Emma Hughes1, Norah Mwebaza2,3, Liusheng Huang4, Richard Kajubi2, Vy Nguyen4,5, Myaing M Nyunt6,7, Francis Orukan2, Moses W Mwima2, Sunil Parikh8, Francesca Aweeka4. 1. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA. 2. Infectious Disease Research Collaboration, Kampala, Uganda. 3. Department of Clinical Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda. 4. Department of Clinical Pharmacy, University of California, San Francisco, CA. 5. Currently, Dignity Health, Santa Cruz, CA. 6. Center for Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, MD. 7. Currently, Duke Global Health Institute, Durham, NC; and. 8. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT.
Abstract
BACKGROUND: The choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether-lumefantrine (AL) because no studies have isolated the impact of efavirenz for HIV-infected pregnant women. METHODS: A prospective clinical pharmacokinetic (PK) study compared HIV-infected, efavirenz-treated pregnant women with HIV-uninfected pregnant women in Tororo, Uganda. All women received the standard 6-dose AL treatment regimen for Plasmodium falciparum malaria with intensive PK samples collected over 21 days and 42-days of clinical follow-up. PK exposure parameters were calculated for artemether, its active metabolite dihydroartemisinin (DHA), and lumefantrine to determine the impact of efavirenz. RESULTS: Nine HIV-infected and 30 HIV-uninfected pregnant women completed intensive PK evaluations. Relative to controls, concomitant efavirenz therapy lowered the 8-hour artemether concentration by 76% (P = 0.013), DHA peak concentration by 46% (P = 0.033), and day 7 and 14 lumefantrine concentration by 61% and 81% (P = 0.046 and 0.023), respectively. In addition, there were nonsignificant reductions in DHA area under the concentration-time curve0-8hr (35%, P = 0.057) and lumefantrine area under the concentration-time curve0-∞ (34%, P = 0.063) with efavirenz therapy. CONCLUSIONS: Pregnant HIV-infected women receiving efavirenz-based antiretroviral therapy during malaria treatment with AL showed reduced exposure to both the artemisinin and lumefantrine. These data suggest that malaria and HIV coinfected pregnant women may require adjustments in AL dosage or treatment duration to achieve exposure comparable with HIV-uninfected pregnant women.
BACKGROUND: The choice of malaria treatment for HIV-infected pregnant women receiving efavirenz-based antiretroviral therapy must consider the potential impact of drug interactions on antimalarial exposure and clinical response. The aim of this study was to investigate the effects of efavirenz on artemether-lumefantrine (AL) because no studies have isolated the impact of efavirenz for HIV-infected pregnant women. METHODS: A prospective clinical pharmacokinetic (PK) study compared HIV-infected, efavirenz-treated pregnant women with HIV-uninfected pregnant women in Tororo, Uganda. All women received the standard 6-dose AL treatment regimen for Plasmodium falciparum malaria with intensive PK samples collected over 21 days and 42-days of clinical follow-up. PK exposure parameters were calculated for artemether, its active metabolite dihydroartemisinin (DHA), and lumefantrine to determine the impact of efavirenz. RESULTS: Nine HIV-infected and 30 HIV-uninfected pregnant women completed intensive PK evaluations. Relative to controls, concomitant efavirenz therapy lowered the 8-hour artemether concentration by 76% (P = 0.013), DHA peak concentration by 46% (P = 0.033), and day 7 and 14 lumefantrine concentration by 61% and 81% (P = 0.046 and 0.023), respectively. In addition, there were nonsignificant reductions in DHA area under the concentration-time curve0-8hr (35%, P = 0.057) and lumefantrine area under the concentration-time curve0-∞ (34%, P = 0.063) with efavirenz therapy. CONCLUSIONS: Pregnant HIV-infected women receiving efavirenz-based antiretroviral therapy during malaria treatment with AL showed reduced exposure to both the artemisinin and lumefantrine. These data suggest that malaria and HIV coinfected pregnant women may require adjustments in AL dosage or treatment duration to achieve exposure comparable with HIV-uninfected pregnant women.
Authors: Niresh Hariparsad; Srikanth C Nallani; Rucha S Sane; Donna J Buckley; Arthur R Buckley; Pankaj B Desai Journal: J Clin Pharmacol Date: 2004-11 Impact factor: 3.126
Authors: Kenneth F Ilett; Brian T Ethell; James L Maggs; Timothy M E Davis; Kevin T Batty; Brian Burchell; Tran Quang Binh; Le Thi Anh Thu; Nguyen Canh Hung; Munir Pirmohamed; B Kevin Park; Geoffrey Edwards Journal: Drug Metab Dispos Date: 2002-09 Impact factor: 3.922
Authors: Ritah F Mutagonda; Appolinary A R Kamuhabwa; Omary M S Minzi; Siriel N Massawe; Betty A Maganda; Eleni Aklillu Journal: Malar J Date: 2016-05-13 Impact factor: 2.979
Authors: Patrick G T Walker; Feiko O ter Kuile; Tini Garske; Clara Menendez; Azra C Ghani Journal: Lancet Glob Health Date: 2014-07-23 Impact factor: 26.763
Authors: Douglas Shaffer; Johnstone Kumwenda; Huichao Chen; Victor Akelo; Francis Angira; Josphat Kosgei; Ronald Tonui; Francis Ssali; Ashley McKhann; Evelyn Hogg; V Ann Stewart; Sean C Murphy; Robert Coombs; Robert Schooley Journal: J Acquir Immune Defic Syndr Date: 2022-02-01 Impact factor: 3.771