Publication: Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium falciparum uncomplicated malaria in adult patients on antiretroviral therapy in Malawi and Mozambique: An open label non-randomized interventional trial
Issued Date
2019-08-20
Resource Type
ISSN
14752875
Other identifier(s)
2-s2.0-85071221879
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Malaria Journal. Vol.18, No.1 (2019)
Suggested Citation
Esperança Sevene, Clifford G. Banda, Mavuto Mukaka, Sonia Maculuve, Salésio Macuacua, Anifa Vala, Mireia Piqueras, Linda Kalilani-Phiri, Jane Mallewa, Dianne J. Terlouw, Saye H. Khoo, David G. Lalloo, Victor Mwapasa Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium falciparum uncomplicated malaria in adult patients on antiretroviral therapy in Malawi and Mozambique: An open label non-randomized interventional trial. Malaria Journal. Vol.18, No.1 (2019). doi:10.1186/s12936-019-2909-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51030
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium falciparum uncomplicated malaria in adult patients on antiretroviral therapy in Malawi and Mozambique: An open label non-randomized interventional trial
Other Contributor(s)
Instituto de Salud Global de Barcelona
Universidade Eduardo Mondlane
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
University of Malawi College of Medicine
Liverpool School of Tropical Medicine
University of Liverpool
Mahidol University
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Centro de Investigação em Saúde de Manhiça (CISM)
Centre for Tropical Medicine
Universidade Eduardo Mondlane
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
University of Malawi College of Medicine
Liverpool School of Tropical Medicine
University of Liverpool
Mahidol University
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Centro de Investigação em Saúde de Manhiça (CISM)
Centre for Tropical Medicine
Abstract
© 2019 The Author(s). Background: HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Dihydroartemisinin-piperaquine (DPQ) is recommended for treatment of Plasmodium falciparum malaria, but its efficacy and safety has not been evaluated in HIV-infected individuals on ART, among whom drug-drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events were assessed in HIV-infected individuals on non-nucleoside reverse transcriptase inhibitor-based ART (efavirenz and nevirapine) with uncomplicated P. falciparum malaria treated with dihydroartemisinin-piperaquine. Methods: An open label single arm clinical trial was conducted in Malawi (Blantyre and Chikhwawa districts) and Mozambique (Manhiça district) involving patients aged 15-65 years with uncomplicated P. falciparum malaria who were on efavirenz-based or nevirapine-based ART. They received a directly-observed 3-day standard treatment of DPQ and were followed up until day 63 for malaria infection and adverse events. Day-42 PCR-corrected-ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat (ITT) population. Results: The study enrolled 160 and 61 patients on efavirenz and nevirapine-based ART, with a baseline geometric mean (95% CI) parasite density of 2681 (1964-3661) and 9819 (6606-14,593) parasites/μL, respectively. The day-42 PCR-corrected ACPR (95% CI) was 99.4% (95.6-99.9%) in the efavirenz group and 100% in the nevirapine group. Serious adverse events occurred in 5.0% (8/160) and 3.3% (2/61) of the participants in the efavirenz and nevirapine group, respectively, but none were definitively attributable to DPQ. Cases of prolonged QT interval (> 60 ms from baseline) occurred in 31.2% (48/154) and 13.3% (8/60) of the patients on the efavirenz and nevirapine ART groups, respectively. These were not clinically significant and resolved spontaneously over time. As this study was not designed to compare the efficacy and safety of DPQ in the two ART groups, no formal statistical comparisons were made between the two ART groups. Conclusions: DPQ was highly efficacious and safe for the treatment of malaria in HIV-infected patients concurrently taking efavirenz- or nevirapine-based ART, despite known pharmacokinetic interactions between dihydroartemisinin-piperaquine and efavirenz- or nevirapine-based ART regimens. Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013, https://pactr.samrc.ac.za/Search.aspx.