by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

June 6, 2023

Featured Literature:

Griesel R, Zhao Y, Simmons B, et. al.  Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB): a phase 2, non-comparative, randomised controlled trial.  Lancet HIV.  2023 May 22;S2352-3018(23)00081-4.  PMID: 37230101.    

This single-site study examined week 24 virologic outcomes among 108 adults receiving standard-dose dolutegravir-based ART and rifampicin-based antituberculosis therapy.  Participants were either ART-naïve (81%) or first-line ART interrupted (19%), and on rifampicin-based therapy for less than 3 months.  Participants received either supplemental dolutegravir 50mg or placebo (taken 12 hours after 300mg TDF plus 300mg 3TC plus 50mg DTG).  Standard tuberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol was administered for the first 2 months, followed by isoniazid plus rifampicin for 4 months; supplemental dolutegravir or placebo was continued for 2 weeks after antituberculosis therapy was stopped.  Plasma samples were also collected for dolutegravir trough concentrations and dried blood spots for tenofovir diphosphate.  Overall, 43/52 (83%) receiving supplemental dolutegravir vs. 44/53 (83%) receiving placebo had viral load < 50 copies/mL at week 24.  Among ART-naïve participants, 36/43 (84%) in the supplemental dolutegravir arm vs. 36/42 (86%) in the placebo arm had VL < 50 copies/mL.  In participants with prior first-line interrupted ART, 7/9 (78%) in the supplemental dolutegravir arm vs. 8/11 (73%) in the placebo arm had VL < 50 copies/mL.  Overall, 6/9 (67%) and 5/9 (56%) of participants in the supplemental dolutegravir arm and placebo arm, respectively, had VL 50-999 copies/mL.  In the 19 participants with protocol-defined virological failure, no treatment-emergent INSTI resistance mutations were detected up to week 48.  No significant differences were observed with regard to Grade 3 and 4 adverse events.

Author’s Commentary:

Findings from this randomized trial add to prior retrospective cohort, dose-ranging, and pharmacokinetic studies which suggest that twice-daily dolutegravir dosing with rifampicin-based antituberculosis therapy may not be necessary.  These observations may be particularly valuable for resource-limited settings with high prevalence of HIV and tuberculosis.  However, because this study was not powered for formal between-arm efficacy comparison, further trials (e.g. phase 3) and/or large cohort analyses may be needed to prompt changes in established guidelines and clinical practice.  Future studies should also include people with prior ART treatment (who may or may not have NRTI and/or INSTI resistance associated mutations) to help generalize these findings even further.

The author has no conflicts of interest to disclose.

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