Effect of cotrimoxazole on mortality in HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis

objective: to determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (art) for human immunodeficiency virus (hiv) infection in low- and middle-income countries through a systematic review and meta-analysis. methods: pubmed and embase were searched for randomized controlled trials and prospective and retrospective cohort studies that compared mortality or morbidity in hiv-infected individuals aged > 13 years on cotrimoxazole and art and on art alone. the newcastle- ottawa quality assessment scale was used to assess selection, confounding and measurement bias. publication bias was assessed using egger's and begg's tests. sensitivity analysis was performed because the i-squared statistic indicated substantial heterogeneity in study results. a random-effects model was used for meta-analysis. findings: nine studies were included. begg and egger p-values for the seven that reported the effect of cotrimoxazole on mortality were 0.29 and 0.49, respectively, suggesting no publication bias. the i-squared statistic was 93.2%, indicating high heterogeneity in study results. the sensitivity analysis showed that neither the follow-up duration nor the percentage of individuals with world health organization stage 3 or 4 hiv disease at baseline explained the heterogeneity. the summary estimate of the effect of cotrimoxazole on the incidence rate of death was 0.42 (95% confidence interval: 0.29-0.61). since most studies followed participants for less than 1 year, it was not possible to determine whether cotrimoxazole can be stopped safely after art-induced immune reconstitution. conclusion: cotrimoxazole significantly increased survival in hiv-infected adults on art. further research is needed to determine the optimum duration of cotrimoxazole treatment in these patients.