What is the recommended pre-exposure prophylaxis (PrEP) medication regimen for individuals at high risk of Human Immunodeficiency Virus (HIV) exposure?

Recommended Pre-Exposure Prophylaxis (PrEP) Medication Regimens for HIV Prevention

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is the recommended first-line PrEP regimen for all individuals at high risk of HIV infection. 1

First-Line PrEP Options by Population

For All Populations at Risk for HIV Infection:

• Daily oral TDF/FTC (300mg/200mg) is recommended as the standard PrEP regimen with proven efficacy across all risk groups 1
• For initiation in men who have sex with men (MSM), a double dose (2 pills) of TDF/FTC is recommended on the first day, followed by daily dosing 1
• Daily dosing should be maintained for continued protection, with dosing to continue until 2 doses after last sexual activity for rectal exposures 1
• For vaginal, neovaginal, or "front-hole" exposures, dosing should continue until at least 7 days after last sexual activity 1

For MSM and Transgender Women Who Have Sex with Men:

• On-demand (2-1-1) oral dosing of TDF/FTC is an alternative option for cisgender men and others having planned receptive anal sex 1
  • Involves taking a double dose 2-24 hours before sexual activity, followed by single doses 24 and 48 hours after the first dose 1
  • Not recommended for vaginal exposures or people who inject drugs 1
• Injectable cabotegravir every 8 weeks is recommended (pending regulatory approval and availability) 1
• For those with or at risk for kidney dysfunction, osteopenia, or osteoporosis, daily tenofovir alafenamide/emtricitabine (TAF/FTC) is recommended 1, 2

For Cisgender Women and Heterosexual Men:

• Daily oral TDF/FTC is the only recommended option with proven efficacy 3
• Daily dosing is critical for females as tenofovir concentrates at 10-fold lower levels in vaginal tissue than in rectal tissue 3
• TAF/FTC is NOT currently recommended for cisgender women or prevention of HIV infection from receptive vaginal sex 2

Pre-Initiation Testing Requirements

Before starting PrEP, the following tests should be performed 1, 3:

• Combined HIV antibody and antigen testing (HIV RNA level if clinical suspicion of acute HIV)
• Serum creatinine level and estimated creatinine clearance
• Hepatitis B surface antigen
• Hepatitis C IgG antibody
• Genital and nongenital Neisseria gonorrhea and Chlamydia trachomatis testing by nucleic acid amplification test (NAAT)
• Pregnancy testing for individuals of childbearing potential

Monitoring Recommendations

• HIV testing at 1 month and quarterly thereafter 2
• Creatinine clearance at first quarterly visit and annually thereafter 2
• STI testing quarterly 2, 3
• PrEP prescriptions should not exceed 90 days without interval testing for HIV infection 3

Important Considerations and Caveats

• PrEP efficacy is highly dependent on adherence - studies show that good medication compliance can reduce HIV infection risk by 53-62% 4
• Unlike condoms, PrEP does not prevent other sexually transmitted infections 3
• Significant racial and ethnic disparities exist in PrEP access and utilization in the United States 5
• For people who inject drugs, clean injection equipment and access to substance use treatment should be available alongside PrEP 3
• Generic lamivudine/tenofovir disoproxil fumarate (3TC/TDF) may be considered as a cost-effective alternative to FTC/TDF in resource-limited settings 6

Special Populations

• PrEP is safe for use during pregnancy and breastfeeding, with TDF/FTC being the recommended regimen 1
• Long-acting cabotegravir has a growing safety profile in pregnancy and breastfeeding 1
• For MSM with renal impairment (creatinine clearance between 30-60 mL/min) or bone health concerns, TAF/FTC is preferred over TDF/FTC 2

PrEP should be discussed and offered to all sexually active persons, all persons requesting PrEP, and anyone who injects nonprescription drugs or uses substances, without limiting access based on specific criteria for sexual or drug use behavior 1.