N Engl J Med

Twice-yearly lenacapavir highly effective for HIV prevention in high-risk women

July 30, 2024

Among adolescent girls and young women in South Africa and Uganda, no study participants receiving biannual lenacapavir acquired HIV infection.

In the phase 3 PURPOSE 1 trial, adolescent girls and young women in South Africa and Uganda were assigned in a 2:2:1 ratio to receive SC lenacapavir q26wks, daily PO emtricitabine-tenofovir alafenamide (F/TAF), or daily PO emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate SC or PO placebo.

Among 5,338 participants who were initially HIV-negative, 55 incident HIV infections were recorded:

• 0 infections among 2,134 participants in the lenacapavir group (0 per 100 person-years)
• 39 infections among 2,136 participants in the F/TAF group (2.02 per 100 person-years)
• 16 infections among 1,068 participants in the F/TDF group (1.69 per 100 person-years)

Background HIV incidence in the screened population (n=8,094) was 2.41 per 100 person-years. HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio [IRR], 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (IRR, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF didn’t differ significantly from background HIV incidence (IRR, 0.84; 95% CI, 0.55 to 1.28; P = 0.21). The rate of HIV incidence was similar between F/TAF and F/TDF (IRR, 1.20; 95% CI, 0.67 to 2.14).

Low adherence to F/TAF and F/TDF was observed. No new safety signals were detected. Injection-site reactions were more common in the lenacapavir group (68.8%) vs. the placebo injection group (F/TAF and F/TDF combined; 34.9%). The rate of discontinuation due to injection-site reaction was 0.2% (4 participants) in the lenacapavir group.

Source:

Bekker LG, at al; PURPOSE 1 Study Team. (2024, August). N Engl J Med. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. https://pubmed.ncbi.nlm.nih.gov/39046157/