Lenacapavir Looks to Revolutionize HIV Prevention

PrEP (pre-exposure prophylaxis) has revolutionized biomedical HIV prevention but as a method to protect individuals from acquiring HIV its uptake needs a boost, especially among certain populations such as cisgender and transgender women and men of color who have sex with men, among others. That boost could come in many forms—a lower cost to make the regimen more accessible, engagement with groups vulnerable to HIV to make at-risk individuals aware of their options, and less frequent dosing to make adherence easier.

Twice-yearly injectable lenacapavir, an HIV antiretroviral now being investigated as PrEP in a series of trials, may turn out to be a boon to uptake, especially if its costs are kept down.

Conducted by Gilead Sciences, two of these trials, PURPOSE 1 and PURPOSE 2, have been completed, and in both lenacapavir shows superior efficacy to once-daily oral Truvada.

In PURPOSE 1, which enrolled 5,338 cisgender adolescent girls and young women in Uganda and South Africa, lenacapavir demonstrated 100% efficacy, with participants injected with the drug registering zero infections.

Responding to social determinants of health as drivers of HIV acquisition—socioeconomic inequity, racism, stigma, homophobia, transphobia, and other factors—the clinical trial designers included underrepresented groups that are disproportionately affected by the pandemic.

The PURPOSE 2 study, conducted at sites in the United States, South Africa, Peru, Brazil, Argentina, Mexico, and Thailand, enrolled 3,200 cisgender men, transgender women, transgender men, and gender non-binary individuals who have sex with partners assigned male at birth.

While the results of an interim analysis of the PURPOSE 2 study do not match the 100% efficacy found in PURPOSE 1, they are still remarkable.

In the Phase 3 trial, 99.9% of participants in the lenacapavir group did not acquire HIV, with two individuals seroconverting among 2,180 enrollees. Findings show that twice-yearly injectable lenacapavir for HIV prevention reduced HIV acquisitions by 96% compared to expected HIV acquisitions overall. In this trial, lenacapavir was shown to have an 89% lower HIV acquisition rate compared to once-daily oral Truvada.

In response to the PURPOSE 2 findings, Gilead Sciences stopped the blinded phase of the trial and offered lenacapavir to all participants.

A series of global regulatory filings will be started by Gilead by the end of 2024. PURPOSE 3, studying cisgender women in the U.S., and PURPOSE 4, studying people who inject drugs, are still ongoing.

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