Piperaquine and dolutegravir drug-drug interactions study in pregnant women

Chief Investigator: Prof Feiko ter Kuile (UK)

Principal investigator: Prof Karen Irma Barnes (South Africa)

Site Lead Investigator: Dr Clifford George Banda (Malawi)

Co-investigators: Prof Gary Maartens (South Africa), Prof Victor Mwapasa (Malawi), Dr Mwayiwawo Madanitsa (Malawi), Dr Eva Maria Hodel (UK)

Main objective

To understand the impact of standard antiretroviral therapy on the pharmacokinetic profile of piperaquine administered as dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in HIV-infected pregnant women in Malawi

Specific objectives

To compare the mean trough plasma concentrations and pharmacokinetic parameters of piperaquine, administered as standard 3-day treatment course of dihydroarteminin-piperaquine (DP), when co-administered with dolutegravir-based antiretroviral therapy (ART) regimen, and when co-administered with efavirenz-based ART regimen in pregnant women living with HIV in Malawi

To compare steady-state trough and pharmacokinetic parameters of dolutegravir when administered alone as dolutegravir based-ART, and when co-administered with DP for IPTp in pregnant women living with HIV in Malawi

Study summary

This is an open-label, non-randomised, fixed sequence, pharmacokinetic clinical trial, with intense blood sampling, in 22 pregnant women living with HIV, awaiting a switch from efavirenz- to dolutegravir-based ART according to the HIV treatment policy in Malawi (PACTR201910580840196). Pregnant women will be enrolled from 16 weeks of pregnancy and will contribute blood samples; i) while on DP and efavirenz-based ART (sequence 1), ii) when taking dolutegravir-based ART alone (sequence 2), and iii) when on DP and dolutegravir-based ART (sequence 3). The primary outcome will address the question on whether dolutegravir-based ART results in better exposure of the longer acting partner drug of DP, piperaquine, compared to efavirenz-based ART (sequence 1 samples versus those from sequence 3). Additionally, we will understand if coadministration of DP and dolutegravir-based ART impacts on drug exposure of dolutegravir (sequence 2 samples versus those from sequence 3).

Core research team

Chief Investigator: Prof Feiko ter Kuile

Principal Investigator: Prof Karen Barnes

Site Lead Investigator: Dr Clifford G Banda

Study Physician: Dr Dumisile Nkosi

Study Nurse: Mayamiko Kapulula

Study Nurse: Marumbo Chirwa

Data Entry Clerk: Sharon Muyaya Tostensen

Laboratory Technician: Steve Munharo

Study Driver: Mr Gilbert Chimungu


This study is part of the EDCTP2 programme supported by the European Union through a Career Development Fellowship (Grant number TMA2017CDF-1897).