Pharmacokinetics and safety profile of artesunate-amodiaquine co-administered with antiretroviral therapy in malaria uninfected HIV-positive Malawian adults

Banda, C; Dzinjalamala, F; Mukaka, M; Mallewa, J; Maiden, V; Terlouw, D; Lalloo, D; Khoo, S; Mwapasa, V

Journal article

Pharmacokinetics and safety profile of artesunate-amodiaquine co-administered with antiretroviral therapy in malaria uninfected HIV-positive Malawian adults

Abstract:: There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus infected (HIV+) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared area under the concentration-time curve from 0 to 28 days (AUC0-28 days) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV+ adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria uninfected adults (n=6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort (n=25/arm) received the full regimen. In step 1, there were no safety signals and significant differences in desethylamodiaquine AUC0-28 days among participants in the ritonavir-boosted lopinavir, nevirapine and antiretroviral therapy-naive arms. In step 2, compared with the antiretroviral therapy-naive arm, participants in the ritonavir-boosted lopinavir arm had 51% lower desethylamodiaquine AUC0-28 days, (geometric mean [95% CI]; 23,822 [17,458-32506] vs 48,617 [40,787-57,950] ng.hr/mL, p < 0.001). No significant differences in AUC0-28 days were observed between nevirapine and antiretroviral therapy-naïve arms. Treatment-emergent transaminitis was higher in the nevirapine (20% [5/25]) than the antiretroviral therapy naïve (0.0% [0/25]) arm (risk difference 20% [95% CI:4.3-35.7] p=0.018). Ritonavir-boosted lopinavir antiretroviral regimen was associated with reduced desethylamodiaquine exposure which may compromise artesunate-amodiaquine's efficacy. Co-administration of nevirapine and artesunate-amodiaquine may be associated with hepatoxicity.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Banda, C., Dzinjalamala, F., Mukaka, M., Mallewa, J., Maiden, V., Terlouw, D., Lalloo, D., Khoo, S., & Mwapasa, V. (2018). Pharmacokinetics and safety profile of artesunate-amodiaquine co-administered with antiretroviral therapy in malaria uninfected HIV-positive Malawian adults. Antimicrobial Agents and Chemotherapy, 62(7), e00412–18.

MLA Style

Banda, C, et al. “Pharmacokinetics and Safety Profile of Artesunate-Amodiaquine Co-Administered with Antiretroviral Therapy in Malaria Uninfected HIV-Positive Malawian Adults.” Antimicrobial Agents and Chemotherapy, vol. 62, no. 7, 2018, pp. e00412–18.

Chicago Style

Banda, C, F Dzinjalamala, M Mukaka, et al. 2018. “Pharmacokinetics and Safety Profile of Artesunate-Amodiaquine Co-Administered with Antiretroviral Therapy in Malaria Uninfected HIV-Positive Malawian Adults.” Antimicrobial Agents and Chemotherapy 62 (7): e00412–18.
Print