Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis - United States, 2025.

In 2023, approximately 39,000 persons received a diagnosis of HIV in the United States. Although HIV preexposure prophylaxis (PrEP) is highly effective in preventing HIV infection, acceptance of, adherence to, and persistence taking the available oral and injectable PrEP regimens have been suboptimal. CDC PrEP guidelines published in 2021 include two oral tenofovir-based regimens and cabotegravir, the only injectable PrEP regimen approved by the Food and Drug Administration (FDA) at that time. In June 2025, FDA approved injectable lenacapavir (LEN), administered every 6 months, as HIV PrEP based on results from two randomized controlled trials (PURPOSE 1 and PURPOSE 2). The CDC PrEP Guidelines Work Group assessed evidence for the efficacy and safety of LEN PrEP using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The two trials reported LEN efficacy at reducing HIV infection as 100% among females and 96% among a primarily male trial population, compared with the estimated background HIV incidence (or no use of PrEP) over a follow-up of 52 weeks. No significant safety concerns were identified in the trials. The most common adverse events were mild (grade 1) to moderate (grade 2) injection site reactions. Based on a high certainty of evidence for the efficacy and safety of LEN as assessed by the GRADE analysis, subcutaneous injection of LEN every 6 months is strongly recommended as a PrEP option in persons weighing ≥77 lbs (≥35 kg) who would benefit from PrEP. LEN has the potential to improve PrEP adherence and thus enhance HIV prevention in the United States.