Twice-a-Year HIV Prevention Shot Leads to Zero Infections Among 2,134 Women in Phase 3

HIV pre-exposure prophylaxis (PrEP) has a weakness: it requires taking a pill every day, which is hard to keep up consistently. Professor Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town in South Africa and colleagues reported in NEJM the results of the phase 3 PURPOSE 1 trial, in which no infections occurred in the group that received subcutaneous injections of the HIV capsid inhibitor lenacapavir every 26 weeks.

Double-Blind Phase 3, 5,338 Compared

Adolescent girls and young women in South Africa and Uganda (5,338 in total) were assigned 2:2:1 to lenacapavir injections, daily F/TAF (emtricitabine and tenofovir alafenamide), or the existing standard drug F/TDF (active control group). All participants also received the matching placebo injection or pill to maintain blinding. The primary endpoint was the rate of new HIV infections, compared against the background infection rate estimated from the screened population (2.41 per 100 person-years) and against the F/TDF group. Among the 2,134 women in the lenacapavir group, there were 0 infections, compared with 2.02 per 100 person-years in the F/TAF group and 1.69 in the F/TDF group. Adherence was low in the two groups taking pills.

No new safety concerns were identified, but injection-site reactions were more frequent in the lenacapavir group (68.8%) than in the placebo injection group (34.9%), and 4 people (0.2%) stopped treatment because of them.

Significance and Limits

There is hope that if prevention becomes possible with two visits a year, the burden of daily pills and the problem of stigma could be eased. However, the participants were limited to cisgender women in two African countries, and the manufacturer (Gilead Sciences) funded the study. Long-term safety, the possibility of resistance, and actual supply prices and access still need to be confirmed.