Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project

Abstract

Background: HIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings.

Setting: Demonstration project in 2 sexually transmitted infection clinics and a community health center.

Methods: We evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI).

Results: From October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR <70 mL/min/1.73 m; independent predictors of this outcome were age ≥40 years (OR 3.79, 95% CI: 1.43 to 10.03) and baseline eGFR <90 mL/min/1.73 m (OR 9.59, 3.69-24.94).

Conclusions: In a demonstration setting, daily tenofovir-disoproxil-fumarate/emtricitabine PrEP leads to reduced CrCl and eGFR; however, these eGFR changes are based on very small changes in serum creatinine and seem to be nonprogressive after the first 12 weeks. Future studies are needed to understand the prognostic significance of these small changes.

Figure 1

Mean change in creatinine clearance (top panel) and serum creatinine (bottom panel) from baseline to 48 weeks in a demonstration project of HIV preexposure prophylaxis among men who have sex with men using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). Number of participants with available data at each study visit is represented by n. Bars represent standard errors. Results were similar when including only participants who returned for all four quarterly follow-up visits.

Figure 2

Mean change in creatinine clearance (top panel) and serum creatinine (bottom panel) from baseline to week 12 by tenofovir disoproxil level (TFV-DP) in dried blood spots among men who have sex with men in a demonstration project of HIV preexposure prophylaxis using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). Number of participants in each category is represented by n. Bars represent standard errors.

Figure 3

Urine protein level from results of urine dipstick by study week among men who have sex with men in a demonstration project of preexposure prophylaxis using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). Number of participants in each category is represented by n. Results were similar when including only participants who returned for all four quarterly follow-up visits.