Browsing by Author "Gustafsson, Lars L."
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Item CD4-T-Lymphocyte Reference Ranges in Uganda and Its Influencing Factors(Laboratory Medicine, 2011) Nanzigu, Sarah; Waako, Paul; Petzold, Max; Kiwanuka, Gertrude; Dungu, Henry; Makumbi, Fred; Gustafsson, Lars L.; Eriksen, JaranGiven the importance of CD4-T-lymphocyte monitoring in HIV/ART management, we established CD4/CD8 reference ranges in Uganda and studied factors associated with CD4/CD8 in a normal population. Blood samples for 206 HIV seronegative healthy volunteers from the Mbarara and Kampala districts in Uganda were analyzed using the PanLeucogating protocol.Item Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination(Malaria journal, 2009) Ntale, Muhammad; Obua, Celestino; Mukonzo, Jackson; Mahindi, Margarita; Gustafsson, Lars L.; Beck, Olof; Ogwal- Okeng, Jasper W.Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem® (artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper. Methods: Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood. Results: The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed. Conclusion: The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.Item 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, EleniHIV 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.Item 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, EleniEfavirenz, 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