Open AccessIsoniazid and Rifapentine Treatment Eradicates Persistent Mycobacterium tuberculosis in Macaques
Author(s) -
Taylor W. Foreman,
Allison N. Bucşan,
Smriti Mehra,
Charles A. Peloquin,
Lara A. Doyle,
Kasi RussellLodrigue,
Neel R Gandhi,
John D. Altman,
Cheryl L. Day,
Joel D. Ernst,
Henry M. Blumberg,
Jyothi Rengarajan,
Deepak Kaushal
Publication year - 2020
Publication title -
american journal of respiratory and critical care medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.272
H-Index - 374
eISSN - 1535-4970
pISSN - 1073-449X
DOI - 10.1164/rccm.201903-0646oc
Subject(s) - rifapentine , medicine , isoniazid , tuberculosis , mycobacterium tuberculosis , virology , microbiology and biotechnology , latent tuberculosis , pathology , biology
Rationale: Direct evidence for persistence of Mycobacterium tuberculosis ( Mtb ) during asymptomatic latent tuberculosis infection (LTBI) in humans is currently lacking. Moreover, although a 12-week regimen of once-weekly isoniazid and rifapentine (3HP) is currently recommended by the CDC as treatment for LTBI, experimental evidence for 3HP-mediated clearance of persistent Mtb infection in human lungs has not been established. Objectives: Using a nonhuman primate (NHP) model of TB, we sought to assess 3HP treatment-mediated clearance of Mtb infection in latently infected macaques. Methods: Sixteen NHPs were infected via inhalation with ∼10 cfu of Mtb CDC1551, after which asymptomatic animals were either treated with 3HP or left untreated. Pharmacokinetics of the 3HP regimen were measured. Following treatment, animals were coinfected with simian immunodeficiency virus to assess reactivation of LTBI and development of active TB disease. Measurements and Main Results: Fourteen NHPs remained free of clinical signs or microbiological evidence of active TB following infection with Mtb and were subsequently either treated with 3HP ( n = 7) or left untreated ( n = 7). Untreated NHPs were asymptomatic for 7 months but harbored persistent Mtb infection, as shown by reactivation of latent infection following simian immunodeficiency virus coinfection. However, none of the treated animals developed TB reactivation disease, and they remained without clinical or microbiological evidence of persistent bacilli, suggesting treatment-mediated clearance of bacteria. Conclusions: Mtb can persist in asymptomatic macaques for at least 7 months. Furthermore, 3HP treatment effectively cleared bacteria and prevented reactivation of TB in latently infected macaques.