An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Abstract:

: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 lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based 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.

authors

Francis J,Barnes KI,Workman L,Kredo T,Vestergaard LS,Hoglund RM,Byakika-Kibwika P,Lamorde M,Walimbwa SI,Chijioke-Nwauche I,Sutherland CJ,Merry C,Scarsi KK,Nyagonde N,Lemnge MM,Khoo SH,Bygbjerg IC,Parikh S,Aweeka FT,

doi

10.1128/AAC.02394-19

subject

Has Abstract

pub_date

2020-04-21 00:00:00

issue

5

eissn

0066-4804

issn

1098-6596

pii

AAC.02394-19

journal_volume

64

pub_type

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