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

Abstract

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 (<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. 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; I2 = 58%) and all-cause mortality (RR,
2.42; 95% CI, 1.71–3.42; I2 = 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; I2 = 74%).
However, early ART initiation did not reduce all-cause mortality (RR, 0.91; 95% CI, 0.74–1.12; I2 = 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.

Authors

Li L, Li J, Chai C, Liu T, Li P, Qu M, Zhao H

Year

2021

Topics

  • Population(s)
    • General HIV+ population
  • Prevention, Engagement and Care Cascade
    • Engagement and Care Cascade
  • Engagement and Care Cascade
    • Treatment
  • Co-infections
    • Tuberculosis

Link

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