Research in context
dolutegravir-based, tuberculosis
TUBERCULOSIS

We searched PubMed for clinical studies on the dosing of dolutegravir with rifampicin-based antituberculosis therapy published between Jan 1, 2010, and Oct 10, 2022, using the search terms (“tuberculosis” AND “dolutegravir” AND “HIV”) with no language restrictions. Our search yielded one non-comparative randomised trial and one retrospective observational cohort study. INSPIRING was a non-comparative, active control, randomised, open-label study among people living with HIV who were naive to antiretroviral therapy (ART) with CD4 counts of at least 50 cells per μL. Participants were randomly assigned to receive either dolutegravir-based or efavirenz-based ART. Dolutegravir was dosed at 50 mg twice daily during and for 2 weeks after antituberculosis therapy. Week 48 virological suppression (HIV-1 RNA <50 copies per mL) in INSPIRING was reported in 75% (52/69) of participants in the supplemental dolutegravir group and 82% (36/44) of participants in the efavirenz group. These results support the hypothesis that twice-daily dolutegravir is effective for people with HIV who are on rifampicin-based antituberculosis therapy. Twice-daily dolutegravir was well tolerated. Although INSPIRING generated high-quality evidence, the study was not powered for between-arm comparisons. A retrospective observational cohort study in Botswana reported on the viral load suppression rates achieved with dolutegravir-based ART in people with HIV who were co-infected with tuberculosis under programmatic conditions. A high proportion of patients (322 [44%] of 739) received once-daily dolutegravir instead of the twice-daily dosing recommended in their national guidelines, which indicates the difficulty of implementing supplemental dolutegravir dosing in a high-burden setting. Virological suppression, which was determined while participants were on antituberculosis therapy, was reported in 204 (95%) of 214 individuals in the once-daily dosing group and in 241 (95%) of 254 individuals in the twice-daily dosing group. The risk of bias is high in retrospective cohort studies but the relatively large sample size and the almost identical viral suppression rates in the two dolutegravir dosing groups suggest that supplemental dolutegravir dosing might be unnecessary for people with HIV on rifampicin-based antituberculosis therapy.
To our knowledge, RADIANT-TB is the first randomised trial to assess the need for twice-daily dosing with dolutegravir when co-administered with rifampicin-based antituberculosis therapy. We found similar rates of virological suppression in both dolutegravir dosing arms. None of the participants who had study-defined virological failure developed treatment-emergent integrase strand transfer inhibitor resistance and no major safety issues were reported in either arm. Our findings suggest that twice-daily dolutegravir dosing with rifampicin-based antituberculosis therapy might be unnecessary, but we did not have the power to compare outcomes by study arm.
The findings of our study together with those of the Botswanan retrospective cohort study suggest that once-daily dolutegravir is as effective as twice-daily dolutegravir for virological suppression in patients on rifampicin co-treatment for tuberculosis.We aimed to determine whether virological outcomes with standard-dose dolutegravir-based ART would be acceptable in people with HIV on rifampicin-based antituberculosis therapy.