What is the recommended preexposure prophylaxis (PrEP) regimen for individuals at high risk of Human Immunodeficiency Virus (HIV) infection and other Sexually Transmitted Infections (STIs)?

Pre-Exposure Prophylaxis (PrEP) for HIV and STI Prevention

The recommended PrEP regimen for individuals at high risk of HIV infection is daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada) as the standard first-line option, with specific alternatives available for certain populations based on risk factors and medical conditions. 1

First-Line PrEP Options

• Daily oral TDF/FTC (300mg/200mg) is the standard recommended PrEP regimen with proven efficacy across all risk groups including men who have sex with men (MSM), heterosexual men and women, and people who inject drugs 1, 2
• For individuals with or at risk for kidney dysfunction, osteopenia, or osteoporosis, daily tenofovir alafenamide/emtricitabine (TAF/FTC, Descovy) is recommended as an alternative, but only for MSM and transgender women 1, 3
• On-demand (2-1-1) dosing of TDF/FTC is an acceptable alternative specifically for cisgender men having planned receptive anal sex, but is not recommended for other populations 2, 1

Population-Specific Considerations

For MSM and Transgender Women:

• Both TDF/FTC and TAF/FTC are effective options 1, 3
• TAF/FTC is specifically indicated for those with or at risk for kidney dysfunction, osteopenia, or osteoporosis 3
• On-demand dosing (2-1-1) can be considered for those with infrequent sexual exposures 2

For Cisgender Women and Heterosexual Men:

• Daily TDF/FTC is the only recommended option with proven efficacy 4
• Daily dosing is critical for women as tenofovir concentrates at 10-fold lower levels in vaginal tissue than in rectal tissue 4
• TAF/FTC is NOT currently recommended for cisgender women or prevention of HIV from receptive vaginal sex 3

For People Who Inject Drugs:

• Daily TDF/FTC is the recommended regimen 2, 1

Pre-Initiation Testing Requirements

Before starting PrEP, the following tests must be performed:

• Combined HIV antibody and antigen testing (to rule out existing HIV infection) 1, 2
• Serum creatinine level and estimated creatinine clearance (≥60 mL/min required) 2, 1
• Hepatitis B surface antigen (HBsAg) testing 2, 1
• Hepatitis C antibody testing 2, 1
• Comprehensive STI screening including genital and non-genital Neisseria gonorrhoeae and Chlamydia trachomatis testing 1, 2
• Pregnancy testing for individuals of childbearing potential 2, 1

Dosing and Administration

For TDF/FTC (Truvada):

• Standard dosage: One tablet (TDF 300mg/FTC 200mg) taken orally once daily 2, 1
• For MSM, maintain daily dosing 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 on-demand (2-1-1) dosing (MSM only): Take 2 pills 2-24 hours before sex, then 1 pill 24 hours after the first dose, and 1 pill 24 hours after the second dose 2, 1

For TAF/FTC (Descovy):

• Standard dosage: One tablet (TAF 25mg/FTC 200mg) taken orally once daily 3
• Unlike TDF/FTC, there is no recommendation for a double loading dose when starting TAF/FTC 3
• TAF/FTC should be taken daily for continued protection, not on an event-driven or "2-1-1" dosing schedule 3

Monitoring Recommendations

• HIV testing at 1 month after initiation and quarterly thereafter 1, 2
• Creatinine clearance at first quarterly visit and annually thereafter (more frequently for those with risk factors for kidney disease) 1, 2
• STI testing quarterly, even if asymptomatic 2, 1
• Risk behavior assessment and risk-reduction counseling at each visit 2
• PrEP prescriptions should not exceed 90 days without interval testing for HIV infection 2

Important Caveats and Considerations

• PrEP does not prevent other sexually transmitted infections; condoms should still be encouraged 2, 1
• PrEP should be delivered as part of a comprehensive set of prevention services, including risk-reduction counseling and ready access to condoms 2
• If HIV infection is suspected or confirmed while on PrEP, the medication should be stopped immediately and resistance testing performed 2
• For individuals with active hepatitis B infection, discontinuation of TDF/FTC could lead to acute hepatitis B flares; careful monitoring is required 2
• Seroconversion while on PrEP is rare but can occur; any positive HIV screening test result should prompt immediate confirmatory testing with HIV RNA and genotype testing 2

By following these evidence-based guidelines for PrEP, healthcare providers can significantly reduce the risk of HIV acquisition in high-risk individuals while also addressing potential concerns related to STIs, medication adherence, and long-term safety.