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The impact of the HIV drug efavirenz on the pharmacokinetic disposition of the antimalarial dihydroartemisinin-piperaquine in pregnant women residing in Tororo, Uganda
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2016 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction. Pregnant women are one of the major risk groups to get infected with malaria, which can infect the placenta. The parasite causes 10,000 maternal- and 200,000 infant deaths per year. HIV increases the risk of malaria infection. An effective intermittent preventive treatment during pregnancy (IPTp) is necessary to decrease the risk of placental malaria. There are concerns for the current IPTp, sulfadoxine-pyrimethamine, due to resistance.  Dihydroartemisinin-piperaquine (DP) is an effective and safe treatment, but more information is needed on how to optimize its dosing in this important population.

Aim. Evaluate the pharmacokinetic (PK) exposure of DP in HIV positive pregnant women (BC2) treated with efavirenz and HIV negative pregnant women (BC1).

Methods. 31 BC1 and 27 BC2-women received DP monthly or bimonthly as IPTp in Tororo, Uganda. BC2-women used efavirenz-based combination antiretroviral therapy (cART). Intensive PK sampling was done and the area under the concentration-time curve (AUC) was used when comparing DP exposure between BC1 and BC2 women.

Results.  A significant change in exposure was seen between BC1 and BC2 for both dihydroartemisinin (DHA) and piperaquine (PQ). The biggest difference was seen for PQ, where the exposure changed significantly when comparing BC2 monthly to BC1 monthly alone, or the BC1 bimonthly plus monthly. DHA only showed a significant change in exposure when comparing BC1 bimonthly plus monthly vs. BC2.

Conclusion. This study showed that there is a significant interaction between efavirenz and the anti-malarial combination dihydroartemisinin-piperaquine in pregnant women.

Place, publisher, year, edition, pages
2016.
Keyword [en]
Malaria
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-274328OAI: oai:DiVA.org:uu-274328DiVA: diva2:896272
Subject / course
Pharmacotherapy
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2016-01-21 Created: 2016-01-20 Last updated: 2016-01-21Bibliographically approved

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