Dolutegravir-Based Antiretroviral Therapy for Patients Co-Infected with Tuberculosis and Hiv: A Multicenter, Noncomparative, Open-Label, Randomized Trial.

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 HIV-1-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-treatment-related 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.