Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/32451
Title: Dolutegravir-based antiretroviral therapy for patients co-infected with tuberculosis and HIV: 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
Affilliation: Johns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA.
Desmond Tutu HIV Foundation. Cape Town, South Africa.
Clinical HIV Research Unit. Johannesburg, South Africa.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Hospital Nacional Dos de Mayo. Lima, Peru / Universidad Nacional Mayor de San Marcos. Lima, Peru.
Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil /Tropical Medicine Foundation Dr Heitor Vieira Dourado. Manaus, AM, Brazil.
Fundación Huésped. Buenos Aires, Argentina.
Regional Center For Prevention and Treatment of AIDS and Infectious Diseases. Moscow, Russia.
ViiV Healthcare Ltd. Brentford, UK.
GlaxoSmithKline. Stockley Park. Uxbridge, UK.
ViiV Healthcare Ltd. Melbourne, Victoria, Australia.
GlaxoSmithKline. Collegeville, PA, USA.
ViiV Healthcare. Research Triangle Park. NC, USA.
ViiV Healthcare. Research Triangle Park. NC, USA.
ViiV Healthcare Ltd. Brentford, UK.
ViiV Healthcare Ltd. Brentford, UK.
Abstract: Background: Concurrent treatment of tuberculosis and HIV is challenging owing to drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir were assessed in adults with HIV and drug-susceptible tuberculosis. Methods: INSPIRING (NCT02178592) is a non-comparative, active-control, randomised, open-label study in HIV1-infected ART-naïve adults (CD4+ 50 cells/mm3 ). Participants on rifampicin-based tuberculosis treatment ≤8 weeks were randomised (3:2) to receive dolutegravir (50 mg twice-daily during and 2 weeks post-tuberculosis therapy, then 50 mg once-daily) or efavirenz (600 mg daily), with two NRTIs for 52 weeks. The primary endpoint was the proportion of dolutegravir-arm participants with plasma HIV-1-RNA <50 copies/mL (responders) by FDA Snapshot algorithm (intent-to-treat exposed population) at Week 48. The study was not powered to compare arms. Results: For dolutegravir (N=69), Baseline HIV-1-RNA was >100,000 copies/mL in 64%, with median CD4+ 208 cells/mm3 ; for efavirenz (N=44), 55% had HIV-1-RNA >100,000 copies/mL, median CD4+ count was 202 cells/mm3 . Week 48 response rate was 75% (52/69) (95% CI: 65%, 86%) for dolutegravir and 82% (36/44) (95% CI: 70%, 93%) for efavirenz. Dolutegravir non-response was driven by non-treatmentrelated discontinuations (n=10 lost-to-follow-up). There were no deaths or study drug switches. There were two discontinuations for toxicity (efavirenz). There were three protocol-defined virological failures (2 dolutegravir, no acquired resistance; 1 efavirenz, NRTI and NNRTI emergent resistance). Tuberculosis treatment success was high. TB-associated IRIS was uncommon (4/arm), with no discontinuations for IRIS. Conclusions: Among adults with HIV receiving rifampicin-based tuberculosis treatment, twice-daily dolutegravir was effective and well-tolerated.
Keywords: HIV
Tuberculosis
Dolutegravir
Efavirenz
Immune reconstitution inflammatory syndrome
Issue Date: 2019
Publisher: Oxford University Press
Citation: DOOLEY, Kelly E. et al. Dolutegravir-based antiretroviral therapy for patients co-infected with tuberculosis and HIV: a multicenter, noncomparative, open-label, randomized trial. Clinical Infectious Diseases, p. 1-20, Mar. 2019.
DOI: 10.1093/cid/ciz256
ISSN: 1058-4838
Copyright: restricted access
Appears in Collections:AM - ILMD - Artigos de Periódicos
INI - Artigos de Periódicos

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