Evaluation of tenofovir alafenamide– versus tenofovir disoproxil fumarate–containing regimens on renal outcomes: systematic literature review and meta-analysis

Tenofovir, used for HIV-1 pre-exposure prophylaxis, HIV-1 treatment, and hepatitis B virus (HBV) treatment, is available as the prodrugs tenofovir disoproxil fumarate and tenofovir alafenamide. Tenofovir alafenamide has demonstrated improved renal safety and noninferior efficacy versus tenofovir disoproxil fumarate. This study synthesized evidence on tenofovir disoproxil fumarate and tenofovir alafenamide renal outcomes when used for pre-exposure prophylaxis and treating HIV-1, HBV, and HIV-1/HBV coinfection. A systematic search for studies of pre-exposure prophylaxis and treatment of HIV-1, HBV, and HIV-1/HBV coinfection was conducted in PubMed, EMBASE, Web of Science, and Cochrane Trial Registry from 2017 to 2025 for randomized controlled trials and from 2015 to 2025 for observational cohort studies. Additional randomized controlled trials were identified from a published systematic review. Renal outcomes included changes in estimated glomerular filtration rate, serum creatinine, and biomarkers for proteinuria. A random-effects model was used for meta-analysis. Heterogeneity was assessed using the I2 test. Forty articles (35 randomized controlled trials, 5 observational cohort studies) involving 40,736 participants were included. Pooled estimates of 34 articles showed a statistically significant increase in estimated glomerular filtration rate change with tenofovir alafenamide (2.23 mL/min, 95% confidence interval [CI] 0.98 to 3.48; I2 94.06%) versus tenofovir disoproxil fumarate. Tenofovir alafenamide was associated with a slightly smaller increase in serum creatinine change (–0.02 mg/dL, 95% CI −0.03 to −0.01; I2 92.2%) versus tenofovir disoproxil fumarate across 24 articles. Tenofovir alafenamide was associated with significantly fewer occurrences of proteinuria and albuminuria compared with tenofovir disoproxil fumarate, with the differences becoming increasingly pronounced over time. Tenofovir alafenamide–containing regimens were associated with improved renal safety outcomes over tenofovir disoproxil fumarate–containing regimens across indications. Clinical benefits were more pronounced with longer follow-up durations.