in the screened population.
Outcome:
Primary Outcome: Incidence of HIV infection.
Lenacapavir Group: 0 HIV infections (0 per 100 person-years; 95% CI, 0.00 to 0.19).
F/TAF Group: 39 HIV infections (2.02 per 100 person-years; 95% CI, 1.44 to 2.76).
F/TDF Group: 16 HIV infections (1.69 per 100 person-years; 95% CI, 0.96 to 2.74).
Background HIV Incidence: 2.41 per 100 person-years (95% CI, 1.82 to 3.19).
Statistical Significance:
Lenacapavir was significantly more effective than both background incidence (P<0.001) and F/TDF (P<0.001).
No significant difference between F/TAF and background incidence (P=0.21).
No significant difference between F/TAF and F/TDF (P=0.21).
Adverse Effects: Injection-site reactions were more common with lenacapavir (68.8%) compared to placebo (34.9%), with 4 participants (0.2%) discontinuing due to these reactions.
Clinical Insights
This study demonstrates that subcutaneous lenacapavir, administered every 26 weeks, significantly reduces HIV incidence in adolescent girls and young women in South Africa and Uganda compared to both the background incidence and the current standard daily oral PrEP regimens (F/TAF and F/TDF). Lenacapavir’s biannual dosing could address adherence issues associated with daily oral PrEP, offering a promising alternative for HIV prevention in populations with poor adherence. However, the higher rate of injection-site reactions with lenacapavir should be considered when evaluating patient suitability. This could inform HIV prevention strategies, particularly in resource-limited settings or populations with adherence challenges.