Banda, Clifford G, Dzinjalamala, Fraction, Mukaka, Mavuto, Mallewa, Jane, Maiden, Victor, Terlouw, Dianne J, Lalloo, David G 
ORCID: 0000-0001-7680-2200, Khoo, Saye H ORCID: 0000-0002-2769-0967 and Mwapasa, Victor
(2018)
Impact of Efavirenz-, Ritonavir-Boosted Lopinavir-, and Nevirapine-Based Antiretroviral Regimens on the Pharmacokinetics of Lumefantrine and Safety of Artemether-Lumefantrine in Plasmodium falciparum-Negative HIV-Infected Malawian Adults Stabilized on Antiretroviral Therapy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 62 (11).
e01162-e01118.
Abstract
There is conflicting evidence of the impact of commonly used antiretroviral therapies (ARTs) on the pharmacokinetics of lumefantrine and the safety profile of artemether-lumefantrine. We compared the area under the concentration-time curve from 0 h to 14 days (AUC0-14 days) of lumefantrine and the safety profile of artemether-lumefantrine in malaria-negative human immunodeficiency virus (HIV)-infected adults in two steps. In step 1, a half-dose adult course of artemether-lumefantrine was administered as a safety check in four groups (n = 6/group): (i) antiretroviral naive, (ii) nevirapine-based ART, (iii) efavirenz-based ART, and (iv) ritonavir-boosted lopinavir-based ART. In step 2, a standard-dose adult course of artemether-lumefantrine was administered to a different cohort in three groups (n = 10 to 15/group): (i) antiretroviral naive, (ii) efavirenz-based ART, and (iii) ritonavir-boosted lopinavir-based ART. In step 1, lumefantrine's AUC0-14 days was 53% (95% confidence interval [CI], 0.27 to 0.82) lower in the efavirenz-based ART group than in the ART-naive group and was 2.4 (95% CI, 1.58 to 3.62) and 2.9(95% CI, 1.75 to 4.72) times higher in the nevirapine- and ritonavir-boosted lopinavir groups, respectively. In step 2, lumefantrine's AUC0-14 days was 1.9 (95% CI, 1.26 to 3.00) times higher in the ritonavir-boosted lopinavir group and not significantly different between the efavirenz- and ART-naive groups (0.99 [95% CI, 0.63 to 1.57]). Frequent cases of hematological abnormalities (thrombocytopenia and neutropenia) were observed in the nevirapine group in step 1, leading to a recommendation from the data and safety monitoring board not to include a nevirapine group in step 2. Artemether-lumefantrine was well tolerated in the other groups. The therapeutic implications of these findings need to be evaluated among HIV-malaria-coinfected adults. (This study has been registered at the Pan African Clinical Trials Registry under numbers PACTR2010030001871293 and PACTR2010030001971409.).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | artemether-lumefantrine, antiretroviral therapy, malaria, antimalarial agents |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Jan 2019 10:55 |
| Last Modified: | 19 Jan 2023 01:07 |
| DOI: | 10.1128/AAC.01162-18 |
| Open Access URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC62010... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3030920 |
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