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

Banda, Clifford G., Nkosi, Dumisile, Allen, Elizabeth, Workman, Lesley, Madanitsa, Mwayiwawo, Chirwa, Marumbo, Kapulula, Mayamiko, Muyaya, Sharon, Munharo, Steven, Wiesner, Lubbe, Phiri, Kamija S., Mwapasa, Victor, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617, Maartens, Gary and Barnes, Karen I. (2022) 'Effect of dihydroartemisinin/piperaquine for malaria intermittent preventive treatment on dolutegravir exposure in pregnant women living with HIV'. The Journal of Antimicrobial Chemotherapy, Vol 77, Issue 6, pp. 1733-1737.

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Abstract

Background
In sub-Saharan Africa, the burdens of malaria and HIV infections overlap. In settings with moderate-to-high malaria transmission intensity, pregnant women living with HIV (PLWH) require both ART and malaria intermittent preventive treatment (IPTp). Dihydroartemisinin/piperaquine has been identified as a promising alternative to sulfadoxine/pyrimethamine for IPTp. However, another antimalarial drug, artesunate/amodiaquine, similar to dihydroartemisinin/piperaquine, was previously shown to reduce dolutegravir exposure in non-pregnant adults.
Objectives
To investigate the effect of dihydroartemisinin/piperaquine on dolutegravir plasma exposure in pregnant women on dolutegravir-based ART.
Methods
We conducted an open-label, non-randomized, fixed-sequence, pharmacokinetic study in PLWH in Malawi. Dolutegravir concentrations were measured over a 24 h period, before and after the recommended 3 day treatment dose of dihydroartemisinin/piperaquine in 12 pregnant women in their second or third trimester. Non-compartmental analysis was performed, and geometric mean ratios (GMRs) and 90% 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 (AUC0–24) and Cmax by 30% (GMR 1.30; 90% CI 1.11–1.52) and 31% (GMR 1.31; 90% CI 1.13–1.51), respectively. The dolutegravir 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.
Conclusions
Dihydroartemisinin/piperaquine may be administered with dolutegravir-based ART in pregnant women as the modest increase in dolutegravir exposure, similar to pharmacokinetic parameter values published previously, ensures its efficacy without any clinically significant adverse events observed in this small study.

Item Type: Article
Subjects: WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine.
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WA Public Health > Health Problems of Special Population Groups > WA 309 Women's health
WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/jac/dkac081
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 08 Sep 2022 14:50
Last Modified: 08 Sep 2022 14:50
URI: https://archive.lstmed.ac.uk/id/eprint/20554

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