Association of CD4 T cell count and optimal timing of antiretroviral therapy initiation with immune reconstitution inflammatory syndrome and all-cause mortality for HIV-infected adults with newly diagnosed pulmonary tuberculosis: a systematic review and meta-analysis.

aimsCD4 T cell count and optimal timing of antiretroviral therapy (ART) during tuberculosis (TB) treatment are challenging. We conducted a meta-analysis to assess the association of CD4 T cell count and timing of ART initiation with immune reconstitution inflammatory syndrome (IRIS) and all-cause mortality of patients co-infected with HIV/TB.

methodsWe conducted an electronic search of clinical studies dated from January 1980 to December 2019 in PubMed and EMBASE. Randomized, controlled trials evaluating low-base CD4 T cell count (< 50 cells/μL) versus high-base CD4 T cell count (≥ 50 cells/μL), and/or early ART initiation (1 to 28 days after starting TB treatment) versus delayed ART initiation (≥ 28 days after starting TB treatment) were included. The primary endpoints were all-cause mortality and TB-related immune reconstitution inflammatory syndrome (IRIS-TB). The risk ratio (RR) was calculated as a measure of intervention effect. Mantel-Haenszel method was used to estimate the RR.

resultsTen trials (n = 5226) were conducted in North America, Africa, and Asia. We found that low-baseline CD4 T cell count increased the incidence of TB-associated IRIS (RR, 1.47; 95% CI, 1.24-1.75; I

conclusionsThe present study demonstrates that low-baseline CD4 T cell count (< 50 cells/μL) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS and all-cause mortality. Early ART initiation (≤ 28 days) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS. However, evidence is insufficient to refute or support a survival benefit conferred by the comparison between early ART initiation (≤ 28 days) and delayed ART initiation.