Antiretroviral treatment does not prevent extrapulmonary tuberculosis during SIV/Mtb coinfection in macaques

Coinfection with both HIV and M. tuberculosis (Mtb) results in disseminated tuberculosis (TB) and accelerated HIV progression. Despite greater access to antiretroviral treatment (ART), it remains unclear whether suppression of HIV replication protects against severe Mtb infection. Here, using a macaque model of SIV/Mtb coinfection, we investigated whether treatment of SIV infection with ART influenced control of a subsequent Mtb challenge compared with SIV-infected macaques that were not treated with ART. Macaques were first infected with SIVB670, SIVB670 with ART, or saline followed by a low-dose Mtb inoculation with serial clinical and PET-CT imaging assessments. At necropsy, gross pathology, viremia, bacterial burden, and immunologic parameters were compared. SIV-TB animals had greater gross pathology and total bacterial burden than TB-only and SIV/ART/TB groups. However, despite normal blood CD4 counts and undetectable SIV RNA, SIV/ART/TB macaques showed similar clinical parameters and extrapulmonary involvement as SIV/TB animals. Analysis of barcoded-Mtb suggests that ART control of SIV replication did not prevent Mtb extrapulmonary dissemination. These data indicate that people living with HIV on ART remain at high risk of bacterial dissemination and extrapulmonary TB disease. Understanding the mechanisms of extrapulmonary spread and disease severity during HIV/TB coinfection remains an important issue.