Systematic review of therapeutic outcomes of multidrug resistant tuberculosis and their predictors in adults receiving integrated treatment of tuberculosis and human immuno-deficiency virus in low- and middle-income countries: a study protocol.

Background: Programs that integrate tuberculosis (TB) and human immunodeficiency virus (HIV) treatment aim to provide efficient treatment services and maximize successful treatment outcomes through the delivery of both TB and HIV treatment by one provider at the same time and location. However, multi-drug resistant tuberculosis (MDR-TB) is more difficult to treat as compared to drug-sensitive TB, and in low- and middle-income countries (LMICs), the potential of programs integrating TB/HIV treatment to sustain favourable MDR-TB treatment outcomes is poorly elucidated. The objective of this review is to perform a systematic collection, critical appraisal and synthesis of existing evidence on therapeutic outcomes of MDR-TB and their predictors among adults receiving integrated treatment for TB/HIV in LMICs.

Methods: A systematic review of quantitative evidence from observational cohort studies will be performed. MEDLINE, Embase, and Global Health electronic databases will be searched for relevant studies published from March 2004 to December 2019. Two investigators will independently screen the search output, review the eligible studies, and assess the quality of the eligible studies using quality assessment tools of the National Heart Lung and Blood Institute. Random-effects meta-analysis will be used to obtain summary estimates. Heterogeneity across studies will be assessed using the I statistic. The confidence in the summary estimates will be rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The final review will be reported following the guidelines of the Preferred Reporting System for Systematic Reviews and Meta-analysis, presented at scientific conferences and published in a peer-reviewed journal.

Discussion: This study is expected to report the performance of integrated TB/HIV treatment programs as regards their potential to uphold successful MDR-TB treatment outcomes in LMICs. Furthermore, the review will indicate patient-related and healthcare-related factors that should be addressed to improve on survival of patients with MDR-TB/HIV co-infection in LMICs.

Systematic Review Registration: This review has been registered with the International Prospective Register of Systematic Reviews and the reference ID is CRD42020159745.