@article{Griesel2023,
abstract = {Summary Background The drug–drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, which is difficult to implement in high-burden settings. We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy. Methods RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per $\mu$L, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first 2 months followed by isoniazid and rifampicin for 4 months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA Findings Between Nov 28, 2019, and July 23, 2021, 108 participants (38 female, median age 35 years [IQR 31–40]) were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per $\mu$L (IQR 145–316) and median HIV-1 RNA was 5{\textperiodcentered}2 log10 copies per mL (4{\textperiodcentered}6–5{\textperiodcentered}7). At week 24, 43 (83{\%}, 95{\%} CI 70–92) of 52 participants in the supplemental dolutegravir arm and 44 (83{\%}, 95{\%} CI 70–92) of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4{\%}]), insomnia (3/108 [3{\%}]), and pneumonia (3/108 [3{\%}]). Interpretation Our findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis. Funding Wellcome Trust.},
author = {Griesel, Rulan and Zhao, Ying and Simmons, Bryony and Omar, Zaayid and Wiesner, Lubbe and Keene, Claire M and Hill, Andrew M and Meintjes, Graeme A and Maartens, Gary},
doi = {10.1016/S2352-3018(23)00081-4},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Griesel et al. - 2023 - Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB) a phas.pdf:pdf},
issn = {2352-3018},
journal = {The Lancet HIV},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {may},
number = {7},
pages = {e433--e441},
pmid = {37230101},
publisher = {Elsevier},
title = {{Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB): a phase 2, non-comparative, randomised controlled trial}},
url = {http://www.thelancet.com/article/S2352301823000814/fulltext http://www.thelancet.com/article/S2352301823000814/abstract https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(23)00081-4/abstract},
volume = {10},
year = {2023}
}

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Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per $μ$L, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first 2 months followed by isoniazid and rifampicin for 4 months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA Findings Between Nov 28, 2019, and July 23, 2021, 108 participants (38 female, median age 35 years [IQR 31–40]) were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per $μ$L (IQR 145–316) and median HIV-1 RNA was 5˙2 log10 copies per mL (4˙6–5˙7). At week 24, 43 (83%, 95% CI 70–92) of 52 participants in the supplemental dolutegravir arm and 44 (83%, 95% CI 70–92) of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4%]), insomnia (3/108 [3%]), and pneumonia (3/108 [3%]). Interpretation Our findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis. 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We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy. Methods RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per $\\mu$L, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. 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