New HIV Prevention Option Shows High Efficacy and Safety in US Clinical Trials

Strategic Insights -

Researchers from the Centers for Disease Control and Prevention (CDC) have announced a new HIV preexposure prophylaxis (PrEP) option that has shown high efficacy and safety in US clinical trials. According to the CDC, the injectable medication, lenacapavir (LEN), administered every 6 months, has been approved by the Food and Drug Administration (FDA) for use as an HIV PrEP. The CDC PrEP guidelines published in 2021 included two oral tenofovir-based regimens and cabotegravir, the only injectable PrEP regimen approved by the FDA at that time. However, the new injectable LEN has shown even higher efficacy in preventing HIV infection, with 96% effectiveness in a primarily male trial population and 100% effectiveness in females.

The CDC PrEP Guidelines Work Group assessed the 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 96% among a primarily male trial population and 100% among females, 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.

The CDC strongly recommends LEN as a PrEP option in persons weighing = 77 lbs ( = 35 kg) who would benefit from PrEP. This recommendation is based on a high certainty of evidence for the efficacy and safety of LEN as assessed by the GRADE analysis.

Key Takeaways:

  • Lenacapavir (LEN) is a new injectable HIV preexposure prophylaxis (PrEP) option that has been approved by the FDA as an HIV PrEP.
  • LEN has shown high efficacy in preventing HIV infection, with 96% effectiveness in a primarily male trial population and 100% effectiveness in females.
  • The CDC PrEP Guidelines Work Group assessed the 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 96% among a primarily male trial population and 100% among females, 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.
  • The CDC strongly recommends LEN as a PrEP option in persons weighing = 77 lbs ( = 35 kg) who would benefit from PrEP.
  • This recommendation is based on a high certainty of evidence for the efficacy and safety of LEN as assessed by the GRADE analysis.
  • LEN has the potential to improve PrEP adherence and thus enhance HIV prevention in the United States.

Statistics:

  • 39,000 persons received a diagnosis of HIV in the United States in 2023 (1).
  • LEN has a 96% effectiveness in preventing HIV infection in a primarily male trial population (2).
  • LEN has a 100% effectiveness in preventing HIV infection in females (2).
  • The FDA approved injectable lenacapavir (LEN) as HIV PrEP in June 2025 (3).

Sources:

  • Centers for Disease Control and Prevention. Clinical Recommendation for the Use of Injectable Lenacapavir As Hiv Preexposure Prophylaxis - United States, 2025. Mmwr-morbidity and Mortality Weekly Report, 2025;74(35).
  • NewsRx. Reports on HIV/AIDS Findings from Centers for Disease Control and Prevention Provide New Insights (Clinical Recommendation for the Use of Injectable Lenacapavir As Hiv Preexposure Prophylaxis - United States, 2025). Medical Letter on the CDC & FDA. October 26, 2025; p 653.