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)
Pharmacokinetics and Safety Profile of Artesunate-Amodiaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 62 (7).
e00412-e00418.
Abstract
There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus-infected (HIV<sup>+</sup>) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared the area under the concentration-time curve from 0 to 28 days (AUC<sub>0-28</sub>) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV<sup>+</sup> adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria-uninfected adults (<i>n</i> = 6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort (<i>n</i> = 25/arm) received the full regimen. In step 1, there were no safety signals or significant differences in desethylamodiaquine AUC<sub>0-28</sub> among participants in the ritonavir-boosted lopinavir, nevirapine, and antiretroviral therapy-naive arms. In step 2, compared with those in the antiretroviral therapy-naive arm, participants in the ritonavir-boosted lopinavir arm had 51% lower desethylamodiaquine AUC<sub>0-28</sub>, with the following geometric means (95% confidence intervals [CIs]): 23,822 (17,458 to 32,506) versus 48,617 (40,787 to 57,950) ng · h/ml (<i>P</i> < 0.001). No significant differences in AUC<sub>0-28</sub> were observed between nevirapine and antiretroviral therapy-naive arms. Treatment-emergent transaminitis was higher in the nevirapine (20% [5/25]) than the antiretroviral therapy-naive (0.0% [0/25]) arm (risk difference, 20% [95% CI, 4.3 to 35.7]; <i>P</i> = 0.018). The ritonavir-boosted lopinavir antiretroviral regimen was associated with reduced desethylamodiaquine exposure, which may compromise artesunate-amodiaquine's efficacy. Coadministration of nevirapine and artesunate-amodiaquine may be associated with hepatoxicity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | amodiaquine, antiretroviral therapy, malaria, nevirapine, ritonavir-boosted lopinavir |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Jun 2018 10:04 |
| Last Modified: | 02 Feb 2024 03:09 |
| DOI: | 10.1128/AAC.00412-18 |
| Open Access URL: | http://dx.doi.org/10.1128/AAC.00412-18 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3022207 |
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