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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dc.contributor.authorSekaggya-Wiltshire, Christine
dc.contributor.authorNabisere, Ruth
dc.contributor.authorMusaazi, Joseph
dc.contributor.authorOtaalo, Brian
dc.contributor.authorAber, Florence
dc.contributor.authorAlinaitwe, Lucy
dc.contributor.authorNampala, Juliet
dc.contributor.authorNajjemba, Letisha
dc.contributor.authorBuzibye, Allan
dc.contributor.authorOmali, Denis
dc.contributor.authorGausi, Kamunkhwala
dc.contributor.authorKengo, Allan
dc.contributor.authorLamorde, Mohammed
dc.contributor.authorAarnoutse, Rob
dc.contributor.authorDenti, Paolo
dc.contributor.authorDooley, Kelly E.
dc.contributor.authorSloan, Derek J.
dc.date.accessioned2023-03-03T17:22:46Z
dc.date.available2023-03-03T17:22:46Z
dc.date.issued2022
dc.description.abstractHigher 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.en_US
dc.identifier.citationSekaggya-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/ciac585en_US
dc.identifier.urihttps://doi.org/10.1093/cid/ciac585
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/8065
dc.language.isoenen_US
dc.publisherClinical Infectious Diseasesen_US
dc.subjectTB-HIVen_US
dc.subjectHigh-dose rifampicinen_US
dc.subjectAntiretroviral therapyen_US
dc.subjectDolutegraviren_US
dc.subjectEfavirenzen_US
dc.titleDecreased Dolutegravir and Efavirenz Concentrations With Preserved Virological Suppression in Patients With Tuberculosis and Human Immunodeficiency Virus Receiving High-Dose Rifampicinen_US
dc.typeArticleen_US
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