Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV
Issued Date
2022-12-01
Resource Type
ISSN
00664804
eISSN
10986596
Scopus ID
2-s2.0-85144479132
Pubmed ID
36374096
Journal Title
Antimicrobial Agents and Chemotherapy
Volume
66
Issue
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy Vol.66 No.12 (2022)
Suggested Citation
Banda C.G., Nkosi D., Allen E., Workman L., Madanitsa M., Chirwa M., Kapulula M., Muyaya S., Munharo S., Tarning J., Phiri K.S., Mwapasa V., ter Kuile F.O., Maartens G., Barnes K.I. Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV. Antimicrobial Agents and Chemotherapy Vol.66 No.12 (2022). doi:10.1128/aac.00584-22 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/85188
Title
Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV
Author's Affiliation
Kamuzu University of Health Sciences
Faculty of Tropical Medicine, Mahidol University
Malawi University of Science and Technology
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Liverpool School of Tropical Medicine
Nuffield Department of Medicine
University of Cape Town
Training and Research Unit of Excellence
Faculty of Tropical Medicine, Mahidol University
Malawi University of Science and Technology
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Liverpool School of Tropical Medicine
Nuffield Department of Medicine
University of Cape Town
Training and Research Unit of Excellence
Other Contributor(s)
Abstract
Dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, has been identified as a promising agent for intermittent preventive treatment of malaria in pregnancy. However, in pregnant women living with HIV (PLWH), efavirenz-based antiretroviral therapy (ART) significantly reduces the plasma exposure of piperaquine. In an open-label, nonrandomized, fixed-sequence, pharmacokinetic study, we compared piperaquine plasma concentrations in 13 pregnant women during a 3-day treatment course of dihydroartemisinin-piperaquine when coadministered with efavirenz-based versus dolutegravir-based ART in the second or third trimester of pregnancy. Piperaquine concentrations were measured over a 28-day period, while on efavirenz-based ART and after switching to dolutegravir-based ART. Noncompartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare piperaquine pharmacokinetic parameters between these two treatment periods. Compared with efavirenz-based ART, coadministration of dihydroartemisinin-piperaquine and dolutegravir-based ART resulted in a 57% higher overall piperaquine exposure (area under the concentration-time curve from 0 to 672 h [AUC0–672 h]) (GMR, 1.57; 90% CI, 1.28 to 1.93). Piperaquine’s day 7 concentrations were also 63% higher (GMR, 1.63; 90% CI, 1.29 to 2.11), while day 28 concentrations were nearly three times higher (GMR, 2.96; 90% CI, 2.25 to 4.07). However, the maximum piperaquine concentration (Cmax) remained similar (GMR, 1.09; 90% CI, 0.79 to 1.49). Dihydroartemisinin-piperaquine was well tolerated, with no medication-related serious adverse events observed in this small study. Compared with efavirenz-based ART, a known inducer of piperaquine metabolism, dolutegravir-based ART resulted in increased overall piperaquine exposure with pharmacokinetic parameter values that were similar to those published previously for pregnant and nonpregnant women. Our findings suggest that the efficacy of dihydroartemisinin-piperaquine will be retained in pregnant women on dolutegravir.