Publication
Decreased Dolutegravir and Efavirenz Concentrations With Preserved Virological Suppression in Patients With Tuberculosis and Human Immunodeficiency Virus Receiving High-Dose Rifampicin
Publisher:
Oxford University Press (OUP)
Date:
21-07-2022
DOI:
10.1093/CID/CIAC585
Abstract: Higher doses of rif icin may improve treatment outcomes and reduce the duration of tuberculosis (TB) therapy. However, drug–drug interactions with antiretroviral therapy (ART) and safety in people with human immunodeficiency virus (HIV) have not been evaluated. This was a randomized, open-label trial where newly diagnosed TB patients were randomized to higher (35 mg/kg) or standard (10 mg/kg) daily-dose rif icin. ART treatment–naive patients were randomized to dolutegravir- or efavirenz-based ART. At week 6, trough dolutegravir or mid-dose efavirenz plasma concentrations were assayed. HIV viral load was measured at week 24. Among 128 patients randomized, the median CD4 count was 191 cells/mm3. The geometric mean ratio (GMR) for trough dolutegravir concentrations on higher- vs standard-dose rif icin was 0.57 (95% confidence interval [CI], .34–.97 P = .039) and the GMR for mid-dose efavirenz was 0.63 (95% CI, .38–1.07 P = .083). There was no significant difference in attainment of targets for dolutegravir trough or efavirenz mid-dose concentrations between rif icin doses. The incidence of HIV treatment failure at week 24 was similar between rif icin doses (14.9% vs 14.0%, P = .901), as was the incidence of drug-related grade 3–4 adverse events (9.8% vs 6%). At week 8, fewer patients remained sputum culture positive on higher-dose rif icin (18.6% vs 37.0%, P = .063). Compared with standard-dose rif icin, high-dose rif icin reduced dolutegravir and efavirenz exposures, but HIV suppression was similar across treatment arms. Higher-dose rif icin was well tolerated among people with HIV and associated with a trend toward faster sputum culture conversion. NCT03982277.