Antiretroviral therapy does not reduce tuberculosis reactivation in a tuberculosis-HIV coinfection model

Abstract

While the advent of combination antiretroviral therapy (ART) has significantly improved survival, tuberculosis (TB) remains the leading cause of death in the HIV-infected population. We used Mycobacterium tuberculosis/simian immunodeficiency virus-coinfected (M. tuberculosis/SIV-coinfected) macaques to model M. tuberculosis/HIV coinfection and study the impact of ART on TB reactivation due to HIV infection. Although ART significantly reduced viral loads and increased CD4 + T cell counts in blood and bronchoalveolar lavage (BAL) samples, it did not reduce the relative risk of SIV-induced TB reactivation in ART-treated macaques in the early phase of treatment. CD4 + T cells were poorly restored specifically in the lung interstitium, despite their significant restoration in the alveolar compartment of the lung as well as in the periphery. IDO1 induction in myeloid cells in the inducible bronchus-associated lymphoid tissue (iBALT) likely contributed to dysregulated T cell homing and impaired lung immunity. Thus, although ART was indispensable for controlling viral replication, restoring CD4 + T cells, and preventing opportunistic infection, it appeared inadequate in reversing the clinical signs of TB reactivation during the relatively short duration of ART administered in this study. This finding warrants the modeling of concurrent treatment of TB and HIV to potentially reduce the risk of reactivation of TB due to HIV to inform treatment strategies in patients with M. tuberculosis/HIV coinfection.

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

“…Tissue processing, flow cytometry, multiplex cytokine analyses, immunohistochemistry, multicolour confocal microscopy and SARS-CoV-2 specific-antibody response detection for immune evaluations. Flow cytometry was performed as previously described 14,33 on blood and BAL samples collected on days 3, 6, 9 and 12, and at the end point, which occurred at 14-17 d.p.i. for various animals.…”

Impact of Helminth Infections on Female Reproductive Health and Associated Diseases

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“…Combination antiretroviral therapy (cART) has drastically curtailed morbidity and mortality in people living with HIV (PLHIV) (1). Still, PLHIV remain at an increased risk for pneumococcal infections, Mycobacterium tuberculosis (M. tuberculosis) reactivation and impaired vaccine responses (2)(3)(4)(5)(6). Moreover, HIV infection predisposes to non-infectious comorbidities, such as cardiovascular disease and non-AIDSrelated cancer, which share an underlying pathophysiological pathway characterized by a persisting and inappropriate activation of innate and adaptive immune cells (7,8).…”