Background: Pyrimethamine and sulfadiazine (P-S) combination is effective and considered the mainstay therapy for cerebral toxoplasmosis (CT). Alternative treatment regimens are available, but their relative efficacy and tolerability are not well known. Particularly, trimephoprim-sulfamethaxozole (TMP-SMX) shows potential advantages (i.e., tolerability, posology, parenteral formulation, cost, and accessibility) but its use is infrequent when P-S is available. Methods: We searched PubMed and 4 other databases to identify randomized controlled trials (RCTs) and cohort studies comparing different regimens for the treatment of HIV-associated CT. Two independent reviewers searched and identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. Results: Nine studies were included (5 RCTs, 3 retrospective cohorts, 1 prospective cohort). Treatment with P-S has the same or better clinical efficacy than P-C or TMP-SMX in terms of partial or complete response clinical response (P-C vs P-S: RR 0.87, 95%CI 0.70-1.08; TMP-SMX vs P-S: RR 0.97, 95%CI 0.78-1.21) and radiological response (P-C vs P-S: RR 0.92, 95%CI 0.82-1.03). Safety profile in terms of skin rash (P-C vs P-S: RR 0.81, 95%CI 0.56-1.17; TMP-SMX vs P-S: RR 0.17, 95%CI 0.02-1.29), liver impairment (P-C vs P-S: RR 0.48, 95%CI 0.24-0.97) and drug discontinuation due to adverse events (P-C vs P-S: RR 0.32, 95%CI 0.07-1.47) were worse with P-S regimen. Conclusion: The available evidence fails to identify any one superior regimen for the treatment of CT. However, P-S regimen has worse safety profile than P-C or TMP-SMX. Although current evidence does not allow a definitive recommendation, use of TMP-SMX for treatment of HIV-associated CT is consistent with the available data. More large studies comparing alternative therapies are needed. / IDWeek, Evento que se llevó a cabo del 7 -11 de Octubre de 2015, en la ciudad de San Diego, CA, EE.UU. Evento Sesión HIV: Other Opportunistic Infections in HIV. Saturday, October 10, 2015. Room: Poster Hall