Abstract
The reconstitution of Mycobacterium tuberculosis antigen-specific CD4 T cells in a cohort of HIV-infected persons starting antiretroviral treatment (ART) in a high tuberculosis endemic area is described. Restoration of the antigen-specific CD4 T-cell subsets mirrored the overall CD4 T-cell compartment. Activation (assessed by HLA-DR expression) decreased during ART but remained elevated compared to HIV-uninfected persons. Despite known M. tuberculosis sensitization determined by interferon-γ release assay, 12/23 participants had no M. tuberculosis-specific CD4 T cells detectable by flow cytometry, combined with overall elevated T-cell activation and memory differentiation, suggesting heightened turnover. Our data suggest early ART initiation to maintain polyfunctional immune memory responses.
Highlights
Human immunodeficiency virus (HIV-1) infection is the biggest risk factor for development of tuberculosis
To better understand the dynamics of M. tuberculosis antigenspecific CD4+ T-cell reconstitution during the first 6 month of antiretroviral treatment (ART), we first defined the dynamics of replenishment of the whole CD4 T-cell compartment
The study cohort originated from Khayelitsha township, a highly tuberculosis endemic area, with the prevalence of M. tuberculosis infection reported to be approximately 69% [8]
Summary
Human immunodeficiency virus (HIV-1) infection is the biggest risk factor for development of tuberculosis. Antiretroviral therapy (ART) reduces the risk of tuberculosis in HIV-1–coinfected persons. This therapy is associated with tuberculosis decline in sub-Saharan Africa between 2003 and 2016, with an estimated 1.88 million tuberculosis cases prevented [1]. The incidence of tuberculosis remains higher in HIV-1–infected persons despite ART (compared to those HIV-1 uninfected), regardless of the duration of ART or CD4 count [2]. This could be due to depletion of Mycobacterium tuberculosis-specific T cells early during HIV-1 infection [3], as well as impairment of function of these antigen-specific CD4 T cells [4]. We compare the reconstitution of the whole CD4 T-cell compartment to that of the M. tuberculosis antigen-specific CD4 T-cell compartment, during the first 6 months of ART using flow cytometry, in a cohort of M. tuberculosis-sensitized HIV-infected persons starting ART, in an area with high prevalence of latent tuberculosis infection [8]
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