The Impact of HIV Viral Suppression and Immune Status on Rifampicin-Resistant Tuberculosis Outcomes: A Systematic...

Background/Objectives: Rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection remain major contributors to morbidity and mortality, particularly in high-burden settings. HIV-related clinical factors, including viral suppression, CD4-defined immune status, HIV drug resistance, virological failure, and ART failure, may influence RR-TB treatment response; however, existing evidence remains fragmented. This systematic review and meta-analysis protocol aims to synthesize evidence on the impact of HIV viral suppression, immune status, and HIV drug resistance/ART resistance status on RR-TB treatment outcomes. Methods: This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Published peer-reviewed studies and relevant grey literature from January 2005 to December 2025 will be searched in PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, ScienceDirect, EBSCOhost, PsycINFO, Google Scholar, and other relevant sources. No language restriction will be applied at the search stage. Where feasible, non-English records will be translated for title/abstract and full-text screening. Two reviewers will independently screen studies, extract data, and assess study quality, with disagreements resolved by a third reviewer. Study-level risk of bias will be assessed using design-appropriate tools, and the certainty of evidence for each outcome will be evaluated using GRADE. Results: Evidence will be synthesized narratively and, where studies are sufficiently homogeneous, quantitatively through meta-analysis. Outcomes of interest will include treatment success, treatment failure, mortality, treatment completion, microbiological cure, and adverse events. Subgroup analyses will be considered by viral suppression status, CD4-defined immune status, HIV drug resistance/ART resistance status, geographic region, and treatment regimen where data permit. Conclusions: This review will provide evidence on how HIV viral suppression, immune status, and HIV drug resistance/ART resistance influence RR-TB treatment outcomes. The findings may inform integrated TB/HIV care, clinical monitoring, and treatment strategies for individuals co-infected with HIV and RR-TB.