Browsing by Author "Mugyenyi, P."
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Item Cytochrome P450 2B6 (CYP2B6) G516T influences Nevirapine Plasma Concentrations in HIV-infected Patients in Uganda(HIV medicine, 2007) Penzak, S.R.; Kabuye, G.; Mugyenyi, P.; Mbamanya, F.; Natarajan, V.; Kityo, C.; Formentini, E.; Masur, H.Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV-infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this population. We aimed to determine the influence of CYP2B6 genotype at position 516 on nevirapine trough concentrations in HIV-infected patients in Kampala, Uganda. Additional polymorphisms in the CYP and multidrug resistance protein-1 (MDR-1) genes were also assessed for their impact on nevirapine concentrations.Item Daily Co-Trimoxazole Prophylaxis in Severely Immunosuppressed HIV-Infected Adults in Africa Started on Combination Antiretroviral Therapy: An Observational Analysis of the DART Cohort(The Lancet, 2010) Walker, A.S.; Munderi, P.; Katabira, E.; Mugyenyi, P.; Ssali, F.; Hakim, J.; Babiker, A. G.Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68]. Our results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks for all adults starting combination ART in Africa.Item A Randomized Trial of Punctuated Antiretroviral Therapy in Ugandan HIV-Seropositive Adults With Pulmonary Tuberculosis and CD41 T-Cell Counts of $350 cells/lL(Journal of Infectious Diseases, 2011) Nanteza, M. W.; Mayanja-Kizza, H.; Mupere, E.; Mugyenyi, P.; Mugerwa, R. D.; Havlir, D. V.Optimal treatment of human immunodeficiency virus (HIV)–associated tuberculosis in patients with high CD4+ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression. We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4+ T-cell counts of ≥350 cells/μL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4+ T-cell counts of <250 cells/μL, AIDS, or death. Intervention and comparison arms had similar median CD4+ counts (517 and 534 cells/μL, respectively) and HIV RNA levels (4.6 and 4.7 log10 copies/μL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis.Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4+ T-cell counts of >350 cells/μL was safe and associated with clinical benefits.