What are the recommended HIV pre‑exposure prophylaxis (PrEP) and post‑exposure prophylaxis (PEP) regimens, baseline testing, monitoring schedule, and alternative options?

HIV Prophylaxis: PrEP and PEP Regimens, Testing, and Monitoring

For pre-exposure prophylaxis (PrEP), use daily oral TDF/FTC as the first-line regimen for all populations, long-acting injectable cabotegravir every 8 weeks for those at risk through sexual exposures, or TAF/FTC for cisgender men without receptive vaginal exposure; for post-exposure prophylaxis (PEP), initiate bictegravir/emtricitabine/tenofovir alafenamide within 72 hours (ideally within 24 hours) and continue for 28 days. 1, 2

Pre-Exposure Prophylaxis (PrEP) Regimens

Oral PrEP Options

Daily TDF/FTC (tenofovir disoproxil fumarate 300mg/emtricitabine 200mg) is the primary recommended oral PrEP regimen for all populations at risk of HIV acquisition, including people who inject drugs, cisgender women, and transgender women. 1

• For cisgender men having sex with men (MSM): Start with a double dose (2 tablets) on day one to achieve protective drug levels more rapidly, then continue once daily. 1
• Efficacy exceeds 90% when adherence is maintained, but effectiveness is highly correlated with adherence. 3
• Time to protection: Daily TDF/FTC requires 7 days of consecutive dosing to reach protective levels in rectal tissue and 20 days for vaginal tissue. 1

On-demand (2-1-1) dosing with TDF/FTC is recommended specifically for cisgender men and others having planned receptive anal sex (but NOT for receptive vaginal sex or injection drug use exposures). 1

• Take 2 tablets 2-24 hours before sex, then 1 tablet 24 hours after the first dose, and 1 tablet 48 hours after the first dose.
• If additional sexual activity occurs, continue daily single dosing until 2 doses after the last activity.
• Critical caveat: Transgender women using gender-affirming hormone therapy should take 2-1-1 dosing WITH FOOD because rectal tissue concentrations may be lower early after starting, which food intake largely mitigates. 1

Daily TAF/FTC (tenofovir alafenamide 25mg/emtricitabine 200mg) should be limited to cisgender men and others whose exposures do NOT include receptive vaginal sex (including neovaginal sex) or injection drug use alone. 1

• Preferred for: Individuals with creatinine clearance 30-60 mL/min, known osteopenia or osteoporosis. 1
• TAF offers superior renal and bone safety compared to TDF. 2
• Bone density scans are NOT necessary before initiating tenofovir-based PrEP. 1

Injectable PrEP

Long-acting cabotegravir 600mg intramuscular injections are recommended for people at risk of HIV through sexual exposures. 1

• Dosing schedule: First 2 injections separated by 4 weeks, then every 8 weeks thereafter by gluteal administration.
• Oral lead-in: Optional for 4-5 weeks, but recommended for those with severe atopic histories or who request it; NOT recommended for those who struggle with daily oral adherence. 1
• Overlap strategy: Continue or initiate exposure-appropriate oral PrEP for 7 days after the first injection to allow time for maximal protection. 1
• Backup supply: Provide a 1-month supply of appropriate oral PrEP for bridging if injection delays occur ≥7 days. 1
• For people who inject drugs (PWID): Recommended if they also have sexual HIV exposure risk. 1

Rapid PrEP Initiation

Start PrEP immediately without delay—any delay is a missed prevention opportunity. 1

• If negative HIV test results are available from blood drawn within 7 days OR a rapid HIV antibody test is negative on the day of initiation, start PrEP while awaiting additional diagnostics. 1
• PrEP may be initiated remotely once baseline HIV tests are confirmed negative. 1
• If substantial HIV exposure occurred within the past 72 hours: Use a 3-drug PEP regimen for 28 days, then transition seamlessly to PrEP if HIV testing (antigen/antibody AND RNA) at PEP completion is negative. 1

Baseline Testing Before PrEP Initiation

Perform the following tests before or immediately at PrEP start: 1

• Combined HIV antibody/antigen test (fourth-generation); add HIV RNA if acute HIV infection is suspected clinically.
• Serum creatinine to calculate creatinine clearance.
• Hepatitis B surface antigen (HBsAg).
• Hepatitis C antibody (if not previously positive; confirm HCV RNA if known positive).
• Hepatitis A antibody for MSM and PWID (if immunity unknown).
• Gonorrhea and chlamydia NAAT from all exposed sites (genital, rectal, pharyngeal as appropriate).

