Drug-drug interactions between antiretrovirals and bedaquiline

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dc.contributor.advisorCoetzee, Daviden_ZA
dc.contributor.authorPandie, Mishalen_ZA
dc.date.accessioned2018-02-07T12:11:42Z
dc.date.available2018-02-07T12:11:42Z
dc.date.issued2017en_ZA
dc.description.abstractTuberculosis (TB) is a leading cause of morbidity and mortality worldwide. People living with HIV are particularly susceptible to TB infection, and treatment of HIV-TB co-infection is challenging for multiple reasons, including potential drug-interactions. Drug-resistant TB is difficult to treat and is associated with high treatment failure rates, mainly because the antimycobacterial drugs currently available are ineffective against drug-resistant TB. Bedaquiline is a new antimycobacterial drug which has shown great promise through its excellent efficacy for treating drug-resistant TB. Being a new drug, however, potential drug interactions with antiretrovirals are a major concern. Bedaquiline is metabolized in the liver by an enzyme called cytochrome P450 3A (CYP3A). The antiretrovirals nevirapine, efavirenz, and lopinavir/ritonavir (LPV/r) can affect the activity of this enzyme, and consequently affect the concentration of bedaquiline in the patient's blood. Nevirapine and efavirenz increase the activity of CYP3A, which may result in increased metabolism of bedaquiline, thus decreasing the concentration of bedaquiline, with consequent risk of treatment failure or the further development of drug-resistance. LPV/r inhibits the CYP3A enzyme, which may result in decreased bedaquiline metabolism, thus causing high concentration of bedaquiline in the blood, with consequent risk of toxicity. We conducted a pharmacokinetic study in 43 adult patients with drug-resistant TB to evaluate the drug-interactions between bedaquiline and the antiretrovirals nevirapine and LPV/r. We did serial measurements of the bedaquiline concentration in their plasma over 48 hours, and compared these concentrations in patients who were on antiretroviral and those who were not on antiretrovirals. Our results showed that nevirapine had no significant effect on bedaquiline concentrations, while patients on LPV/r had bedaquiline concentrations 2 fold higher than patients not on antiretrovirals. We could not determine the clinical significance of this, but recommend that patients receiving LPV/r and bedaquiline in combination must be closely monitored for side-effects.en_ZA
dc.identifier.apacitationPandie, M. (2017). <i>Drug-drug interactions between antiretrovirals and bedaquiline</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine. Retrieved from http://hdl.handle.net/11427/27401en_ZA
dc.identifier.chicagocitationPandie, Mishal. <i>"Drug-drug interactions between antiretrovirals and bedaquiline."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2017. http://hdl.handle.net/11427/27401en_ZA
dc.identifier.citationPandie, M. 2017. Drug-drug interactions between antiretrovirals and bedaquiline. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Pandie, Mishal AB - Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. People living with HIV are particularly susceptible to TB infection, and treatment of HIV-TB co-infection is challenging for multiple reasons, including potential drug-interactions. Drug-resistant TB is difficult to treat and is associated with high treatment failure rates, mainly because the antimycobacterial drugs currently available are ineffective against drug-resistant TB. Bedaquiline is a new antimycobacterial drug which has shown great promise through its excellent efficacy for treating drug-resistant TB. Being a new drug, however, potential drug interactions with antiretrovirals are a major concern. Bedaquiline is metabolized in the liver by an enzyme called cytochrome P450 3A (CYP3A). The antiretrovirals nevirapine, efavirenz, and lopinavir/ritonavir (LPV/r) can affect the activity of this enzyme, and consequently affect the concentration of bedaquiline in the patient's blood. Nevirapine and efavirenz increase the activity of CYP3A, which may result in increased metabolism of bedaquiline, thus decreasing the concentration of bedaquiline, with consequent risk of treatment failure or the further development of drug-resistance. LPV/r inhibits the CYP3A enzyme, which may result in decreased bedaquiline metabolism, thus causing high concentration of bedaquiline in the blood, with consequent risk of toxicity. We conducted a pharmacokinetic study in 43 adult patients with drug-resistant TB to evaluate the drug-interactions between bedaquiline and the antiretrovirals nevirapine and LPV/r. We did serial measurements of the bedaquiline concentration in their plasma over 48 hours, and compared these concentrations in patients who were on antiretroviral and those who were not on antiretrovirals. Our results showed that nevirapine had no significant effect on bedaquiline concentrations, while patients on LPV/r had bedaquiline concentrations 2 fold higher than patients not on antiretrovirals. We could not determine the clinical significance of this, but recommend that patients receiving LPV/r and bedaquiline in combination must be closely monitored for side-effects. DA - 2017 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Drug-drug interactions between antiretrovirals and bedaquiline TI - Drug-drug interactions between antiretrovirals and bedaquiline UR - http://hdl.handle.net/11427/27401 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/27401
dc.identifier.vancouvercitationPandie M. Drug-drug interactions between antiretrovirals and bedaquiline. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2017 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/27401en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherEpidemiologyen_ZA
dc.subject.otherantiretroviral therapyen_ZA
dc.titleDrug-drug interactions between antiretrovirals and bedaquilineen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMPHen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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