What pre‑exposure prophylaxis should be offered to an HIV‑negative sexually active adult seeking protection against sexually transmitted infections?

Pre-Exposure Prophylaxis for Sexually Transmitted Diseases

For an HIV-negative sexually active adult seeking protection against sexually transmitted infections, offer daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg for HIV prevention, plus doxycycline 200mg post-exposure prophylaxis (DoxyPEP) within 72 hours after condomless sex for bacterial STI prevention. 1

HIV Pre-Exposure Prophylaxis (PrEP)

Universal Offer and First-Line Regimen

• PrEP should be discussed and offered to all sexually active persons, anyone requesting it, and individuals who inject drugs—without requiring formal risk-assessment tools or specific behavioral criteria. 1
• Daily oral TDF/FTC (300mg/200mg) remains the gold standard first-line regimen for all populations at risk of HIV acquisition, with proven efficacy exceeding 90% when adherence is maintained. 1, 2

Population-Specific Dosing Strategies

For cisgender men who have sex with men (MSM):

• Initiate with a loading dose of 2 tablets on day 1, then continue once daily to achieve maximal protection within 24 hours. 1, 2
• When discontinuing, continue daily dosing for 2 days after the last at-risk exposure. 1
• 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

For cisgender women, transgender women, and other populations:

• Start with the standard single-tablet dose (300mg/200mg) once daily—a loading dose is not recommended. 1, 2
• Full protective effect requires approximately 7 days of daily dosing before efficacy is achieved. 1, 2
• Daily dosing is mandatory because tenofovir concentrations in vaginal tissue are roughly ten-fold lower than in rectal tissue, and drug clearance is faster; therefore, on-demand "2-1-1" dosing is not advised. 1, 2, 4
• When discontinuing, continue daily dosing for 7 days after the last at-risk exposure. 1

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, 5
• TAF/FTC lacks efficacy data for receptive vaginal sex and should NOT be used as first-line for cisgender women. 1, 2, 5

Pre-Initiation Testing Requirements

Before prescribing PrEP, obtain the following tests: 1, 2, 5

• Combined fourth-generation HIV antibody/antigen test (within 7 days before starting)
• HIV RNA test if acute infection is suspected or high-risk exposure within the past month
• Serum creatinine with calculated creatinine clearance (TDF-based PrEP is contraindicated when clearance is <60 mL/min/1.73 m²)
• Hepatitis B surface antigen (HBsAg) and hepatitis C antibody
• Nucleic acid amplification testing (NAAT) for gonorrhea and chlamydia at all contact sites
• Syphilis testing
• Pregnancy test for individuals of childbearing potential

Monitoring Schedule During PrEP Use

Every 3 months: 1, 2, 5

• Combined HIV antibody/antigen test
• STI screening (gonorrhea, chlamydia, syphilis) at all contact sites
• Pregnancy testing for individuals of childbearing potential
• Adherence assessment and risk-reduction counseling

Renal function monitoring: 1, 2

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

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, 5

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, 5
• Monitor closely with ALT/AST testing after discontinuation. 5

Critical Safety Considerations

• Never prescribe PrEP without first confirming HIV-negative status, as inadvertent use in an HIV-positive person can select for drug-resistant virus (typically M184V/I mutation). 2
• PrEP does not protect against other sexually transmitted infections—condoms remain recommended for all penetrative sex acts. 1, 4

Bacterial STI Prevention: Doxycycline Post-Exposure Prophylaxis (DoxyPEP)

Recommended Regimen

• Doxycycline 200mg taken within 72 hours after condomless sex is recommended for cisgender MSM and transgender women, regardless of HIV status. 1, 2
• Dosing must not exceed once daily. 1, 2
• Prescribe 30 doses (60 tablets/capsules) at a time. 1, 2

Population-Specific Considerations

• For cisgender women at risk: Pharmacokinetic modeling suggests possible efficacy for vaginal exposures; therefore, consider case-by-case use. 1, 2
• Quarterly STI screening of contact sites and blood syphilis testing is recommended for all individuals using DoxyPEP. 1, 2

Comprehensive Prevention Strategy

Condoms remain a cornerstone of prevention for all penetrative sex acts to reduce acquisition of STIs, including HIV. 1

Additional prevention services should include: 1

• Risk-reduction counseling
• PrEP medication adherence counseling
• Ready access to condoms
• STI treatment when indicated by screening tests