Long-Acting Lenacapavir Shows Superior HIV Prevention Over Daily Tenofovir Due to Improved Adherence
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on November 15th, 2024
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The combination of emtricitabine and tenofovir disoproxil fumarate is widely used as a preexposure prophylaxis (PrEP) to prevent HIV infection, with tenofovir alafenamide offering a higher cellular uptake as an alternative. However, the daily dosing requirement can lead to adherence challenges. Lenacapavir, a novel agent that targets the HIV capsid, has shown promise for PrEP with only twice-yearly subcutaneous injections. Consequently, Gilead sponsored a study to evaluate the effectiveness of lenacapavir compared to tenofovir-based regimens as PrEP for HIV prevention.
The phase 3 clinical trial was conducted in Uganda and South Africa, enrolling 5,338 HIV-negative women with a median age of about 21 years. Participants were randomly assigned to receive either lenacapavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. Lenacapavir was administered subcutaneously at a dose of 927 mg every 26 weeks, while tenofovir alafenamide and tenofovir disoproxil fumarate were given orally in daily doses of 25 mg and 300 mg, respectively, each paired with 200 mg of emtricitabine. After 52 weeks, none of the participants treated with lenacapavir contracted HIV, while both tenofovir regimens showed low effectiveness due to poor adherence—nearly 90% of participants took less than two doses per week of the required seven-dose weekly regimen. The researchers noted no significant difference in adverse effects among the groups, suggesting that poor adherence was likely due to stigma around medication use and the challenge of establishing a daily pill-taking routine rather than side effects.
The phase 3 clinical trial was conducted in Uganda and South Africa, enrolling 5,338 HIV-negative women with a median age of about 21 years. Participants were randomly assigned to receive either lenacapavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. Lenacapavir was administered subcutaneously at a dose of 927 mg every 26 weeks, while tenofovir alafenamide and tenofovir disoproxil fumarate were given orally in daily doses of 25 mg and 300 mg, respectively, each paired with 200 mg of emtricitabine. After 52 weeks, none of the participants treated with lenacapavir contracted HIV, while both tenofovir regimens showed low effectiveness due to poor adherence—nearly 90% of participants took less than two doses per week of the required seven-dose weekly regimen. The researchers noted no significant difference in adverse effects among the groups, suggesting that poor adherence was likely due to stigma around medication use and the challenge of establishing a daily pill-taking routine rather than side effects.