HIV Pre-Exposure Prophylaxis (PrEP): Indications and Contraindications
Primary Recommendation
PrEP with daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) should be offered to all HIV-negative individuals at substantial risk of HIV acquisition, with same-day initiation reasonable after confirming HIV-negative status by rapid testing. 1, 2
Indications for PrEP
Men Who Have Sex with Men (MSM)
Daily oral PrEP is indicated for MSM with any of the following risk factors: 1, 3
- Condomless anal intercourse in the past 6 months
- STI diagnosis in the past 6 months
- Sexual partner(s) with known HIV infection
- Use of post-exposure prophylaxis (PEP) more than once in the preceding 12 months 1
- Transactional sex or multiple sexual partners 1
Heterosexual Men and Women
PrEP should be considered for heterosexuals with: 1
- At least one episode of condomless vaginal intercourse with two or more partners in the past 6 months
- STI diagnosis in the past 6 months
- Sex work or transactional sex engagement
- Use of nPEP more than once in the preceding 12 months
People Who Inject Drugs (PWID)
Daily oral PrEP is indicated for PWID who share injection equipment or have other HIV risk factors. 1
Serodiscordant Couples
PrEP is strongly indicated for the HIV-negative partner in serodiscordant relationships, particularly when the HIV-positive partner is not virologically suppressed. 4
Absolute Contraindications
HIV Infection Status
- Do not prescribe PrEP if HIV infection is confirmed or suspected. 1, 3
- Defer PrEP initiation if signs/symptoms of acute HIV infection are present (fever, headache, muscle soreness, sore throat, rash, swollen lymph nodes) until HIV is definitively excluded. 1, 5
- If acute HIV is suspected clinically, obtain HIV RNA testing in addition to combination antigen-antibody testing before starting PrEP. 1, 5
Renal Dysfunction
- Do not prescribe TDF-based PrEP if creatinine clearance is <60 mL/min. 3
- For MSM with creatinine clearance 30-60 mL/min, use tenofovir alafenamide/emtricitabine (TAF/FTC, Descovy) instead. 3, 6
Relative Contraindications and Special Precautions
Bone Disease
- For MSM with osteopenia or osteoporosis, prescribe TAF/FTC (Descovy) rather than TDF/FTC. 3, 6
- Critical limitation: TAF/FTC is NOT approved for cisgender women or event-driven "2-1-1" dosing. 3
Hepatitis B Infection
- Do not use "2-1-1" (on-demand) PrEP dosing in patients with active HBV infection due to risk of hepatitis flare and hepatic decompensation. 7
- Never discontinue TDF/FTC abruptly in patients with chronic HBV without close monitoring and transition planning, as this can precipitate hepatic decompensation. 7, 3
- Liver disease with cirrhosis (Child-Pugh class B or C) may require dosage modifications or alternative regimens. 7
Hepatitis C Infection
- More frequent monitoring of liver transaminases is required for patients with HCV infection or HBV/HCV co-infection. 7
- Consult specialists when patients are on direct-acting antiviral (DAA) agents, as DAAs can reactivate HBV. 7
Pregnancy
- PrEP can be prescribed during pregnancy after thorough discussion of risks and benefits, as no statistically significant differences in pregnancy outcomes, miscarriage, or adverse birth outcomes have been demonstrated. 1
- Ensure the HIV-positive partner in serodiscordant couples achieves viral suppression as early as possible. 1
Mandatory Pre-Initiation Testing
Before prescribing PrEP, obtain the following tests: 1, 3
- HIV testing: Combined antibody-antigen assay (4th generation); add HIV RNA if acute infection suspected
- Renal function: Serum creatinine and estimated creatinine clearance
- Hepatitis B: Surface antigen (HBsAg) testing is mandatory 7
- Hepatitis C: IgG antibody (if not previously positive)
- Hepatitis A: IgG antibody for MSM and PWID (if not immune) 1
- STI screening: Three-site NAAT testing (rectal, pharyngeal, urogenital) for gonorrhea and chlamydia in MSM 1, 3
- Pregnancy test: For women of childbearing age 1
Initiating PrEP without baseline HBsAg testing significantly increases hepatotoxicity risk and should be avoided. 7
Ongoing Monitoring Requirements
Quarterly (Every 3 Months)
- HIV testing with combined antigen-antibody assay 1, 3
- Three-site STI screening (MSM) 3
- Clinical assessment of adherence and risk behaviors 1
Every 6-12 Months
- Serum creatinine and estimated glomerular filtration rate 3
- More frequent renal monitoring (every 3-6 months) for patients >50 years, taking hypertension/diabetes medications, or with baseline eGFR <90 mL/min 3
For Hepatitis C Risk
- HCV serologic testing at least annually, more frequently with elevated transaminases or in high-risk individuals (e.g., PWID) 7
For Injectable Cabotegravir PrEP
- Liver enzyme tests every 6 months 7
PrEP prescription should not exceed 90 days without interval HIV testing. 1
Medication Selection Algorithm
First-Line for Most Populations
- Daily oral TDF/FTC (Truvada): Standard regimen for all populations 1, 3
- For MSM: Double dose (2 pills) on first day, then 1 pill daily 1
- Continue for 1 week after last sexual exposure when discontinuing 3
- Requires 1-week lead-in period for adequate tissue levels 3
Alternative Regimens
- TAF/FTC (Descovy): For MSM with renal impairment (CrCl 30-60 mL/min), osteopenia, or osteoporosis 3, 6
- "2-1-1" on-demand dosing: Only for MSM without HBV infection (2 pills 2-24 hours before sex, 1 pill 24 hours after first dose, 1 pill 48 hours after first dose) 1, 7
- Injectable cabotegravir every 8 weeks: For cisgender men and transgender women who have sex with men (pending regulatory approval) 1
Management of HIV Seroconversion During PrEP
If HIV infection is diagnosed or suspected while on PrEP: 1, 3, 5
- Immediately stop PrEP and add a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat) and/or dolutegravir to TDF/FTC while awaiting confirmatory testing
- Obtain HIV RNA and genotype resistance testing urgently 1
- Switch to a recommended initial antiretroviral regimen once HIV is confirmed 3
- Resistance (typically M184V/I mutation) is rare but can occur when PrEP is initiated during undiagnosed acute HIV infection 1, 5
Primary HIV infection in PrEP users presents with lower viral load peaks, fewer symptoms, and prolonged seroconversion stages, potentially complicating diagnosis. 5
Common Pitfalls to Avoid
- Never prescribe PrEP without confirming HIV-negative status first 1, 3
- Never use TAF/FTC for cisgender women—it is not approved for this population 3
- Never use "2-1-1" dosing in patients with HBV infection 7
- Never discontinue TDF/FTC abruptly in HBV-positive patients 7, 3
- Never exceed 90 days between HIV testing intervals 1
- Avoid unanticipated interruptions in PrEP delivery (insurance lapses, incarceration, relocation), as these are associated with seroconversions 1