Decreased Dolutegravir and Efavirenz Concentrations With Preserved Virological Suppression in Patients With Tuberculosis and Human Immunodeficiency Virus Receiving High-Dose Rifampicin
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Clinical Infectious Diseases
Abstract
Higher doses of rifampicin 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.
Methods. 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 rifampicin. 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.
Results. 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 rifampicin 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 rifampicin doses. The incidence of
HIV treatment failure at week 24 was similar between rifampicin 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 higherdose
rifampicin (18.6% vs 37.0%, P =.063).
Conclusions. Compared with standard-dose rifampicin, high-dose rifampicin reduced dolutegravir and efavirenz exposures,
but HIV suppression was similar across treatment arms. Higher-dose rifampicin was well tolerated among people with HIV and
associated with a trend toward faster sputum culture conversion.
Description
Keywords
TB-HIV, High-dose rifampicin, Antiretroviral therapy, Dolutegravir, Efavirenz
Citation
Sekaggya-Wiltshire, C., Nabisere, R., Musaazi, J., Otaalo, B., Aber, F., Alinaitwe, L., ... & Sloan, D. J. (2022). Decreased Dolutegravir and Efavirenz Concentrations With Preserved Virological Suppression in Patients With Tuberculosis and Human Immunodeficiency Virus Receiving High-Dose Rifampicin. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciac585