What is the most appropriate HIV prevention intervention for a high-risk, HIV-negative man who has sex with men (MSM) and meets new partners at nightclubs, assuming he already uses condoms?

Recommended HIV Prevention Intervention for High-Risk MSM

Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) as PrEP with HIV testing every 3 months is the most appropriate intervention for this patient. 1

Rationale for TDF/FTC Combination

• TDF/FTC is the gold standard PrEP regimen with the highest level of evidence (AIa) for MSM populations, demonstrating over 90% efficacy when adherence is maintained. 1, 2

• The combination of both agents is specifically recommended over TDF monotherapy for sexual HIV prevention, as this is the FDA-approved regimen with proven efficacy in the iPrEx trial showing 44% overall risk reduction in MSM (exceeding 90% with good adherence). 1, 2, 3

• For MSM specifically, guidelines recommend starting with a double dose (2 pills) of TDF/FTC on the first day, followed by daily dosing. 1, 4

Why Not the Other Options

TDF Monotherapy (Option 2 & 3)

• TDF alone is not recommended for PrEP in MSM. 1 While TDF monotherapy showed efficacy in people who inject drugs and heterosexual couples, the FDA-approved and guideline-recommended regimen for sexual HIV prevention is the TDF/FTC combination. 1, 3

Zidovudine/Lamivudine (Option 4)

• This combination has no evidence base for PrEP and is not recommended. 1 No clinical trials have evaluated zidovudine-based regimens for pre-exposure prophylaxis.

TAF/FTC Alternative

• While tenofovir alafenamide/emtricitabine (TAF/FTC) is an acceptable alternative, it is specifically reserved for MSM with or at risk for kidney dysfunction, osteopenia, or osteoporosis (evidence rating BIa). 1, 4 Since this patient has no mentioned renal or bone concerns, TDF/FTC remains first-line.

HIV Testing Frequency: Every 3 Months is Standard

• Quarterly (every 3 months) HIV testing with combined antibody/antigen assay is the evidence-based monitoring interval (AIa evidence rating). 1, 5

• Monthly HIV testing (as suggested in options 2 and 3) is not standard of care and represents unnecessary healthcare utilization without added benefit. 1

• The only exception is an optional 1-month follow-up visit after initiation to assess adherence and rule out acute HIV infection that may have been in the window period at baseline (BIII evidence). 1

Critical Implementation Details

Pre-Initiation Requirements

• Combined HIV antibody and antigen testing must be performed within 7 days before starting PrEP to exclude HIV infection. 1, 5 If acute HIV infection is suspected clinically, an HIV RNA test is required before initiation. 1

• Additional baseline testing includes: serum creatinine with calculated creatinine clearance (must be ≥60 mL/min for TDF/FTC), hepatitis B surface antigen, hepatitis C antibody, and comprehensive STI screening (genital and nongenital gonorrhea/chlamydia by NAAT, syphilis testing). 1, 4

Ongoing Monitoring Every 3 Months

• Combined HIV antibody/antigen testing 1
• Three-site STI screening (urethral/rectal/pharyngeal for MSM) 1, 5
• Syphilis serology 1
• Adherence assessment and risk behavior counseling 5
• Creatinine clearance at first quarterly visit, then annually (more frequently if age >50 or renal risk factors) 1, 5

Common Pitfalls to Avoid

• Never prescribe PrEP for more than 90 days without interval HIV testing, as undetected HIV infection with ongoing PrEP can lead to resistance. 5

• Do not initiate PrEP if acute HIV infection is suspected clinically (fever, rash, lymphadenopathy, high-risk exposure in past 2-4 weeks) until HIV RNA confirms negative status, as antibody/antigen testing may be falsely negative during the window period. 1

• Resistance to TDF/FTC is rare (<0.1%) but almost always occurs when PrEP is inadvertently started during undiagnosed acute HIV infection. 2 This underscores the critical importance of baseline testing.

• Daily adherence is essential for efficacy. Detection of TDF in blood at levels consistent with daily use correlates with 99% risk reduction, while inconsistent use dramatically reduces protection. 1, 2 For MSM, at least 4 doses per week provides substantial protection for rectal exposures, but daily dosing is recommended to establish routine and maximize protection. 4

Alternative Dosing for MSM

• On-demand "2-1-1" dosing is an evidence-based alternative for MSM with infrequent, planned sexual encounters (AIa evidence from IPERGAY trial): 2 pills 2-24 hours before sex, 1 pill 24 hours after the first dose, and 1 pill 24 hours later. 1, 4 However, this requires careful patient selection and counseling, as it is only validated for MSM and requires planning ahead.