Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

Abstract

BACKGROUND:

Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV.

METHODS:

Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment.

FINDINGS:

We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL.

INTERPRETATION:

In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

• Authors: N Sarita Shah, Cissy Kityo, Michael D Hughes, Caitlyn McCarthy, Carole Wallis, Mina Hosseinipour, Deborah Langat, Mulinda Nyirenda, Mohammed Rassool, Rodney Dawson, Yvetot Joseph, Fatma Some, Rosie Mngqbisa, Pamela Grace Mukwekwerere, Elizabeth Woolley, Catherine Godfrey, Yukari C Manabe, John W Mellors, Charles Flexner, Gary Maartens, ACTG A5381/Hakim Study Team
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) (May 13 2024) ISSN: 1537-6591 [Electronic] United States
• PMID: 38739755 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].