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

Aims CD4 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. Methods We 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 ( Results Ten 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 2 = 58%) and all-cause mortality (RR, 2.42; 95% CI, 1.71-3.42; I 2 = 41%) compared with high baseline CD4 T cell count, and early ART initiation increased the incidence of TB-associated IRIS compared with delayed ART initiation (RR, 1.80; 95% CI, 1.57-2.07; I 2 = 74%). However, early ART initiation did not reduce all-cause mortality (RR, 0.91; 95% CI, 0.74-1.12; I 2 = 49%) compared with delayed ART initiation. Conclusions The 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.