PrEP in Patients with CrCl <60 mL/min
TDF-based PrEP (tenofovir disoproxil fumarate/emtricitabine) is contraindicated when creatinine clearance falls below 60 mL/min/1.73 m², and you should instead prescribe tenofovir alafenamide/emtricitabine (TAF/FTC) for this patient. 1, 2
Primary Recommendation: Switch to TAF-Based PrEP
For patients with CrCl 30-59 mL/min, tenofovir alafenamide/emtricitabine is the preferred PrEP regimen because TAF has minimal renal toxicity compared to TDF and does not require dose adjustment until CrCl drops below 30 mL/min 2
The International Antiviral Society-USA Panel explicitly states that TDF-based PrEP is not recommended in persons with creatinine clearance below 60 mL/min/1.73 m² (evidence rating AIIa) 1
The CDC specifically recommends considering TAF/emtricitabine instead of TDF/FTC for men who have sex with men with CrCl 60-89 mL/min or other renal risk factors 2
Why TDF is Contraindicated in This Population
TDF is eliminated unchanged in urine with significant active tubular secretion, making it particularly nephrotoxic in patients with pre-existing renal dysfunction 1, 3
The FDA label for emtricitabine (component of TDF/FTC) requires dose interval adjustment for CrCl 30-49 mL/min (every 48 hours instead of daily) and contraindicates the combination tablet for CrCl <30 mL/min 4
Tenofovir pharmacokinetic studies demonstrate that patients with CrCl <50 mL/min have substantially reduced renal clearance and increased drug exposures, necessitating dose-interval adjustments 3
In HIV treatment settings (not PrEP), tenofovir can be used with close monitoring and dose adjustment in patients with CrCl 30-49 mL/min, but this approach has not been validated for PrEP and carries significant risk of proximal tubular dysfunction 1, 5
Critical Pre-Initiation Steps
Calculate creatinine clearance using the Cockcroft-Gault equation before making any PrEP prescribing decision 2
Perform mandatory HIV antibody/antigen testing (4th generation) to confirm HIV-negative status—this must be negative before starting any PrEP regimen 1, 6
Add HIV RNA testing if any clinical suspicion of acute HIV infection exists (fever, rash, lymphadenopathy, pharyngitis) because initiating PrEP during undiagnosed acute HIV can lead to drug resistance 6
Test for hepatitis B surface antigen (HBsAg) because stopping tenofovir in HBV-positive patients can cause hepatitis flares and hepatic decompensation 1, 2, 6
Monitoring Protocol for TAF-Based PrEP in Renal Impairment
Recheck HIV antibody/antigen testing at 1 month after initiation, then every 3 months thereafter 6
Monitor creatinine clearance every 3 months (not every 6 months) due to the patient's baseline renal impairment—this is enhanced monitoring for high-risk patients 1, 2, 6
Screen for sexually transmitted infections (gonorrhea, chlamydia, syphilis) every 3 months 1, 6
Monitor for signs of proximal tubular dysfunction including euglycemic glycosuria, hypophosphatemia, or worsening proteinuria, though this is less likely with TAF than TDF 1, 5
Common Pitfalls to Avoid
Do not attempt to use TDF/FTC with extended dosing intervals (every 48-72 hours) for PrEP in renal impairment—while this approach exists for HIV treatment, it has not been studied or validated for PrEP efficacy and creates high variability in drug exposure 5, 7
Do not delay PrEP initiation while waiting for creatinine results if HIV testing is negative—only HIV testing should gate initiation, though you should have creatinine results before choosing between TAF and TDF formulations 6
Do not use TDF/lamivudine, TAF/emtricitabine alone, or TDF alone—only TDF/emtricitabine or TAF/emtricitabine are approved for PrEP 1
Do not use pericoital "2-1-1" dosing in patients with renal impairment—this regimen is only validated for MSM with normal renal function and infrequent exposures 1
Hepatitis B Considerations
If the patient tests positive for HBsAg, you must use a tenofovir-containing regimen (preferably TAF/FTC given the renal impairment) because discontinuing tenofovir in HBV-positive patients risks hepatitis flares 1, 2
Monitor hepatic function closely for at least several months if PrEP is ever discontinued in an HBV-coinfected patient 4