An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment
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 in...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Society for Microbiology
2020
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| _version_ | 1797057421735100416 |
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| author | 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 Tarning, J Denti, P |
| author_facet | 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 Tarning, J Denti, P |
| author_sort | Francis, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:36:06Z |
| format | Journal article |
| id | oxford-uuid:1f18baa0-92fe-4c07-aff6-be5cebd6a961 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:36:06Z |
| publishDate | 2020 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:1f18baa0-92fe-4c07-aff6-be5cebd6a9612022-03-26T11:20:02ZAn individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1f18baa0-92fe-4c07-aff6-be5cebd6a961EnglishSymplectic ElementsAmerican Society for Microbiology2020Francis, JBarnes, KIWorkman, LKredo, TVestergaard, LSHoglund, RMByakika-Kibwika, PLamorde, MWalimbwa, SIChijioke-Nwauche, ISutherland, CJMerry, CScarsi, KKNyagonde, NLemnge, MMKhoo, SHBygbjerg, ICParikh, SAweeka, FTTarning, JDenti, PTreating 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. |
| spellingShingle | 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 Tarning, J Denti, P An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment |
| title | An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment |
| title_full | An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment |
| title_fullStr | An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment |
| title_full_unstemmed | An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment |
| title_short | An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment |
| title_sort | individual participant data population pharmacokinetic meta analysis of drug drug interactions between lumefantrine and commonly used antiretroviral treatment |
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