Comparative effectiveness of tenofovir in treatment-naïve HIV-infected patients: systematic review and meta-analysis
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INTRODUCTION: Benefits and harms of tenofovir disoproxil fumarate (TDF) in HIV-infected, antiretroviral treatment (ART)-naïve patients of any age have not been systematically reviewed since recent milestone trials were published. METHODS: We searched MEDLINE, EMBASE, CENTRAL, SCI, LILACS, WHO GHL, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing TDF-based treatments with any other ART-regimen (last search 01/2015). Trial characteristics and results were extracted, risks of bias systematically assessed, and treatment effects synthesized in meta-analyses using random-effects models. RESULTS: We included 22 RCTs (8297 patients). We found no differences between groups for mortality, AIDS, fractures, CD4 cell count, and virological failure; and inconclusive information due to inadequate reporting for cardiovascular events, renal failure, proteinuria, rash, and quality of life. Tenofovir disoproxil fumarate-based regimens significantly reduced total cholesterol (mean difference -18.42 mg/dl; 95% confidence interval [CI] -22.80 to -14.0), LDL-cholesterol (-9.53 mg/dl; -12.16 to -6.89), HDL-cholesterol (-2.97 mg/dl; -4.41 to -1.53), and triglycerides (-29.77 mg/dl; -38.61 to -20.92), bone mineral density (BMD) (hip: -1.41%; -1.87 to -0.94), and glomerular filtration rate (eGFR) (-3.47 ml/minute; -5.89 to -1.06) over 48 weeks of follow-up. Effects were similar in trials comparing fixed-dose TDF/FTC-based regimens with ABC/3TC-based regimens. We found no influence of baseline viral load on virological failure. DISCUSSION: Moderate-quality evidence suggests similar effects of TDF-based treatment regimens and other ART on virological failure. Tenofovir disoproxil fumarate-based regimens are associated with a more favorable lipid profile, but with increased risk of reduced BMD and eGFR. Improved reporting quality is vital to allow assessment of clinical outcomes in future trials.
