A phase IIIb, randomized, open-label study of the safety and efficacy of Dolutegravir or Efavirenz each administered with two NRTIs in HIV-1-infected antiretroviral therapy-naïve adults starting treatment for Rifampicin-sensitive tuberculosis

Project no.: HIV-NAT 214/ING117175 (NCT02178592)

This is a Phase IIIb, randomized, open-label study describing the efficacy and safety of DTG and EFV-containing ART regimens in HIV/TB co-infected patients. This study is designed to assess the antiviral activity of DTG or efavirenz (EFV) ART-containing regimens through 48 weeks.

Results: Of 113 subjects enrolled, 69 were randomised to DTG and 44 to EFV. Median baseline HIV-1 RNA and CD4+ cell counts were 5.10 log10 c/mL and 208 cells/µL in the DTG arm and 5.24 log10 c/mL and 202 cells/µL in the EFV arm; 40% were women. The proportions of subjects with HIV-1-RNA < 50 c/mL at Week 24 were 56/69 (81%) (95% CI: 72%, 90%) in the DTG arm and 39/44 (89%) (95% CI: 79%, 98%) in the EFV arm. The lower DTG response rate was driven by non-treatment related snapshot failures: five participants (7%) in DTG arm and none in EFV arm discontinued due to non-treatment-related reasons (loss to follow-up/protocol deviations). Median CD4+ cell increases at Week 24 were 146 cells/µL (IQR: 71, 214) for DTG and 93 cells/µL (IQR: 47, 178) for EFV. Two subjects discontinued study treatment due to AEs (both on EFV). TB-Associated IRIS rates (adjudicated and investigator reported) were low (DTG, n = 4 [6%]; EFV, n = 4 [9%]). No subjects discontinued due to IRIS or liver events.

Interim Week 24 results from this ongoing study show that DTG 50 mg twice daily appears to be effective and well-tolerated in HIV/TB co-infected adults receiving RIF-based TB therapy. Rates of IRIS were low. There were no new toxicity signals for DTG and no discontinuations due to liver events. These data support the use of DTG based regimen in HIV/TB co-infection.

(Source: Dooley K, et al., Safety and efficacy of dolutegravir-based ART in TB/HIV coinfected adults at week 24. Abstract #33. Presented at CROI 2018)