What is the recommended HIV prophylaxis regimen for a healthy adult with no significant medical history?

HIV Pre-Exposure Prophylaxis (PrEP) for Healthy Adults

For a healthy adult with no significant medical history at risk for HIV, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200 mg once daily is the recommended first-line oral PrEP regimen. 1

Primary Regimen Selection

• Daily oral TDF/FTC (Truvada) is the standard PrEP regimen with the strongest evidence base (AIa rating) for all at-risk populations including men who have sex with men (MSM), heterosexual men and women, and people who inject drugs 1, 2

• For MSM specifically, a double loading dose (2 tablets) on the first day is recommended to achieve maximal protection within 24 hours, followed by one tablet daily thereafter 1, 2

• Tenofovir alafenamide/emtricitabine (TAF/FTC, Descovy) 25/200 mg once daily is an alternative specifically for MSM with or at risk for kidney dysfunction (creatinine clearance 30-60 mL/min), osteopenia, or osteoporosis (BIa rating) 1, 3

Alternative Dosing Strategy for MSM

• Event-driven "2-1-1" PrEP dosing is recommended only for MSM: 2 tablets of TDF/FTC taken 2-24 hours before sexual activity, then 1 tablet 24 hours later, and 1 tablet 24 hours after that (AIa rating) 1, 2

• This on-demand approach is not recommended for cisgender women or with TAF/FTC formulations 3, 2

Mandatory Pre-Initiation Testing

Before starting PrEP, the following tests are required:

• Combined HIV antibody and antigen testing (fourth-generation assay preferred); if acute HIV infection is suspected clinically, HIV RNA testing must be performed and results confirmed negative before initiating PrEP 1, 2

• Serum creatinine and estimated creatinine clearance to assess renal function 1, 2

• Hepatitis B surface antigen testing 1, 2

• Hepatitis C antibody testing 1

• Comprehensive STI screening including nucleic acid amplification testing (NAAT) for gonorrhea and chlamydia at genital and non-genital sites (oral, rectal, vaginal as appropriate), plus syphilis serology 1

• Hepatitis A antibody for MSM and people who inject drugs if immunity status unknown 1

Vaccination Requirements

• Hepatitis A and B vaccination for those not immune (AIII rating) 1

• Human papillomavirus (HPV) vaccination is recommended for women aged 13-26 years and men aged 13-21 years who have not completed the 3-dose series; men aged 22-26 years may be vaccinated (AIa rating) 1

Ongoing Monitoring Schedule

• HIV testing every 3 months using combined antibody/antigen assay (AIII rating) 1

• STI screening every 3 months at all relevant anatomic sites (BIIb rating) 1, 2

• Creatinine assessment at least every 6 months, potentially more frequently for patients over 50 years, those taking hypertension or diabetes medications, or those with borderline renal function (AIII rating) 1, 2

• Adherence counseling at each visit (CIII rating) 1

Critical Contraindications and Caveats

• Do not initiate PrEP in anyone with undiagnosed HIV infection or suspected acute HIV infection until HIV RNA results confirm negative status 1, 3

• TDF-based PrEP is contraindicated with creatinine clearance <60 mL/min 2

• If a patient on PrEP develops suspected HIV infection (clinically or with equivocal screening results), immediately add a boosted protease inhibitor (darunavir) and/or dolutegravir to TDF/FTC pending HIV RNA and resistance testing 1

• TAF/FTC (Descovy) is NOT recommended for cisgender women or prevention from receptive vaginal sex, as efficacy data are lacking in these populations 3

• No loading dose is used with TAF/FTC, unlike TDF/FTC for MSM 3, 2

Evidence Quality Considerations

The 2020 International Antiviral Society-USA guidelines 1 represent the most recent high-quality recommendations, superseding the 2016 guidelines 1. The DISCOVER trial 4, 5 demonstrated non-inferiority of TAF/FTC to TDF/FTC with superior bone and renal safety profiles, though this was studied primarily in MSM and transgender women. Earlier trials 6, 7 established the foundational efficacy of TDF/FTC, showing 44-75% risk reduction when adherence was maintained.

The key to PrEP success is adherence: efficacy correlates directly with medication adherence, and trials with poor adherence showed no benefit 6, 7. Regular adherence discussions are essential at every follow-up visit 1.