Title : Lenacapavir for HIV treatment and pre-exposure prophylaxis- evaluating efficacy and safety: A systematic review and meta-analysis
Abstract:
Background: Human Immunodeficiency Virus (HIV) remains a global health burden despite advances in antiretroviral therapy (ART). Challenges with daily adherence and multidrug resistance (MDR) necessitate novel approaches. Lenacapavir, a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months, offers a promising alternative for both treatment and prevention. This systematic review and meta-analysis evaluated the efficacy and safety of lenacapavir for HIV management and pre-exposure prophylaxis (PrEP).
Methods: A comprehensive search was conducted in PubMed, Web of Science, and Scopus up to 2025, including randomized controlled trials and cohort studies assessing lenacapavir in HIV-infected individuals and those at risk. Primary outcomes were HIV incidence, virologic suppression (HIV-1 RNA <50 copies/mL), CD4+ count changes, and adverse events. Data synthesis included qualitative analysis and meta-analyses using random-effects models.
Results: Six studies were included, encompassing treatment-naive individuals, MDR-HIV patients, and PrEP candidates. Meta-analysis of two large PrEP trials (n > 4,000) revealed a significant reduction in HIV incidence with lenacapavir (pooled OR 0.058; 95% CI: 0.009–0.360; p = 0.002). In MDR-HIV patients, 83% achieved virologic suppression at week 52 with lenacapavir plus optimized background therapy. Lenacapavir also showed comparable efficacy to standard ART in treatment-naive patients. While lenacapavir increased the odds of injection site reactions (pooled OR 3.055; p = 0.001) and nausea (pooled OR 0.542; p < 0.001), most adverse events were mild to moderate, with no significant difference in overall adverse event rates.
Conclusion: Lenacapavir offers highly effective, long-acting HIV prevention and treatment, particularly benefiting adherence-challenged and MDR-HIV populations. Despite some local and gastrointestinal side effects, its safety profile is favorable, representing a significant advance in HIV care.
