Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV

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dc.contributor.advisorBarnes, Karen
dc.contributor.advisorMaartens Gary
dc.contributor.authorBanda, Clifford
dc.date.accessioned2023-06-23T06:59:20Z
dc.date.available2023-06-23T06:59:20Z
dc.date.issued2023
dc.date.updated2023-06-23T06:43:54Z
dc.description.abstractBackground: In sub-Saharan Africa, the disease burden of malaria and HIV infections overlap. In settings with moderate-to-high malaria transmission intensity, pregnant women living with HIV (PWLHIV) require both antiretroviral therapy and malaria intermittent preventive treatment (IPTp). Dihydroartemisinin-piperaquine has been identified as a promising alternative to sulfadoxine-pyrimethamine for malaria prevention in pregnancy. However, another antimalarial drug, artesunate-amodiaquine, similar to dihydroartemisininpiperaquine, was previously shown to reduce dolutegravir exposure in non-pregnant adults. Objective: To investigate the effect of dihydroartemisinin-piperaquine for IPTp on dolutegravir plasma exposure in pregnant women on dolutegravir-based antiretroviral therapy. Methods: We conducted an open-label, non-randomised, fixed sequence, pharmacokinetic study in PWLHIV in Malawi. Dolutegravir concentrations were measured over a 24-hour period, before and after the recommended three-day treatment dose of dihydroartemisininpiperaquine in 12 pregnant women in their 2nd or 3rd trimester. Non-compartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare dolutegravir pharmacokinetic parameters between the two treatment periods. Results: Co-administration of dihydroartemisinin-piperaquine and dolutegravir increased dolutegravir's overall exposure (AUC0-24hr) and maximum concentration (Cmax) by 30% (GMR,1.30; 90% CI, 1.11-1.52) and 31% (GMR, 1.31; 90% CI,1.13-1.51), respectively. Furthermore, dolutegravir's trough (C24) concentration increased by 42% (GMR,1.42; 90% CI,1.09-1.85). The combined treatments were well tolerated with no serious adverse events observed. Conclusion: Dihydroartemisinin-piperaquine may be administered as IPTp with dolutegravir-based antiretroviral therapy in pregnant women as the modest increase in dolutegravir exposure, similar to pharmacokinetic parameter values published previously, assures its efficacy without any clinically significant adverse events observed in this small studyen_US
dc.identifier.apacitationBanda, C. (2023). <i>Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV</i>. (). ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/37963en_ZA
dc.identifier.chicagocitationBanda, Clifford. <i>"Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV."</i> ., ,Faculty of Health Sciences ,Department of Medicine, 2023. http://hdl.handle.net/11427/37963en_ZA
dc.identifier.citationBanda, C. 2023. Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV. . ,Faculty of Health Sciences ,Department of Medicine. http://hdl.handle.net/11427/37963en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Banda, Clifford AB - Background: In sub-Saharan Africa, the disease burden of malaria and HIV infections overlap. In settings with moderate-to-high malaria transmission intensity, pregnant women living with HIV (PWLHIV) require both antiretroviral therapy and malaria intermittent preventive treatment (IPTp). Dihydroartemisinin-piperaquine has been identified as a promising alternative to sulfadoxine-pyrimethamine for malaria prevention in pregnancy. However, another antimalarial drug, artesunate-amodiaquine, similar to dihydroartemisininpiperaquine, was previously shown to reduce dolutegravir exposure in non-pregnant adults. Objective: To investigate the effect of dihydroartemisinin-piperaquine for IPTp on dolutegravir plasma exposure in pregnant women on dolutegravir-based antiretroviral therapy. Methods: We conducted an open-label, non-randomised, fixed sequence, pharmacokinetic study in PWLHIV in Malawi. Dolutegravir concentrations were measured over a 24-hour period, before and after the recommended three-day treatment dose of dihydroartemisininpiperaquine in 12 pregnant women in their 2nd or 3rd trimester. Non-compartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare dolutegravir pharmacokinetic parameters between the two treatment periods. Results: Co-administration of dihydroartemisinin-piperaquine and dolutegravir increased dolutegravir's overall exposure (AUC0-24hr) and maximum concentration (Cmax) by 30% (GMR,1.30; 90% CI, 1.11-1.52) and 31% (GMR, 1.31; 90% CI,1.13-1.51), respectively. Furthermore, dolutegravir's trough (C24) concentration increased by 42% (GMR,1.42; 90% CI,1.09-1.85). The combined treatments were well tolerated with no serious adverse events observed. Conclusion: Dihydroartemisinin-piperaquine may be administered as IPTp with dolutegravir-based antiretroviral therapy in pregnant women as the modest increase in dolutegravir exposure, similar to pharmacokinetic parameter values published previously, assures its efficacy without any clinically significant adverse events observed in this small study DA - 2023 DB - OpenUCT DP - University of Cape Town KW - Clinical Pharmacology LK - https://open.uct.ac.za PY - 2023 T1 - Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV TI - Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV UR - http://hdl.handle.net/11427/37963 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/37963
dc.identifier.vancouvercitationBanda C. Effect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV. []. ,Faculty of Health Sciences ,Department of Medicine, 2023 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/37963en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Medicineen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.subjectClinical Pharmacologyen_US
dc.titleEffect of dihydroartemisin-piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIVen_US
dc.typeThesis / Dissertationen_US
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