PMID- 30918967 OWN - NLM STAT- MEDLINE DCOM- 20210106 LR - 20210106 IS - 1537-6591 (Electronic) IS - 1058-4838 (Linking) VI - 70 IP - 4 DP - 2020 Feb 3 TI - Dolutegravir-based Antiretroviral Therapy for Patients Coinfected With Tuberculosis and Human Immunodeficiency Virus: A Multicenter, Noncomparative, Open-label, Randomized Trial. PG - 549-556 LID - 10.1093/cid/ciz256 [doi] AB - 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 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. CI - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. FAU - Dooley, Kelly E AU - Dooley KE AD - Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Kaplan, Richard AU - Kaplan R AD - Desmond Tutu Human Immunodeficiency Virus (HIV) Foundation, Cape Town. FAU - Mwelase, Noluthando AU - Mwelase N AD - Clinical HIV Research Unit, Johannesburg, South Africa. FAU - Grinsztejn, Beatriz AU - Grinsztejn B AD - Instituto de Pesquisa Clinica Evandro Chagas Fundacao Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. FAU - Ticona, Eduardo AU - Ticona E AD - Hospital Nacional Dos de Mayo, Universidad Nacional Mayor de San Marcos, Lima, Peru. FAU - Lacerda, Marcus AU - Lacerda M AD - Instituto Leonidas & Maria Deane (Fiocruz)/Tropical Medicine Foundation Dr Heitor Vieira Dourado, Manaus, Brazil. FAU - Sued, Omar AU - Sued O AD - Fundacion Huesped, Buenos Aires, Argentina. FAU - Belonosova, Elena AU - Belonosova E AD - Regional Center For Prevention and Treatment of Acquired Immunodeficiency Syndrome and Infectious Diseases, Orel, Russia. FAU - Ait-Khaled, Mounir AU - Ait-Khaled M AD - ViiV Healthcare Ltd., Brentford. FAU - Angelis, Konstantinos AU - Angelis K AD - GlaxoSmithKline, Uxbridge, United Kingdom. FAU - Brown, Dannae AU - Brown D AD - ViiV Healthcare Ltd., Melbourne, Victoria, Australia. FAU - Singh, Rajendra AU - Singh R AD - GlaxoSmithKline, Collegeville, Pennsylvania. FAU - Talarico, Christine L AU - Talarico CL AD - ViiV Healthcare, Research Triangle Park, North Carolina. FAU - Tenorio, Allan R AU - Tenorio AR AD - ViiV Healthcare, Research Triangle Park, North Carolina. FAU - Keegan, Michael R AU - Keegan MR AD - ViiV Healthcare Ltd., Brentford. FAU - Aboud, Michael AU - Aboud M AD - ViiV Healthcare Ltd., Brentford. CN - International Study of Patients with HIV on Rifampicin ING study group LA - eng SI - ClinicalTrials.gov/NCT02178592 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Infect Dis JT - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JID - 9203213 RN - 0 (Anti-HIV Agents) RN - 0 (Heterocyclic Compounds, 3-Ring) RN - 0 (Oxazines) RN - 0 (Piperazines) RN - 0 (Pyridones) RN - 0 (RNA, Viral) RN - DKO1W9H7M1 (dolutegravir) SB - IM CIN - Clin Infect Dis. 2020 Feb 3;70(4):557-558. PMID: 30906946 MH - Adult MH - *Anti-HIV Agents/therapeutic use MH - CD4 Lymphocyte Count MH - *Coinfection/drug therapy MH - *HIV Infections/complications/drug therapy MH - Heterocyclic Compounds, 3-Ring/adverse effects MH - Humans MH - Oxazines MH - Piperazines MH - Pyridones MH - RNA, Viral MH - Treatment Outcome MH - *Tuberculosis/complications/drug therapy MH - Viral Load OTO - NOTNLM OT - HIV OT - dolutegravir OT - efavirenz OT - immune reconstitution inflammatory syndrome OT - tuberculosis FIR - Dooley, Kelly E IR - Dooley KE FIR - Richard, Kaplan IR - Richard K FIR - Noluthando, Mwelase IR - Noluthando M FIR - Beatriz, Grinsztejn IR - Beatriz G FIR - Eduardo, Ticona Chavez IR - Eduardo TC FIR - Marcus, Lacerda IR - Marcus L FIR - Omar, Sued IR - Omar S FIR - Elena, Belonosova IR - Elena B FIR - Mounir, Ait-Khaled IR - Mounir AK FIR - Konstantinos, Angelis IR - Konstantinos A FIR - Dannae, Brown IR - Dannae B FIR - Rajendra, Singh IR - Rajendra S FIR - Talarico, Christine L IR - Talarico CL FIR - Tenorio, Allan R IR - Tenorio AR FIR - Keegan, Michael R IR - Keegan MR FIR - Michael, Aboud IR - Michael A FIR - Sergio, Lupo IR - Sergio L FIR - Pedro, Cahn IR - Pedro C FIR - Norma, Porteiro IR - Norma P FIR - Gustavo, Daniel Lopardo IR - Gustavo DL FIR - Breno, Riegel Santos IR - Breno RS FIR - Jose, Madruga IR - Jose M FIR - Carlos, Roberto Alves IR - Carlos RA FIR - Nora, Patricia Quintero Perez IR - Nora PQP FIR - Eduardo, Rodriguez Noriega IR - Eduardo RN FIR - Alma, Perez Rios IR - Alma PR FIR - Santiago, Perez Patrigeon IR - Santiago PP FIR - Juan-Luis, Mosqueda-Gomez IR - Juan-Luis MG FIR - Mercedes, Paredes Paredes IR - Mercedes PP FIR - Aldo, Rodriguez IR - Aldo R FIR - John, Mac Rae IR - John MR FIR - Wilfredo, Casapia IR - Wilfredo C FIR - Eduardo, Sanchez Vergaray IR - Eduardo SV FIR - Elena, Belonosova IR - Elena B FIR - Lenar, Sultanov IR - Lenar S FIR - Elvira, Ivanova IR - Elvira I FIR - Alexey, Yakovlev IR - Alexey Y FIR - Alexander, Panteleev IR - Alexander P FIR - Rodney, Dawson IR - Rodney D FIR - Gulam, Latiff IR - Gulam L FIR - Lerato, Mohapi IR - Lerato M FIR - Jantjie, Taljaard IR - Jantjie T FIR - Johannes, Jurgens Lombaard IR - Johannes JL FIR - Mohammed, Khan IR - Mohammed K FIR - Ebrahim, Variava IR - Ebrahim V FIR - Ploenchan, Chetchotisakd IR - Ploenchan C FIR - Sasisopin, Kiertiburanakul IR - Sasisopin K FIR - Anchalee, Avihingsanon IR - Anchalee A EDAT- 2019/03/29 06:00 MHDA- 2021/01/07 06:00 CRDT- 2019/03/29 06:00 PHST- 2018/11/08 00:00 [received] PHST- 2019/04/05 00:00 [accepted] PHST- 2019/03/29 06:00 [pubmed] PHST- 2021/01/07 06:00 [medline] PHST- 2019/03/29 06:00 [entrez] AID - 5421214 [pii] AID - 10.1093/cid/ciz256 [doi] PST - ppublish SO - Clin Infect Dis. 2020 Feb 3;70(4):549-556. doi: 10.1093/cid/ciz256.