The effect of peer support on virologic and immunologic treatment outcomes among HIVinfected patients receiving antiretroviral therapy (ART) was assessed in a cluster randomized controlled trial in Vietnam. Seventy-one clusters (communes) were randomized in intervention or control, and a total of 640 patients initiating ART were enrolled. The intervention group received peer support with weekly home-visits. Both groups received first-line ART regimens according to the National Treatment Guidelines. Viral load (VL) (ExaVir™ Load) and CD4 counts were analyzed every 6 months. The primary endpoint was virologic failure (VL >1000 copies/ml). Patients were followed up for 24 months. Intention-to-treat analysis was used. Cluster longitudinal and survival analyses were used to study time to virologic failure and CD4 trends. Of 640 patients, 71% were males, mean age 32 years, 83% started with stavudine/lamivudine/nevirapine regimen. After a mean of 20.8 months, 78% completed the study, and the median CD4 increase was 286 cells/μl. Cumulative virologic failure risk was 7.2%. There was no significant difference between intervention and control groups in risk for and time to virologic failure and in CD4 trends. Risk factors for virologic failure were ART-non-naïve status aHR 6.9;(95% CI 3.2-14.6); p < 0.01; baseline VL ≥100,000 copies/ml aHR 2.3;(95% CI 1.2-4.3); p < 0.05 and incomplete adherence (self-reported missing more than one dose during 24 months) aHR 3.1;(95% CI 1.1-8.9); p < 0.05. Risk factors associated with slower increase of CD4 counts were: baseline VL ≥100,000 copies/ml adj.sq.Coeff (95% CI): -0.9 (-1.5;-0.3); p < 0.01 and baseline CD4 count <100 cells/μl adj.sq.Coeff (95% CI): -5.7 (-6.3;-5.4); p < 0.01. Having an HIV-infected family member was also significantly associated with gain in CD4 counts adj.sq.Coeff (95% CI): 1.3 (0.8;1.9); p < 0.01. There was a low virologic failure risk during the first 2 years of ART follow-up in a rural low-income setting in Vietnam. Peer support did not show any impact on virologic and immunologic outcomes after 2 years of follow up. NCT01433601 .