Efficacy and safety of the regimens containing tenofovir alafenamide versus tenofovir disoproxil fumarate in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection: A meta-analysis of randomized controlled trials.

Background: Tenofovir disoproxil fumarate (TDF) can cause renal and bone toxicity, which is associated with high plasma tenofovir concentrations in antiretroviral treatment of HIV-1 infected patients. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. We aimed to assess the non-inferiority of a TAF-containing combination regimen versus a TDF-containing fixed-dose single-tablet regimen in the antiretroviral-treatment-naive, HIV-1-infected patients.

Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Trial Registry, from January 2001 to July 2019, using relevant keywords. Available data were extracted from eligible randomized trials (RCTs) and pooled as risk ratios (RRs) or standardized mean differences (SMDs) in a meta-analysis model using Stata/SE.

Results: We included seven eligible randomized controlled trials (RCTs) with a total of 6269 participants. Patients who were antiretroviral-naive adults with HIV-1 on both the TAF-containing regimens and the TDF-containing regimens had similar virologic suppression effects (RR, 1.02; 95% CI, 1.00-1.04; p > 0.05) at week 24 (93.99% vs. 94.20%), week 48 (90.71% vs. 89.54%), and week 96 (86.16% vs. 84.80%). Both groups had no significant improvements in CD4 cell count for the naive patients during 48 weeks of therapy (SMD, 0.09; 95% CI, 0.01 to 0.16; p < 0.05). Both treatments were safe and well-tolerated, and most adverse events were similar as mild to moderate in severity. Moreover, compared with the TDF-containing regimens, the TAF-containing regimens in patients had significantly smaller reductions in both hip (RR, 0.33; 95CI, 0.29-0.39; p < 0.05) and spine (RR, 0.58; 95CI, 0.51-0.65; p < 0.05). Additionally, the TAF-containing regimens in patients had significantly fewer increases for renal events than those of the TDF-containing regimens through 48 weeks (0.31; 95% CI, 0.18-0.55; p < 0.05).

Conclusions: Our meta-analysis indicated that efficacy, safety, and tolerability of TAF-containing regimens were non-inferior in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection. Furthermore, compared with those receiving the TDF-containing regimens, patients on the TAF-containing regimens had significant advantages in renal function, bone parameters, and lipid profile for the naive patients.