Browsing by Author "Else, Laura"

Now showing 1 - 5 of 5
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    Drug Interactions between Dolutegravir and Artemether- Lumefantrine or Artesunate-Amodiaquine
    (Antimicrobial agents and chemotherapy, 2018) Walimbwa, Stephen I.; Lamorde, Mohammed; Waitt, Catriona; Kaboggoza, Julian; Else, Laura; Byakika-Kibwika, Pauline; Amara, Alieu; Gini, Joshua; Winterberg, Markus; Chiong, Justin; Tarning, Joel; Khoob, Saye H.
    Across sub-Saharan Africa, patients with HIV on antiretrovirals often getmalaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemetherlumefantrine or artesunate-amodiaquine given with 50mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunateamodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264 h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624 h.
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    Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant
    (Journal of the International AIDS Society, 2014) Kimberly, Scarsi; Lamorde, Mohammed; Darin, Kristin; Dilly Penchala, Sujan; Else, Laura; Nakalema, Shadia; Byakika-Kibwika, Pauline; Khoo, Saye; Cohn, Susan; Merry, Concepta; Back, David
    Sub-dermal hormone implants, such as levonorgestrel (LNG), are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART) may be compromised given the potential for a cytochrome P450 3A-mediated drug-drug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP)- or efavirenz (EFV)-based ART.
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    Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study)
    (PLoS Med, 2019) Waitt, Catriona; Orrell, Catherine; Walimbwa, Stephen; Singh, Yashna; Kintu, Kenneth; Simmons, Bryony; Kaboggoza, Julian; Sihlangu, Mary; Coombs, Julie- Anne; Malaba, Thoko; Byamugisha, Josaphat; Amara, Alieu; Gini, Joshua; Else, Laura; Heiburg, Christie; Hodel, Eva Maria; Reynolds, Helen; Mehta, Ushma; Byakika-Kibwika, Pauline; Hill, Andrew; Myer, Landon; Lamorde, Mohammed; Khoo, Saye
    The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3). Methods and findings In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28–36 weeks of gestation, age 26 (19–42), weight 67kg (45–119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma.
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    Steady-State Pharmacokinetics of Rilpivirine under Different Meal Conditions in HIV-1-Infected Ugandan Adults
    (Journal of Antimicrobial Chemotherapy, 2015) Lamorde, Mohammed; Walimbwa, Stephen; Kibwika, Pauline Byakika; Katwere, Michael; Mukisa, Lillian; Sempa, Joseph B.; Else, Laura; Back, David J.; Khoo, Saye H.; Merry, Concepta
    To investigate the effect of food on the steady-state pharmacokinetics of rilpivirine when administered as a fixed-dose combination tablet containing tenofovir disoproxil fumarate, emtricitabine plus rilpivirine (TDF/FTC/RPV) in HIV-1-infected Ugandan patients.This was an open-label, three-period, longitudinal pharmacokinetic study with patients serving as their own controls. Fifteen consenting and virologically suppressed HIV-1-infected adults were switched from an efavirenz-based regimen to TDF/FTC/RPV for 56 days. Enrolled patients underwent 24 h blood sampling with TDF/FTC/RPV dosing in the fasted state (day 42), with a low-fat meal (11 g of fat/353 kcal, day 49) and with a moderate-fat meal (19 g of fat/589 kcal, day 56; reference). A viral load assessment was performed on day 56.Rilpivirine AUC0–24 was significantly decreased by 16% (geometric mean ratio, 90% CI: 0.84, 0.73–0.96) during administration in the fasted state when compared with AUC0–24 during administration with a moderate-fat meal. Similarly, rilpivirine C24 was significantly decreased by 21% (0.79, 0.65–0.97) in the fasted state compared with a moderate-fat meal. Pharmacokinetic parameters were unchanged during administration with a low-fat meal, except for C24, which was significantly increased by 15% (1.15, 1.01–1.31) when compared with the moderate-fat meal. Rilpivirine Cmax was similar under the three meal conditions. Virological suppression was unchanged at the end of the study.A food effect was observed for steady-state pharmacokinetic parameters of rilpivirine (AUC0–24 and C24) when TDF/FTC/RPV was administered in the fasted state compared with the moderate-fat meal. The TDF/FTC/RPV formulation can be administered with either a low-fat or moderate-fat meal.
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    Steady-state pharmacokinetics of rilpivirine under different meal conditions in HIV-1-infected Ugandan adults
    (Journal of Antimicrobial Chemotherapy, 2015) Lamorde, Mohammed; Walimbwa, Stephen; Byakika-Kibwika, Pauline; Katwere, Michael; Mukisa, Lillian; Sempa, Joseph B.; Else, Laura; Back, David J.; Khoo, Saye H.; Merry, Concepta
    Over 24 million people are living with HIV in sub-Saharan Africa, the region that also experiences the highest prevalence of food insecurity. ART is the cornerstone for management of HIV, but few treatment options are available in African countries. The WHO recommends that first-line antiretroviral regimens should include one of two NNRTIs, either efavirenz or nevirapine. Although these drugs are efficacious, some patients may experience treatment-limiting toxicities, drug resistance or drug interactions with these agents; hence the need for more treatment options.