ObjectiveTo systematically evaluate the efficacy and safety of early initiation of antiretroviral therapy (ART) in asymptomatic HIV-infected, treatment-naive adults and adolescents. To assess the evidence for the optimal time to initiate ART. MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 4, 2016), CBM, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) about early initiation and optimal time to initiate ART in asymptomatic, treatment-naive HIV-infected patients from January 1996 to April 2016. Two review authors independently assessed study eligibility, extracted data and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. We meta-analysed dichotomous outcomes using the risk ratio (RR) and report the 95% confidence intervals (95% CIs) by using RevMan 5.3 software. ResultsA total of 4 RCTs involving 8 751 patients were included. The results of meta-analysis showed that initiating ART at CD4+ T-cell counts (CD4 counts) ≥350 cells/μL or 500 cells/μL, comparing to deferring initiation of ART to CD4 counts <350 cells/μL, would benefit patients more: (1) Risk of AIDS-defining illnesses which representing disease progression, reduced significantly when starting ART at higher CD4 counts (no less than 350 cells/μL) (RR=0.49, 95%CI 0.38 to 0.64, P<0.001). The reduction of risk was even more significant when initiating ART at CD4 counts of not less than 500 cells/μL (RR=0.38, 95%CI 0.24 to 0.59, P<0.001). (2) When initiating ART at CD4 counts of not less than 350 cells/μL, the risk of serious non-AIDS related events was significantly reduced by 42% (RR=0.58, 95%CI 0.40 to 0.83, P=0.003). When initiating ART at CD4 counts of not less than 500 cells/μL, according to START 2015, the risk of serious non-AIDS related events could be reduced by 39% (RR=0.61, P=0.04). (3) However, when initiating ART at CD4 counts of not less than 350 cells/μL or 500 cells/μL, comparing to deferring initiation, there were no statistically significant differences in death (RR=0.70, 95%CI 0.48 to 1.02, P=0.06) and serious adverse events (RR=0.67, 95%CI 0.38 to 1.20, P=0.18). ConclusionOur findings contribute to the evidence base for recommending initiating ART at CD4 counts of 350-500 cells/μL compared to initiating it later when CD4 counts fall below 350 cells/μL. As for patients with CD4 counts of not less than 500 cells/μL, initiation of ART is also recommended.