Do NOT delay PrEP initiation while awaiting these results if HIV testing is negative. 1

Monitoring During PrEP

At 1 Month

• Combined HIV antibody/antigen test. 1

Every 3 Months (Quarterly)

• Combined HIV antibody/antigen test. 1
• Estimated creatinine clearance at first quarterly visit, then annually thereafter (or more frequently if creatinine clearance <60 mL/min). 1
• STI screening (gonorrhea/chlamydia NAAT from exposed sites). 1
• Pregnancy test for individuals who can become pregnant. 1

Every 6-12 Months

• Hepatitis C antibody (if ongoing risk). 1

Post-Exposure Prophylaxis (PEP) Regimens

Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg once daily for 28 days is the preferred first-line PEP regimen because of superior renal and bone safety. 2

Alternative regimen: Dolutegravir 50mg once daily plus emtricitabine 200mg/tenofovir alafenamide 25mg once daily for 28 days. 2

• If TAF is unavailable, tenofovir disoproxil fumarate 300mg may be substituted, but TAF is strongly preferred. 2

Timing of PEP Initiation

Start PEP as soon as possible, ideally within 24 hours and no later than 72 hours after exposure—effectiveness declines sharply with each hour of delay. 2

• Do NOT wait for risk assessment or source testing; start immediately with any available antiretrovirals. 2
• Complete the full 28-day course regardless of subsequent source information; incomplete adherence markedly reduces efficacy. 2

Baseline Assessment for PEP

Perform before or immediately after starting PEP: 2

• Fourth-generation HIV antigen/antibody test (rapid or laboratory-based).
• Add HIV nucleic acid test (NAT) if the exposed person received long-acting injectable PrEP within the past 12 months.
• Evaluate: Comorbidities, allergies, drug-drug interactions, baseline renal function (creatinine clearance).
• Screen for other STIs at baseline.
• Test the source for HIV with rapid test when feasible, but do NOT delay PEP.

PEP Follow-Up Testing Schedule

Time Point	Tests	Purpose
≤72 hours after start	Clinical evaluation	Early safety monitoring [2]
4-6 weeks	Fourth-generation HIV Ag/Ab + HIV NAT	Detect early seroconversion [2,4]
12 weeks (3 months)	Fourth-generation HIV Ag/Ab + HIV NAT	Definitive confirmation of negative status [2,4]

• Extended follow-up to 12 months is recommended for healthcare workers co-infected with HCV after exposure to a source with both HIV and HCV. 2, 5
• Test immediately if acute retroviral syndrome symptoms develop (fever, rash, lymphadenopathy) regardless of timeline. 2, 5

Indications for PEP

Offer PEP for: 2

• Percutaneous injuries (needlestick, sharp injuries) with blood or potentially infectious fluids.
• Mucous membrane exposures to blood, semen, vaginal/rectal secretions, or breast milk.
• Non-intact skin contact with the above fluids.
• Exposure to: Cerebrospinal, amniotic, peritoneal, synovial, pericardial, or pleural fluids.

Do NOT offer PEP for: 2

• Exposure to non-infectious fluids (tears, non-bloody saliva, urine, feces, vomitus, sputum, nasal secretions, sweat).
• Exposed person is already HIV-positive.
• Source is confirmed HIV-negative with no recent risk factors.

Transition from PEP to PrEP

For persons with anticipated repeat or ongoing HIV exposures, transition immediately from PEP to PrEP after completing the 28-day course. 2

• Perform HIV testing at the end of PEP before initiating PrEP to confirm seronegative status. 2

Special Populations

Renal Impairment

• Use TAF rather than TDF for any degree of renal dysfunction; TAF has minimal renal toxicity. 2

Pregnancy and Breastfeeding

• Pregnancy does NOT contraindicate optimal PrEP or PEP regimens; decisions should be made jointly with the patient. 2
• Do NOT withhold PrEP or PEP from pregnant or breastfeeding individuals; expert consultation is advised but should not be a prerequisite. 2

Common Pitfalls to Avoid

• Do NOT delay PrEP or PEP while awaiting source testing or detailed risk assessment—start immediately. 1, 2
• Do NOT use two-drug regimens for PEP unless no three-drug options are available. 2
• Do NOT discontinue PEP early based on later source information; complete the full 28 days. 2
• Do NOT test discarded needles or syringes for HIV; this is unreliable and delays care. 2
• Do NOT assume on-demand PrEP works for vaginal exposures or injection drug use—it is only validated for receptive anal sex in cisgender men. 1
• Provide antiemetics proactively to mitigate nausea and support adherence during PEP. 2