Absolute Contraindications for Starting PrEP by Medication
The only absolute contraindication shared across all PrEP medications is confirmed HIV-positive status, while each agent has specific additional contraindications based on its pharmacology and safety profile.
TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine)
TDF/FTC is absolutely contraindicated in patients with creatinine clearance <60 mL/min 1, 2, 3. This threshold is critical because TDF is principally eliminated by the kidney and has been associated with proximal renal tubulopathy and acute renal failure 3.
Additional absolute contraindications include:
- Confirmed HIV-positive status - HIV testing with combination antigen-antibody assay is mandatory before initiation 1, 3
- Known hypersensitivity to tenofovir disoproxil fumarate or emtricitabine 3
- Unconfirmed HIV status - PrEP must not be prescribed if acute HIV infection cannot be ruled out 3, 4
Critical Pitfall to Avoid
The FDA label explicitly states that TDF/FTC for HIV-1 PrEP is "not recommended" (effectively contraindicated) in uninfected individuals with estimated creatinine clearance less than 60 mL/min 3. This is a hard stop - do not dose-adjust TDF/FTC for PrEP in renal impairment as you would for HIV treatment 3.
TAF/FTC (Tenofovir Alafenamide/Emtricitabine)
TAF/FTC has fewer absolute contraindications than TDF/FTC due to its improved renal and bone safety profile 5, 6. However, critical restrictions exist:
- Confirmed HIV-positive status 7, 8
- Known hypersensitivity to tenofovir alafenamide or emtricitabine
- Use in individuals with receptive vaginal sex as their primary exposure - TAF/FTC is only validated for cisgender men and transgender women having receptive anal sex 7, 8
- Use in people who inject drugs alone - TAF/FTC has not been studied in this population 8
Important Nuance
While TAF has better renal safety than TDF, there is no established creatinine clearance cutoff for absolute contraindication with TAF/FTC 9, 5. However, the lack of efficacy data in women and people who inject drugs makes it effectively contraindicated in these populations 8.
Cabotegravir (Long-Acting Injectable)
The FDA label provides three explicit absolute contraindications for cabotegravir 10:
- Previous hypersensitivity reaction to cabotegravir 10
- Coadministration with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine - these potent enzyme inducers significantly reduce cabotegravir levels 10
- Positive HIV-1 status 10
Key Clinical Consideration
Unlike oral PrEP where drug interactions can sometimes be managed, the long-acting nature of injectable cabotegravir makes concurrent use with strong CYP3A inducers an absolute contraindication - you cannot simply "hold" the injection 10.
Lenacapavir
No FDA-approved labeling for lenacapavir as PrEP exists as of the evidence provided. Lenacapavir is currently approved only for HIV treatment in heavily treatment-experienced patients, not for prevention [@Evidence not provided in search results@]. Therefore, absolute contraindications for PrEP use cannot be definitively stated from available guidelines.
Universal Contraindication Across All PrEP Agents
Unconfirmed HIV-negative status is an absolute contraindication for all PrEP medications 1, 2, 10, 3. This requires:
- Combination HIV antigen-antibody testing at initiation 1, 2
- HIV RNA testing if acute infection is suspected based on symptoms or recent high-risk exposure 1, 2
- Recognition that starting PrEP during undiagnosed acute HIV infection can lead to drug resistance 4
Critical Diagnostic Pitfall
PrEP users who seroconvert present with lower viral load peaks and fewer symptoms than individuals not on PrEP, and PrEP prolongs the stages of seroconversion, potentially complicating diagnosis 4. This makes careful exclusion of acute HIV infection before starting PrEP absolutely crucial 4.
Special Population Considerations
Active hepatitis B infection with cirrhosis requires careful consideration but is not an absolute contraindication 1. However, discontinuation of TDF/FTC or TAF/FTC in patients with active HBV (detectable HBsAg) can lead to acute hepatitis flares or hepatic decompensation 1, 2. For these patients, careful monitoring after discontinuation is mandatory rather than avoiding PrEP entirely 1.
Pregnancy and breastfeeding are not contraindications to any PrEP medication 7. TDF/FTC is safe during pregnancy and breastfeeding, and long-acting cabotegravir has a growing safety profile in these populations 7.