What are the recommended regimens and monitoring for HIV pre‑exposure prophylaxis (PrEP) and post‑exposure prophylaxis (PEP)?

HIV Prophylaxis: PrEP and PEP Regimens and Monitoring

For HIV pre-exposure prophylaxis (PrEP), use daily oral TDF/FTC as first-line for most patients, long-acting injectable cabotegravir for those who prefer injections or struggle with daily adherence, and initiate immediately with rapid start protocols while awaiting confirmatory testing. For post-exposure prophylaxis (PEP), prescribe a 3-drug regimen (dolutegravir plus TDF/FTC or bictegravir/TAF/FTC) within 72 hours of exposure for 28 days, then transition seamlessly to PrEP if ongoing risk exists 1, 2.

Pre-Exposure Prophylaxis (PrEP)

Recommended Regimens

Oral PrEP Options:

• TDF/FTC (tenofovir disoproxil fumarate/emtricitabine): First-line for all populations including cisgender women, transgender women, men who have sex with men, and people who inject drugs 1, 2

  • Daily dosing: One tablet daily
  • On-demand "2-1-1" dosing: Only for cisgender men and transgender women for anal sex exposures (2 tablets 2-24 hours before sex, 1 tablet 24 hours after first dose, 1 tablet 48 hours after first dose). Continue daily dosing until 2 doses after last sexual activity 1
  • Critical caveat: Transgender women using gender-affirming hormones must take 2-1-1 dosing WITH FOOD due to lower rectal tissue drug concentrations 1
  • Do NOT use on-demand dosing for vaginal exposures or injection drug use alone—insufficient data 1

• TAF/FTC (tenofovir alafenamide/emtricitabine): Daily dosing only

  • Restrict to: Cisgender men and others WITHOUT receptive vaginal sex (including neovaginal sex) or injection drug use alone as sole exposure 1
  • Preferred for: Creatinine clearance 30-60 mL/min, known osteopenia/osteoporosis 1

Injectable PrEP:

• Long-acting cabotegravir: 600 mg (3 mL) gluteal injections—first 2 injections 4 weeks apart, then every 8 weeks 1
  • Best for: Patients who prefer injections or cannot adhere to daily oral medications 1
  • Oral lead-in (4-5 weeks) is OPTIONAL, but recommended only for severe atopic histories or patient request—NOT recommended for those with adherence challenges 1
  • Mandatory 7-day overlap: Continue oral PrEP (cabotegravir tablets or TDF/FTC) for 7 days after first injection 1
  • Patients must keep 1-month supply of oral TDF/FTC for bridging if injection delayed ≥7 days 1

Rapid PrEP Start Protocol

Initiate PrEP immediately if:

• Negative HIV test within past 7 days OR negative rapid test same day 1
• No signs/symptoms of acute HIV infection 1
• Can start remotely once baseline HIV test confirmed negative 1

If substantial exposure within past 72 hours: Start 3-drug PEP regimen first for 28 days, then transition to PrEP if HIV test (antigen/antibody AND RNA) negative at PEP completion 1

Baseline and Monitoring Requirements

Before Starting PrEP:

• HIV testing (antigen/antibody immunoassay preferred; rapid test acceptable) 1, 3
• Creatinine clearance assessment 1
• Hepatitis B and C screening 2
• Sexually transmitted infection (STI) screening 2, 4
• Pregnancy test if applicable 4
• Bone density scans NOT necessary before starting tenofovir-based PrEP 1

Follow-up Every 3 Months:

• HIV testing (antigen/antibody or RNA) 1, 3, 4
• STI screening 4
• Assess adherence and side effects 4
• Renal function monitoring (creatinine clearance) 4
• Pregnancy testing if applicable 4

Post-Exposure Prophylaxis (PEP)

When to Prescribe PEP

Initiate within 72 hours of exposure when:

• Source person likely has transmissible HIV (unknown status, known positive not virally suppressed) 2, 5
• Biologically significant exposure occurred (receptive/insertive anal/vaginal sex, needlestick, shared injection equipment) 2, 5

Earlier initiation is critical: Modeling shows 2-drug PEP may fail if started >1 hour post-exposure; 3-drug regimens maintain >90% efficacy when started within 48 hours 6

Recommended PEP Regimens

Preferred 3-drug regimens for 28 days:

• Dolutegravir plus TDF/FTC 2
• Bictegravir/TAF/FTC (single-tablet regimen) 2

Duration: 28 days is standard, though modeling suggests 14-28 days may suffice with 3-drug regimens if started early 6

PEP Monitoring

Baseline (before or at PEP initiation):

• HIV testing (antigen/antibody plus RNA if available) 1, 5
• Hepatitis B and C screening 5
• Renal function 5
• Pregnancy test if applicable 5

Follow-up:

• HIV testing at 4-6 weeks and 3 months post-exposure 5
• Monitor for seroconversion symptoms 5
• Assess adherence and side effects 5

Seamless PEP-to-PrEP Transition

If ongoing HIV risk exists after PEP completion:

• Perform HIV test (antigen/antibody AND RNA) at day 28 1
• If negative, transition immediately to appropriate PrEP regimen without gap 1
• This prevents the vulnerable window between PEP completion and PrEP initiation

Special Considerations

PrEP-to-PEP Transitions:

• Recent PrEP use enhances PEP efficacy by maintaining drug concentrations and delaying viral dynamics 6
• Self-starting TDF/FTC immediately after exposure (even before accessing third drug) is better than waiting 6

Pregnancy and Breastfeeding:

• PrEP and PEP are safe and recommended during pregnancy and lactation 5, 4
• TDF/FTC is the preferred backbone 4

Chronic Hepatitis B:

• Use TDF-containing regimens when possible (treats both HIV prophylaxis and HBV) 5
• Monitor for HBV flare if discontinuing tenofovir 5

Critical Pitfalls to Avoid

1. Delaying PrEP start: Any delay is a missed prevention opportunity—use rapid start protocols 1
2. Wrong PrEP regimen for exposure type: Never use TAF/FTC for vaginal exposures or on-demand dosing for vaginal/IDU exposures 1
3. Missing the 72-hour PEP window: Emphasize to patients that immediate presentation after exposure is critical 5, 6
4. Inadequate PEP regimen: Always use 3-drug regimens; 2-drug PEP has insufficient efficacy 2, 6
5. Gap between PEP and PrEP: Transition seamlessly without interruption if ongoing risk 1
6. Forgetting injection overlap: Must continue oral PrEP for 7 days after first cabotegravir injection 1