What is the recommended Antiretroviral Therapy (ART) prophylaxis regimen for individuals at high risk of HIV acquisition?

Recommended ART Prophylaxis for HIV Prevention

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg once daily is the first-line PrEP regimen for all individuals at high risk of HIV acquisition, with proven efficacy exceeding 90% when adherence is maintained. 1

Primary PrEP Regimen

TDF/FTC remains the gold standard oral PrEP option across all populations and exposure routes. 1, 2 This recommendation is supported by the most recent 2024 International Antiviral Society-USA guidelines and has the strongest evidence rating (AIa). 1

• The efficacy is highly adherence-dependent: 92% risk reduction with detectable drug levels versus 44% with suboptimal adherence 3, 4
• Resistance to TDF/FTC when used for PrEP is rare (<0.1%) and typically occurs only when inadvertently prescribed during undiagnosed acute HIV infection 3

Population-Specific Dosing Strategies

Men Who Have Sex With Men (MSM)

• Standard regimen: TDF/FTC 300mg/200mg once daily 1
• Loading dose: Double dose (2 pills) on the first day is recommended 1
• Alternative on-demand dosing (2-1-1 method): Recommended ONLY for MSM—2 pills 2-24 hours before sex, 1 pill 24 hours after first dose, 1 pill 48 hours after first dose 1

Cisgender Women and Transgender Women

• Daily dosing is mandatory—on-demand dosing is NOT recommended for vaginal exposure 2, 5, 6
• Tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, and clearance is faster 5, 6
• Minimum 7-day lead-in period is required before adequate protection is achieved for vaginal exposures 2, 5

Special Populations Requiring Alternative Regimens

For MSM with renal dysfunction (CrCl <60 mL/min), osteopenia, osteoporosis, or age >50 years: Daily tenofovir alafenamide/emtricitabine (TAF/FTC) is recommended 1, 2

Injectable cabotegravir: Long-acting injectable cabotegravir every 8 weeks is recommended for cisgender men and transgender women who have sex with men (pending regulatory approval and availability) 1

Pre-Initiation Requirements (Mandatory Testing)

Before prescribing PrEP, the following tests are required 1, 2:

• Combined HIV antibody and antigen testing (HIV RNA if clinical suspicion of acute HIV exists)
• Serum creatinine with calculated creatinine clearance
• Hepatitis B surface antigen (HBsAg)
• Hepatitis C IgG antibody (if positive, confirm HCV RNA)
• Comprehensive STI screening: Genital and nongenital gonorrhea and chlamydia by NAAT
• Pregnancy test for individuals of childbearing potential
• Hepatitis A IgG antibody for MSM and people who inject drugs (if not known to be immune)

Critical caveat: PrEP should NOT be initiated until HIV RNA test results confirm uninfected status if there is clinical suspicion of acute HIV infection 1

Monitoring Schedule During PrEP Use

Quarterly Monitoring (Every 3 Months) 1, 2

• HIV antibody/antigen testing
• STI screening (gonorrhea, chlamydia, syphilis)
• Pregnancy testing for individuals of childbearing potential
• Adherence assessment

Renal Function Monitoring 1, 2

• At 3 months after initiation, then every 6 months for routine monitoring
• More frequent monitoring (every 3 months) for individuals with baseline CrCl <90 mL/min, diabetes, hypertension, or age >50 years

PrEP prescriptions should not exceed 90 days without interval HIV testing. 6

Pregnancy and Breastfeeding

TDF/FTC is safe during pregnancy and breastfeeding and should be continued. 1, 2, 5 No adverse fetal effects have been documented in infants exposed during pregnancy. 2, 5

Hepatitis B Co-infection

For HBsAg-positive individuals: If PrEP is discontinued, consider indefinite continuation or transition to hepatitis B treatment, with close monitoring for hepatitis flares using ALT/AST testing. 2 Abrupt discontinuation can cause severe hepatitis B flares.

Common Pitfalls to Avoid

1. Do not use on-demand (2-1-1) dosing for cisgender women or transgender women—daily dosing is mandatory for vaginal exposure 1, 5
2. Do not prescribe PrEP without confirming HIV-negative status—resistance can develop if prescribed during acute HIV infection 1, 3
3. Do not use TAF/FTC as first-line for cisgender women—insufficient efficacy data exists for vaginal exposure 1
4. Do not forget the 7-day lead-in period for women—protection is not immediate 2, 5
5. Counsel that PrEP does not prevent other STIs—condoms remain essential for comprehensive STI prevention 5, 6

Safety Profile

Only 2% of individuals discontinue PrEP due to adverse effects. 5, 3 Common side effects (nausea, headache) are typically self-limited and resolve within the first month. 5 Bone and renal adverse event incidence rates are 0.69 and 11.8 per 100 person-years, respectively. 4