Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

<jats:p>Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need co-treatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artmether-lumefantrine or artesunate-amodiaquine given with 50mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artmether-lumefantrine or artesunate-amodiaquine and dolutegravir. The dolutegravir/artmether-lumefantrine interaction was evaluated in a two-way cross-over study and measured artemether, dihydroartemisinin, lumefantrine, desbutyl-lumefantrine over 264 hours. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, desethylamodiaquine over 624 hours. Non-compartmental analysis was performed, and geometric mean ratios and 90% confidence intervals generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, time to maximum concentration and area under the concentration-time curve (AUC) for artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine nor significantly alter AUC for artesunate, dihydroartemisinin, amodiaquine and desethylamodiaquine. Co-administration of dolutegravir with artmether-lumefantrine resulted in a 37% decrease in DTG trough concentrations. Co-administration of dolutegravir with artesunate-amodiaquine resulted in a decrease of approximately 42% and 24% in DTG trough concentrations and AUC respectively. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and dolutegravir exposure with artesunate-amodiaquine are unlikely to be of clinical significance as DTG trough concentrations were above dolutegravir target concentrations of 300ng/mL. Study drugs were well-tolerated with no serious adverse events. Standard doses of artemether-lumefantrine and artesunate-amodiaquine should be used in patients receiving dolutegravir.</jats:p>

Original publication

DOI

10.1128/aac.01310-18

Type

Journal article

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

12/11/2018