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

J Clin Invest. 2020 Oct 1;130(10):5171-5179. doi: 10.1172/JCI136502.


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.

Keywords: AIDS/HIV; Infectious disease; Tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-HIV Agents / therapeutic use
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Bacterial Load
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Coinfection / drug therapy*
  • Disease Models, Animal
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Humans
  • Latent Tuberculosis / complications*
  • Latent Tuberculosis / microbiology
  • Latent Tuberculosis / pathology
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome / complications*
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus
  • Viral Load / drug effects


  • Anti-HIV Agents
  • Anti-Retroviral Agents