Objective: To examine the effect of selenium supplementation on CD4(+) T-cell counts, viral suppression, and time to antiretroviral therapy (ART) initiation in ART-naive HIV-infected patients in Rwanda. Methods: A multicenter, double-blinded, placebo-controlled, randomized clinical trial was conducted. Eligible patients were HIV-infected adults (>= 21 years) who had a CD4(+) cell count between 400 and 650 cells/mu l (ART eligibility was >= 350 cells/mu l throughout the trial), and were willing to practice barrier methods of birth control. Patients were randomized to receive once-daily 200mg selenium tablets or identical placebo. They were followed for 24 months with assessments every 6 months. Declines in CD4(+) cell counts were modeled using linear regressions with generalized estimating equations and effect modification, and the composite outcome (ART eligible or ART initiation) using Cox proportional-hazards regression, both conducted with intention to treat. Results: Of the 300 participants, 149 received selenium, 202 (67%) were women, and median age was 33.5 years. The rate of CD4(+) depletion was reduced by 43.8% [95% confidence interval (CI) 7.8-79.8% decrease] in the treatment arm - from mean 3.97 cells/ml per month to mean 2.23 cells/mu l per month. We observed 96 composite outcome events - 45 (47%) in the treatment arm. We found no treatment effect for the composite outcome (hazard ratio 1.00, 95% CI 0.66-1.54) or viral suppression (odds ratio 1.18,95% CI 0.71-1.94). The trial was under powered for the composite outcome due to a lower-than-anticipated event rate. Adverse events were comparable throughout. Conclusions: This randomized clinical trial demonstrated that 24-month selenium supplementation significantly reduces the rate of CD4(+) cell count decline among ART-naive patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.