Dolutegravir-based Antiretroviral Therapy for Patients Coinfected With Tuberculosis and Human Immunodeficiency Virus: A Multicenter, Noncomparative, Open-label, Randomized Trial
Authors: Dooley Kelly E , Kaplan Richard , Mwelase Noluthando , Grinsztejn Beatriz , Ticona Eduardo , Lacerda Marcus , Sued Omar , Belonosova Elena , Ait-Khaled Mounir , Angelis Konstantinos , Brown Dannae , Singh Rajendra , Talarico Christine L , Tenorio Allan R , Keegan Michael R , Aboud Michael ,   International Study of Patients with HIV on Rifampicin ING study group, Dooley Kelly E , Richard Kaplan , Noluthando Mwelase , Beatriz Grinsztejn , Eduardo Ticona Chavez , Marcus Lacerda , Omar Sued , Elena Belonosova , Mounir Ait-Khaled , Konstantinos Angelis , Dannae Brown , Rajendra Singh , Talarico Christine L , Tenorio Allan R , Keegan Michael R , Michael Aboud , Sergio Lupo , Pedro Cahn , Norma Porteiro , Gustavo Daniel Lopardo , Breno Riegel Santos , Jose Madruga , Carlos Roberto Alves , Nora Patricia Quintero Perez , Eduardo Rodriguez Noriega , Alma Perez Rios , Santiago Perez Patrigeon , Juan-Luis Mosqueda-Gómez , Mercedes Paredes Paredes , Aldo Rodriguez , John Mac Rae , Wilfredo Casapia , Eduardo Sanchez Vergaray , Elena Belonosova , Lenar Sultanov , Elvira Ivanova , Alexey Yakovlev , Alexander Panteleev , Rodney Dawson , Gulam Latiff , Lerato Mohapi , Jantjie Taljaard , Johannes Jurgens Lombaard , Mohammed Khan , Ebrahim Variava , Ploenchan Chetchotisakd , Sasisopin Kiertiburanakul , Anchalee Avihingsanon 
Published: March 2019

Abstract

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 &lt;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 &gt;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 &gt;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.