Population pharmacokinetic models describing drug-drug interactions and variability in HIV infected South Africans on protease inhibitor-based antiretroviral regimens with and without tuberculosis

Abstract

Lopinavir/ritonavir is an important component of the first-line and second-line antiretroviral treatment for young children and adults respectively in the current World Health Organization guidelines. Rifampicin, a key component of antituberculosis treatment, profoundly reduces lopinavir concentrations. Therefore, investigation of the optimal dosage regimens of lopinavir/ritonavir when co-administered with rifampicin-based antituberculosis treatment is needed urgently. Moreover, treatment adherence is associated with virological and clinical responses to antiretroviral treatment, and reduced adherence leads to the development of drug resistance. The projects in this thesis were designed to characterize the population pharmacokinetic parameters of lopinavir and ritonavir in HIV infected South Africans, to account for the drug-drug interactions between lopinavir, ritonavir and rifampicin, to investigate optimal dose regimens of lopinavir/ritonavir when administered with rifampicin, and to investigate new approach to evaluate adherence.