Dolutegravir-based Antiretroviral Therapy for Patients Coinfected With Tuberculosis and Human Immunodeficiency Virus: A Multicenter, Noncomparative, Open-label, Randomized Trial

Abstract

Background The concurrent treatment of tuberculosis and human immunodeficiency virus (HIV) is challenging, owing to drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir (DTG) were assessed in adults with HIV and drug-susceptible tuberculosis. Methods International Study of Patients with HIV on Rifampicin ING is a noncomparative, active-control, randomized, open-label study in HIV-1–infected antiretroviral therapy–naive adults (CD4+ ≥50 cells/mm3). Participants on rifampicin-based tuberculosis treatment ≤8 weeks were randomized (3:2) to receive DTG (50 mg twice daily both during and 2 weeks after tuberculosis therapy, then 50 mg once daily) or efavirenz (EFV; 600 mg daily) with 2 nucleoside reverse transcriptase inhibitors for 52 weeks. The primary endpoint was the proportion of DTG-arm participants with plasma HIV-1-RNA <50 copies/mL (responders) by the Food and Drug Administration Snapshot algorithm (intent-to-treat exposed population) at Week 48. The study was not powered to compare arms. Results For DTG (n = 69), the baseline HIV-1 RNA was >100 000 copies/mL in 64% of participants, with a median CD4+ count of 208 cells/mm3; for EFV (n = 44), 55% of participants had HIV-1 RNA >100 000 copies/mL, with a median CD4+ count of 202 cells/mm3. The Week 48 response rates were 75% (52/69, 95% confidence interval [CI] 65–86%) for DTG and 82% (36/44, 95% CI 70–93%) for EFV. The DTG nonresponses were driven by non–treatment related discontinuations (n = 10 lost to follow-up). There were no deaths or study drug switches. There were 2 discontinuations for toxicity (EFV). There were 3 protocol-defined virological failures (2 DTG, no acquired resistance; 1 EFV, emergent resistance to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors). The tuberculosis treatment success rate was high. Tuberculosis-associated IRIS was uncommon (4/arm), with no discontinuations for IRIS. Conclusions Among adults with HIV receiving rifampicin-based tuberculosis treatment, twice-daily DTG was effective and well tolerated. Clinical Trials Registration NCT02178592.

Neurotoxicities in the treatment of HIV between dolutegravir, rilpivirine and dolutegravir/rilpivirine: a meta-analysis

“…A total of 20 studies met the inclusion criteria to be included in the meta-analysis. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] The results include 5 studies for rilpivirine, [16][17][18][19][20] 14 studies for dolutegravir [21][22][23][24][25][26][27][28][29][30][31][32][33][34] and 1 study for dolutegravir/rilpivirine. 35 The total number of represented patients was 10 988 with the majority being male.…”

Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials

“…In the ANRS 12,180 [37,38] and ANRS 12,300 [39,40] trials, RAL plus TDF/3TC was compared with EFV plus TDF/3TC. While in the INSPIRING [41,42] trial, DTG was compared with EFV plus major TDF/FTC, or plus other two N(t)RTIs. Drug doses of INIs (i.e.…”

Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

“…20,28 This has important implications for our findings, as dolutegravir will likely overcome the high levels of NNRTI resistance, has high barriers to resistance and can be co-administered with TB treatment. 29,30 However, the high prevalence of NRTI resistance (68% resistant to three or more NRTIs) suggest significant numbers could be on functional dolutegravir monotherapy. Data from the EARNEST trial demonstrated that even in the presence of predicted NRTI resistance, virological suppression with PI and NRTI based-regimens was good (89%).…”