Browsing by Author "Boffito, Marta"

Now showing 1 - 5 of 5
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    Cardiac Conduction Safety during Coadministration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults
    (Chemotherapy research and practice, 2011) Byakika-Kibwika, Pauline; Lamorde, Mohammed; Lwabi, Peter; Nyakoojo, Wilson B.; Okaba-Kayom, Violet; Mayanja-Kizza, Harriet; Boffito, Marta; Katabira, Elly; Back, David; Khoo, Saye; Merry, Concepta
    We aimed to assess cardiac conduction safety of coadministration of the CYP3A4 inhibitor lopinavir/ritonavir (LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIV positive adults administered single-dose AL (80/400 mg) alone or with LPV/r (400/100 mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART naıve. All took single dose AL. No serious adverse events were observed. ECG parameters in milliseconds remained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P = .02) and 72 hours (424 versus 408; P = .004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-dose AL regimen with LPV/r should be investigated.
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    Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin
    (Journal of Antimicrobial Chemotherapy, 2011) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Okaba-Kayom, Violet; Ryan, Mairin; Coakley, Peter; Boffito, Marta; Namakula, Rhoda; Kalemeera, Francis; Colebunders, Robert; Back, David; Khoo, Saye; Merry, Concepta
    In resource-poor countries, HIV and tuberculosis (TB) co-infection results in significant morbidity and mortality. Co-treatment is recommended by the WHO;1 however, drug interactions are common between anti-TB regimens containing rifampicin and antiretroviral drugs. In these settings, rifampicin is a key drug for TB treatment because alternative rifamycins are more expensive and usually not available in public TB control programmes. Similarly, for HIV treatment, only a limited number of antiretroviral drugs are routinely used. The problems arising from limited drug options are compounded by the wide use of fixed-dose combination (FDC) formulations for both diseases. When these formulations are used, drug substitutions are not possible and dose adjustments are usually difficult.
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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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    Steady-state pharmacokinetics of lopinavir plus ritonavir when administered under different meal conditions in HIV-infected Ugandan adults
    (Journal of acquired immune deficiency syndromes, 2012) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Boffito, Marta; Nabukeera, Lillian; Mayito, Jonathan; Ogwal- Okeng, Jasper; Tjia, John; Back, David; Khoo, Saye; Ryan, Mairin; Merry, Concepta
    We investigated the effect of food on the steady-state pharmacokinetics of lopinavir and ritonavir in 12 Ugandan patients receiving lopinavir co-formulated with ritonavir (LPV/r) tablets using a cross-over design. Intensive pharmacokinetic sampling was performed seven days apart following LPV/r dosing under moderate fat, high fat and fasted meal conditions. Lopinavir and ritonavir concentrations were determined by liquid chromatography and tandem mass spectrometry. Compared to the fasted state, a high fat meal reduced lopinavir and ritonavir area under the curve (AUC) by 14% and 29%, respectively. With a moderate fat meal, AUC for both drugs was similar to the fasted state.
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    Suboptimal Nevirapine Steady-State Pharmacokinetics During Intrapartum Compared With Postpartum in HIV-1–Seropositive Ugandan Women
    (Journal of acquired immune deficiency syndromes, 2010) Lamorde, Mohammed; Byakika-Kibwika, Pauline; Okaba-Kayom, Violet; Flaherty, John P.; Boffito, Marta; Namakula, Rhoda; Ryan, Mairin; Nakabiito, Clemensia; Back, David J.; Khoo, Saye; Merry, Concepta; Scarsi, Kimberly K.
    Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa. Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNAwas performed within 2weeks of each visit. Nevirapine C12 above 3000 ng/mLwas classified as optimal based on the suggested value for therapeutic drug monitoring.