Background: Nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) with boosted protease inhibitors are included in standardized first-line and second-line regimens. Recent World Health Organization (WHO) guidelines recommend a boosted protease inhibitor (PI) combined with 2 NRTIs or raltegravir as a second-line regimen.Objective: Ritonavir-boosted lopinavir (LPV/r) is known as a key second-line antiretroviral therapy (ART) in resource-limited settings. We carried out a meta-analysis to analyze virologic suppression and effectiveness of LPV/r-based second-line therapy in HIV-infected patients.Methods: In this meta-analysis, we searched randomized controlled trials and observational cohort studies to evaluate outcomes of second-line ART for patients with HIV who failed first-line therapy. A systematic search was conducted in Pubmed, Cochrane Library, and Embase from inception to January 2018. Outcomes included viral suppression, CD4 cell counts, drug resistance, adverse events, and self-reported adherence. We assessed comparative efficacy and safety in a meta-analysis. Data analysis was performed using RevMan 5.3 and Stata12.0.Results: Nine studies comprising 3,923 patients were included in the meta-analysis. The overall successful virologic suppression rate of the second-line regimen was 77% (ITT) and 87% (PP) at 48 weeks with a plasma HIV RNA load of