Dolutegravir-based Antiretroviral Therapy for Patients Coinfected with Tuberculosis and Human Immunodeficiency Virus: A Multicenter, Noncomparative, Open-label, Randomized Trial

Kelly E. Dooley, Richard Kaplan, Noluthando Mwelase, Beatriz Grinsztejn, Eduardo Ticona, Marcus Lacerda, Omar Sued, Elena Belonosova, Mounir Ait-Khaled, Konstantinos Angelis, Dannae Brown, Rajendra Singh, Christine L. Talarico, Allan R. Tenorio, Michael R. Keegan, Michael Aboud, Kelly E. Dooley, Kaplan Richard, Mwelase Noluthando, Grinsztejn BeatrizTicona Chavez Eduardo, Lacerda Marcus, Sued Omar, Belonosova Elena, Ait Khaled Mounir, Angelis Konstantinos, Brown Dannae, Singh Rajendra, Christine L. Talarico, Allan R. Tenorio, Michael R. Keegan, Aboud Michael, Lupo Sergio, Cahn Pedro, Porteiro Norma, Daniel Lopardo Gustavo, Riegel Santos Breno, Madruga Jose, Roberto Alves Carlos, Patricia Quintero Perez Nora, Rodriguez Noriega Eduardo, Perez Rios Alma, Perez Patrigeon Santiago, Mosqueda Gómez Juan-Luis, Paredes Paredes Mercedes, Rodriguez Aldo, Mac Rae John, Casapia Wilfredo, Sanchez Vergaray Eduardo, Belonosova Elena, Sultanov Lenar, Ivanova Elvira, Yakovlev Alexey, Panteleev Alexander, Dawson Rodney, Latiff Gulam, Mohapi Lerato, Taljaard Jantjie, Jurgens Lombaard Johannes, Khan Mohammed, Variava Ebrahim, Chetchotisakd Ploenchan, Kiertiburanakul Sasisopin, Avihingsanon Anchalee

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Abstract

© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. Background: The concurrent treatment of tuberculosis and human immunodeficiency virus (HIV) is challenging, owing to drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir (DTG) were assessed in adults with HIV and drug-susceptible tuberculosis. Methods: International Study of Patients with HIV on Rifampicin ING is a noncomparative, active-control, randomized, open-label study in HIV-1-infected antiretroviral therapy-naive adults (CD4+ ≥50 cells/mm3). Participants on rifampicin-based tuberculosis treatment ≤8 weeks were randomized (3:2) to receive DTG (50 mg twice daily both during and 2 weeks after tuberculosis therapy, then 50 mg once daily) or efavirenz (EFV; 600 mg daily) with 2 nucleoside reverse transcriptase inhibitors for 52 weeks. The primary endpoint was the proportion of DTG-arm participants with plasma HIV-1-RNA <50 copies/mL (responders) by the Food and Drug Administration Snapshot algorithm (intent-to-treat exposed population) at Week 48. The study was not powered to compare arms. Results: For DTG (n = 69), the baseline HIV-1 RNA was >100 000 copies/mL in 64% of participants, with a median CD4+ count of 208 cells/mm3; for EFV (n = 44), 55% of participants had HIV-1 RNA >100 000 copies/mL, with a median CD4+ count of 202 cells/mm3. The Week 48 response rates were 75% (52/69, 95% confidence interval [CI] 65-86%) for DTG and 82% (36/44, 95% CI 70-93%) for EFV. The DTG nonresponses were driven by non-treatment related discontinuations (n = 10 lost to follow-up). There were no deaths or study drug switches. There were 2 discontinuations for toxicity (EFV). There were 3 protocol-defined virological failures (2 DTG, no acquired resistance; 1 EFV, emergent resistance to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors). The tuberculosis treatment success rate was high. Tuberculosis-associated IRIS was uncommon (4/arm), with no discontinuations for IRIS. Conclusions: Among adults with HIV receiving rifampicin-based tuberculosis treatment, twice-daily DTG was effective and well tolerated. Clinical Trials Registration: NCT02178592.
Original languageAmerican English
Pages (from-to)549-556
Number of pages8
JournalClinical Infectious Diseases
DOIs
StatePublished - 3 Feb 2020

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