Browsing by Author "Walimbwa, Stephen I."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment
    (Antimicrobial agents and chemotherapy, 2020) Francis, Jose; Barnes, Karen I.; Workman, Lesley; Kredo, Tamara; Vestergaard, Lasse S.; Hoglund, Richard M.; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Walimbwa, Stephen I.; Chijioke-Nwauche, Ifeyinwa; Sutherland, Colin J.; Merry, Concepta; Dentia, Paolo
    Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavirritonavir- based antiretroviral therapy (ART), while it decreased by 47% with efavirenzbased ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations 200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.