OBJECTIVES: No cure for HIV currently exists, however antiretroviral (ARV) drugs can control disease progression. The objective of this study was to carry out a mixed-treatment comparison (MTC) of randomized controlled trials (RCTs) to assess the relative efficacy and safety of ARV drugs used in treatment-experienced (TE) patients. MTCs synthesise available evidence by combining direct and indirect comparisons. METHODS: All phase II and III RCTs published in the past five years, assessing the efficacy of etravirine (ETR), maraviroc (MVC) and raltegravir (RAL) in combination with optimized background therapy (OBT) compared to OBT alone in TE HIV patients were identified. Data on patient characteristics, CD4 cell count changes, virological suppression (percentage of HIV RNA <50 copies/mL and <400 copies), common adverse events (diarrhoea, nausea), discontinuations and deaths were extracted. A Bayesian fixed-effect mixed-treatment network analysis was performed on efficacy and safety outcomes at 48 and 96 weeks. RESULTS: Twenty-two studies were identified; six were included in the MTC network based on data availability (i.e. BENCHMRK 1 and 2, DUET 1 and 2 and MOTIVATE 1 and 2). All treatments showed increased efficacy compared to OBT. MVC twice daily was associated with an increased virological suppression (mean odds ratio = 1.66 for <400 copies and 1.88 for < 50 copies) and larger CD4 count increase (mean change of 40 cells/mL) compared to ETR at 48 weeks. MVC’s superior efficacy to ETR was maintained at week 96. MVC was no different to RAL at week 48 but superior to RAL at 96 weeks for both efficacy outcomes. For safety outcomes, no differences between treatments were found. CONCLUSIONS: In the absence of head-to-head trials comparing active drugs, this study provides information on the relative efficacy of each regimen. It confirms the significant clinical value of MVC compared to ETR and RAL in treatment-experienced patients.