Browsing by Author "Mukonzo, Jackson K."

Now showing 1 - 5 of 5
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    Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study
    (BMC Infectious Diseases, 2013) Mukonzo, Jackson K.; Okwera, Alphonse; Nakasujja, Neoline; Luzze, Henry; Sebuwufu, Deogratious; Ogwal-Okeng, Jasper; Waako, Paul; Gustafsson, Lars L.; Aklillu, Eleni
    HIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection. Methods: 197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes for CYP2B6 (*6, *11), CYP3A5 (*3, *6, *7), ABCB1 (c.3435C>T and c.4036 A/G rs3842), CYP2A6 (*9, *17) and NR1I3 rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score.
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    Markov Model for Characterizing Neuropsychologic Impairment and Monte Carlo Simulation for Optimizing Efavirenz Therapy
    (The Journal of Clinical Pharmacology, 2015) Bisaso Kuteesa, Ronald; Mukonzo, Jackson K.; Ette, Ene I.
    The study was undertaken to develop a pharmacokinetic-pharmacodynamic model to characterize efavirenz-induced neuropsychologic impairment, given preexistent impairment, which can be used for the optimization of efavirenz therapy via Monte Carlo simulations. The modeling was performed with NONMEM 7.2. A 1-compartment pharmacokinetic model was fitted to efavirenz concentration data from 196 Ugandan patients treated with a 600-mg daily efavirenz dose. Pharmacokinetic parameters and area under the curve (AUC) were derived. Neuropsychologic evaluation of the patients was done at baseline and in week 2 of antiretroviral therapy. A discrete-time 2-state first-order Markov model was developed to describe neuropsychologic impairment. Efavirenz AUC, day 3 efavirenz trough concentration, and female sex increased the probability (P01) of neuropsychologic impairment. Efavirenz oral clearance (CL/F) increased the probability (P10) of resolution of preexistent neuropsychologic impairment. The predictive performance of the reduced (final) model, given the data, incorporating AUC on P01and CL /F on P10, showed that the model adequately characterized the neuropsychologic impairment observed with efavirenz therapy. Simulations with the developed model predicted a 7% overall reduction in neuropsychologic impairment probability at 450 mg of efavirenz. We recommend a reduction in efavirenz dose from 600 to 450 mg, because the 450-mg dose has been shown to produce sustained antiretroviral efficacy
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    A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans
    (British journal of clinical pharmacology, 2009) Mukonzo, Jackson K.; Röshammar, Daniel; Waako, Paul; Andersson, Maria; Fukasawa, Takashi; Milani, Lili; Svensson, Jan Olof; Ogwal-Okeng, Jasper; Gustafsson, Lars L.; Aklillu, Eleni
    Efavirenz, a potent antiretroviral agent, is the cornerstone of highly active antiretroviral therapy (HAART), particularly in human immunodeficiency virus (HIV) and tuberculosis co-infected patients being co-treated with rifampicin. Its essential role as an affordable HAART treatment in resource-poor countries is due to its relatively low cost, manageable pill burden and solid efficacy as well as safety documentation
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    Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum
    (Clinical Infectious Diseases, 2018) Lamorde, Mohammed; Wang, Xinzhu; Neary, Megan; Bisdomini, Elisa; Nakalema, Shadia; Byakika-Kibwika, Pauline; Mukonzo, Jackson K.; Khan, Waheed; Owen, Andrew; McClure, Myra; Boffito, Marta
    A clinical trial showed that efavirenz 400 mg once daily (EFV400) is as effective as the standard adult dose. World Health Organization recommends EFV400 as an alternative first-line agent, but data are lacking in the third trimester of pregnancy (TT). We investigated the pharmacokinetics, efficacy, and CYP2B6 pharmacogenetics in HIV-infected women (WLWH) on EFV400 during TT and post-partum (PP). Methods. An open-label 2-center study (United Kingdom, Uganda) was conducted in WLWH receiving antiretroviral regimens containing efavirenz 600 mg, who had their efavirenz dose reduced to EFV400. Weekly therapeutic drug monitoring (TDM), steadystate pharmacokinetic profiles (TT and PP), safety, virological efficacy, and CYP2B6 polymorphisms at positions 516 (C > T) and 938 (T > C) were evaluated.
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    Suboptimal Antiretroviral Drug Levels and Virologic Failures among PLHIV at a Rural Referral Hospital in South Western Uganda: A Descriptive Crosssectional Study
    (Research Square, 2020) Samba Twinomujuni, Silvano; Engeu Ogwang, Patrick; Roelofsen, Felicitas; Mukonzo, Jackson K.; Atukunda, Esther C.
    Achieving favorable HIV treatment outcomes is a major challenge, particularly due to nonadherence and consequent sub-therapeutic plasma antiretroviral drug levels. This is often complicated by the development of resistant strains due to mutations. Monitoring antiretroviral drug levels in the blood of patients enrolled on ART can reveal if levels are too high, enough, or too low. High levels may lead to dose-dependent side effects and sub-therapeutic levels could promote treatment failure and resistance. In Uganda, as part of routine HIV care, plasma antiretroviral drug level is estimated indirectly by clinic-based pill counts and patient self-reported adherence, which give no evidence of ingested medication. This study aimed at exploring steady-state nevirapine and efavirenz drug levels in HIV patients accessing ART at a rural referral hospital in South Western Uganda. Methods: This study was nested into a randomized clinical trial that evaluated the effect of Artemisia annua L. and Moringa oleifera on immunological response and viral load among persons living with HIV (PLHIV). In the parent study, 250 HIV-infected patients with continued immunologic suppression (CD4 count < 350cells/μL) despite a minimum of one-year on ART were enrolled. Out of 250 clinical trial participants, 95 were randomly selected for steady-state efavirenz and nevirapine plasma concentration sampling having taken the last at bedtime. Additionally, CD4 count, HIV load, liver, and renal function tests were determined. Participants were also interviewed for adherence, and factors that affect blood drug levels.