What medications are recommended for HIV pre‑exposure prophylaxis (PrEP) in patients seeking prevention?

Recommended Medications for HIV Pre-Exposure Prophylaxis (PrEP)

Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) taken once daily is the primary recommended medication for HIV prevention in all individuals at risk of HIV infection. 1

Primary PrEP Regimens by Population

For Most Populations at Risk

• Daily oral TDF/FTC (300 mg/200 mg) is the first-line recommendation for all individuals at risk of HIV infection, including heterosexually active adults, people who inject drugs, and those with HIV-positive partners 1
• This regimen has the highest level of evidence (AIa) and is approved for all populations 1

For Men Who Have Sex With Men (MSM)

• Start with a double dose (2 tablets) of TDF/FTC on the first day, followed by once daily dosing to achieve maximal protection within 24 hours 1
• Alternative: 2-1-1 (on-demand) dosing is recommended exclusively for MSM—take 2 tablets 2-24 hours before sex, 1 tablet 24 hours later, and 1 final tablet 24 hours after that 1
• For MSM with kidney dysfunction, osteopenia, or osteoporosis: Daily tenofovir alafenamide/emtricitabine (TAF/FTC) is preferred over TDF/FTC 1

Injectable Long-Acting Option

• Cabotegravir injections every 8 weeks is recommended for cisgender men and transgender women who have sex with men 1
• This option provides superior efficacy compared to TDF/FTC (HR = 0.22,95% CI: 0.08-0.59) but requires injection site tolerance 2
• Long-acting cabotegravir is associated with less decreased creatinine clearance compared to TDF/FTC 2

Pre-Initiation Requirements

Mandatory Testing Before Starting PrEP

• Combined HIV antibody and antigen testing (fourth generation test) immediately before starting 1
• HIV RNA testing if acute HIV infection is suspected (symptoms or unprotected sex with HIV-positive person in preceding month) 1
• Serum creatinine with calculated creatinine clearance (must be ≥60 mL/min using Cockcroft-Gault formula for TDF/FTC) 1
• Hepatitis B surface antigen testing 1
• Hepatitis C antibody testing 1
• STI screening: Gonorrhea and chlamydia testing by nucleic acid amplification test (NAAT) at all exposure sites 1
• Pregnancy testing for individuals of childbearing potential 1

Rapid PrEP Start Approach

• If HIV test results from within the past 7 days are negative, initiate PrEP immediately while awaiting further diagnostics 1
• Do not delay PrEP initiation for other laboratory results if HIV testing is negative 1

Monitoring While on PrEP

At 1 Month

• Combined HIV antibody and antigen test 1

Every 2-3 Months (Quarterly)

• HIV testing with combined antibody/antigen test 1
• Creatinine clearance at first quarterly visit, then annually (more frequently if kidney injury risk) 1
• STI screening (gonorrhea, chlamydia at all contact sites, syphilis) 1
• Pregnancy testing for those of childbearing potential 1
• Adherence assessment and risk-reduction counseling 1

Every 6 Months

• Bacterial STI testing even if asymptomatic 1
• Hepatitis C antibody testing for people who inject drugs and MSM who use recreational drugs during sex 1

Special Populations and Considerations

Pregnant and Breastfeeding Individuals

• Daily TDF/FTC is recommended during pregnancy for those at ongoing risk 1
• Counsel that safety data during pregnancy are incomplete but no harm has been reported to date 1
• Do not prescribe PrEP to individuals who are breastfeeding per older guidance 1, though newer evidence supports daily TDF/FTC during breastfeeding 1

Individuals with Hepatitis B Co-infection

• TDF/FTC serves dual purpose as both HIV prevention and hepatitis B treatment 1
• If PrEP is discontinued in someone with active hepatitis B, ensure appropriate hepatitis B treatment is continued 1

Adherence Requirements for Efficacy

• For cisgender women: Consistently high adherence (4-6 doses/week) or daily dosing is required for protection 3, 4
• Women with consistently daily or high adherence (≥4 doses/week) had HIV incidence rates of 0-0.13 per 100 person-years 3
• For MSM: Protection is achieved with 4 or more doses per week 1
• Continue TDF/FTC for 2 days after last exposure in MSM, or 7 days after last exposure in others 1

Common Pitfalls to Avoid

• Never prescribe PrEP without confirming HIV-negative status first—this can lead to resistance if the person has undiagnosed HIV 1
• Do not use 2-1-1 dosing in populations other than MSM—insufficient evidence exists for efficacy in women or people who inject drugs 1
• Do not prescribe more than a 90-day supply without repeat HIV testing to confirm ongoing HIV-negative status 1
• Monitor kidney function appropriately—TDF/FTC requires creatinine clearance ≥60 mL/min; use TAF/FTC for those with clearance 30-60 mL/min 1
• Ensure comprehensive prevention services—PrEP must be delivered with risk-reduction counseling, condom access, and STI screening, not as standalone medication 1