CDC 2025 Clinical Recommendation for Injectable Lenacapavir as HIV Pre-Exposure Prophylaxis (with 2024 CDC Doxy-PEP Guidelines)
CDC strongly recommends twice-yearly injectable lenacapavir as an HIV PrEP option alongside existing oral and injectable regimens. Read together with CDC's 2024 doxycycline post-exposure prophylaxis recommendation for bacterial STI prevention in MSM and transgender women.
What changed in this edition
- Lenacapavir 927 mg subcutaneous every 26 weeks recommended for HIV PrEP in persons ≥35 kg who would benefit (MMWR 74(35), Sept 18, 2025).
- Lenacapavir joins daily oral TDF/FTC, daily oral TAF/FTC, and every-2-month injectable cabotegravir as PrEP options.
- CDC 2024 doxycycline PEP (200 mg within 72 hours of condomless sex) recommended for MSM and transgender women with prior bacterial STI in the past 12 months.
- HIV testing with 4th-gen Ag/Ab plus HIV-1 RNA required before initiation and at every injection for long-acting agents.
- Counseling required on the pharmacologic tail (residual drug) period after injectable PrEP discontinuation; oral bridging recommended.
- TDF/FTC retains creatinine thresholds (eGFR ≥60); TAF/FTC usable at eGFR ≥30.
- PrEP offer recommended to any sexually active adult or adolescent at ongoing risk, regardless of self-identified risk.
Clinical takeaways
Who should be offered PrEP
Any sexually active adult or adolescent at ongoing risk; do not require patients to self-identify risk. People who inject drugs; serodifferent partners; transgender and nonbinary adults. Offer during routine care.
Regimen choice
Lenacapavir every 6 months or CAB-LA every 2 months when adherence to daily oral dosing is a barrier. Oral TDF/FTC remains first-line for most, including cisgender women; TAF/FTC for cisgender men and transgender women who have sex with men.
Monitoring cadence
Baseline: HIV Ag/Ab, HIV-1 RNA, hepatitis B and C, syphilis, GC/CT (three-site), pregnancy test if applicable, creatinine and phosphate for TDF. Follow-up every 3 months (oral/injectable) with full STI panel.
Doxy-PEP integration
Co-prescribe with PrEP for eligible MSM and transgender women with a prior bacterial STI in the last 12 months. 200 mg PO once within 72 hours of sex, max every 24 hours.
Discontinuation
Counsel on the pharmacologic tail for injectables; provide oral bridging if long-acting is stopped. Confirm HIV-negative status at any switch or discontinuation.
Supporting trials
- PURPOSE-1PubMed 39046157
Twice-yearly lenacapavir had zero HIV infections in cisgender women (vs 2.02/100 PY on F/TAF).
- PURPOSE-2PubMed 39602624
Lenacapavir reduced HIV infections by 96% vs background in MSM and gender-diverse populations.
- HPTN 083PubMed 34379922
Injectable cabotegravir superior to daily TDF/FTC in cisgender men and transgender women.
- HPTN 084PubMed 35378077
CAB-LA superior to TDF/FTC for HIV prevention in cisgender women in sub-Saharan Africa.
- DoxyPEP (Luetkemeyer)PubMed 37018493
Doxycycline post-exposure reduced combined gonorrhea, chlamydia, and syphilis by two-thirds in MSM and transgender women on PrEP or with HIV.