What is the recommended prophylaxis regimen for individuals at high risk of HIV exposure?

HIV Prophylaxis: Recommended Regimens

For individuals at high risk of HIV exposure, prescribe tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg once daily as the first-line pre-exposure prophylaxis (PrEP) regimen, which provides >90% efficacy when adherence is maintained. 1, 2, 3

Pre-Exposure Prophylaxis (PrEP)

Standard First-Line Regimen

TDF/FTC 300mg/200mg once daily is the gold standard oral PrEP across all populations and exposure routes. 3 This regimen has the strongest evidence rating (AIa) from multiple randomized controlled trials demonstrating substantial risk reduction. 3, 4, 5

Population-Specific Dosing Strategies

Men Who Have Sex with Men (MSM)

• Initiate with a loading dose of 2 tablets on day 1, then continue once daily thereafter to achieve maximal protection within 24 hours 1, 3
• Alternative on-demand "2-1-1" dosing is acceptable for MSM only: 2 tablets taken 2-24 hours before sex, 1 tablet 24 hours later, and 1 tablet 48 hours after the first dose 1, 3
• When stopping PrEP, continue for 2 days after the last at-risk exposure 1

Cisgender Women and Transgender Women

• Daily dosing is mandatory—on-demand dosing is NOT recommended for vaginal exposure 2, 3
• Take once daily without loading dose 1
• Maximum protection requires approximately 7 days of daily dosing 1, 2
• When stopping PrEP, continue for 7 days after the last at-risk exposure 1
• Daily dosing is critical because tenofovir concentrates at 10-fold lower levels in vaginal tissue compared to rectal tissue, with faster clearance 1

Who Should Receive PrEP

PrEP should be discussed with all sexually active adults and adolescents and individuals who inject drugs. 1 High-risk populations include:

• MSM with: condomless anal intercourse in the past 6 months, multiple male sex partners, HIV-positive partner(s), recent STI diagnosis, methamphetamine or stimulant use, or risk score ≥10 on validated assessment tools 2
• Transgender women: engaging in condomless anal intercourse or with multiple partners 2
• Heterosexual individuals with: HIV-positive sexual partner, inconsistent condom use with partners of unknown HIV status, recent bacterial STI diagnosis, or HIV incidence >2% per year in their sexual network 2
• Injection drug users: who share injection equipment 4

Pre-Initiation Testing Requirements

Before prescribing PrEP, obtain the following tests: 1, 2, 3

• Combined HIV antibody and antigen testing
• Serum creatinine with calculated creatinine clearance
• Hepatitis B surface antigen (HBsAg)
• Hepatitis C antibody
• Nucleic acid amplification testing for gonorrhea and chlamydia (urogenital, rectal, and pharyngeal sites as appropriate)
• Syphilis testing
• Pregnancy test for individuals of childbearing potential

Monitoring Schedule During PrEP Use

Every 3 months, perform: 1, 2, 3

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

Renal function monitoring: 2, 3

• At 3 months after initiation, then every 6 months
• More frequent monitoring if baseline creatinine clearance <90 mL/min, diabetes, hypertension, or age >50 years

Additional monitoring: 1

• HIV testing at 1 month after initiation

Alternative Regimen: TAF/FTC

Tenofovir alafenamide/emtricitabine (TAF/FTC) should be considered ONLY for MSM with creatinine clearance 30-60 mL/min or osteopenia/osteoporosis. 1, 2

Critical caveat: TAF/FTC lacks efficacy data for receptive vaginal sex and should NOT be used as first-line for cisgender women. 2

Special Populations

Pregnancy and Breastfeeding

TDF/FTC is safe during pregnancy and breastfeeding with no documented adverse fetal effects and should be continued. 1, 2, 3 This is the preferred regimen during pregnancy and breastfeeding. 2

Hepatitis B Co-infection

For HBsAg-positive individuals, consider indefinite continuation or transition to hepatitis B treatment if stopping PrEP, as discontinuation can cause hepatitis flares. 1, 2, 3 Monitor closely with ALT/AST testing after discontinuation. 2, 3

Adolescents

Adolescents are classified in the same category as adults for PrEP prescribing, with TDF/FTC as the preferred regimen. 2 Enhanced adherence counseling is essential for all adolescents initiating PrEP. 1, 2

Efficacy and Adherence

PrEP efficacy exceeds 90% when adherence is maintained with detectable drug levels. 1, 2, 3, 4 However, efficacy is highly adherence-dependent, dropping to 44% with suboptimal adherence versus 92% with detectable drug levels. 1, 2, 5

Common Pitfalls to Avoid

• Do NOT prescribe PrEP without confirming HIV-negative status, as resistance can develop if prescribed during acute HIV infection 3
• Do NOT use on-demand (2-1-1) dosing for cisgender women or transgender women—daily dosing is mandatory for vaginal exposure 2, 3
• Do NOT use TAF/FTC as first-line for cisgender women due to insufficient efficacy data for vaginal exposure 2
• Do NOT forget the 7-day lead-in period for women, as protection is not immediate 2, 3
• Counsel that PrEP does not prevent other STIs—condoms remain essential for comprehensive STI prevention 1, 3
• Resistance to TDF/FTC when used for PrEP is rare (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection 4

Post-Exposure Prophylaxis (PEP)

For post-exposure prophylaxis, initiate treatment as soon as possible after exposure without waiting for confirmation of HIV serostatus of the source patient. 6

Recommended PEP Regimens

TDF/emtricitabine plus twice-daily raltegravir or once-daily dolutegravir is the CDC-recommended regimen for post-exposure prophylaxis. 6 Reasonable alternatives include TDF/emtricitabine with cobicistat- or ritonavir-boosted darunavir or TDF/emtricitabine/cobicistat/elvitegravir. 6

Duration and Follow-up

Continue PEP regimens for 28 days, and reassess HIV serostatus at 4 to 6 weeks, 3 months, and 6 months after exposure. 6 Shorter follow-up (3 or 4 months) may be possible with a fourth-generation assay. 6

Transition from PEP to PrEP

For persons with anticipated repeat or ongoing HIV exposures, immediately transition from post-exposure prophylaxis to PrEP, with HIV testing at completion of the PEP regimen before transitioning. 2