Kelly E Dooley1, Richard Kaplan2, Noluthando Mwelase3, Beatriz Grinsztejn4, Eduardo Ticona5, Marcus Lacerda6, Omar Sued7, Elena Belonosova8, Mounir Ait-Khaled9, Konstantinos Angelis10, Dannae Brown11, Rajendra Singh12, Christine L Talarico13, Allan R Tenorio13, Michael R Keegan9, Michael Aboud9. 1. Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Desmond Tutu Human Immunodeficiency Virus (HIV) Foundation, Cape Town. 3. Clinical HIV Research Unit, Johannesburg, South Africa. 4. Instituto de Pesquisa Clínica Evandro Chagas Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. 5. Hospital Nacional Dos de Mayo, Universidad Nacional Mayor de San Marcos, Lima, Peru. 6. Instituto Leônidas & Maria Deane (Fiocruz)/Tropical Medicine Foundation Dr Heitor Vieira Dourado, Manaus, Brazil. 7. Fundación Huésped, Buenos Aires, Argentina. 8. Regional Center For Prevention and Treatment of Acquired Immunodeficiency Syndrome and Infectious Diseases, Orel, Russia. 9. ViiV Healthcare Ltd., Brentford. 10. GlaxoSmithKline, Uxbridge, United Kingdom. 11. ViiV Healthcare Ltd., Melbourne, Victoria, Australia. 12. GlaxoSmithKline, Collegeville, Pennsylvania. 13. ViiV Healthcare, Research Triangle Park, North Carolina.
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 onRifampicin 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 receivingrifampicin-based tuberculosis treatment, twice-daily DTG was effective and well tolerated. CLINICAL TRIALS REGISTRATION: NCT02178592.
RCT Entities:
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.
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