Lenacapavir Outperforms Daily Emtricitabine–Tenofovir for HIV Prevention
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on May 2nd, 2025
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Although the global number of new HIV infections is declining, infections among men who have sex with men and transgender women are rising. Pre-exposure prophylaxis (PrEP) is an effective method to prevent HIV transmission, but it requires consistent adherence to maintain its efficacy. To explore alternative prevention strategies, a study funded by Gilead Sciences evaluated the use of lenacapavir for HIV prevention.
This phase 3 clinical trial enrolled 3,265 HIV-negative gay or bisexual men and transgender women who reported having condomless sex with other men. About 23% of participants had a sexually transmitted infection at baseline. Participants were randomly assigned to receive either the standard daily oral PrEP regimen of emtricitabine and tenofovir disoproxil fumarate or lenacapavir. Emtricitabine and tenofovir, both nucleotide analogues, inhibit the reverse transcriptase enzyme essential for viral replication. They were administered daily at doses of 200 mg and 300 mg, respectively. In contrast, lenacapavir, which disrupts HIV capsid assembly by binding to the p24 subunit, was administered subcutaneously at a dose of 927 mg every 26 weeks. Its long half-life offers the advantage of biannual dosing, potentially improving adherence by reducing missed doses.
After 52 weeks, lenacapavir demonstrated a significantly lower incidence of HIV infection compared to the daily emtricitabine and tenofovir regimen. The frequency of adverse events was comparable between the two groups. The researchers highlighted that lenacapavir is already approved for treating multidrug-resistant HIV, although cases of resistance through capsid mutations have been reported. Additionally, they noted that HIV infections among participants in the daily oral PrEP group largely occurred among individuals with higher exposure risk and repeated mucosal injuries.
This phase 3 clinical trial enrolled 3,265 HIV-negative gay or bisexual men and transgender women who reported having condomless sex with other men. About 23% of participants had a sexually transmitted infection at baseline. Participants were randomly assigned to receive either the standard daily oral PrEP regimen of emtricitabine and tenofovir disoproxil fumarate or lenacapavir. Emtricitabine and tenofovir, both nucleotide analogues, inhibit the reverse transcriptase enzyme essential for viral replication. They were administered daily at doses of 200 mg and 300 mg, respectively. In contrast, lenacapavir, which disrupts HIV capsid assembly by binding to the p24 subunit, was administered subcutaneously at a dose of 927 mg every 26 weeks. Its long half-life offers the advantage of biannual dosing, potentially improving adherence by reducing missed doses.
After 52 weeks, lenacapavir demonstrated a significantly lower incidence of HIV infection compared to the daily emtricitabine and tenofovir regimen. The frequency of adverse events was comparable between the two groups. The researchers highlighted that lenacapavir is already approved for treating multidrug-resistant HIV, although cases of resistance through capsid mutations have been reported. Additionally, they noted that HIV infections among participants in the daily oral PrEP group largely occurred among individuals with higher exposure risk and repeated mucosal injuries.