Abstract

A monthly treatment course of dihydroartemisinin-piperaquine (DHA-PQ) effectively prevents malaria during pregnancy. However, a drug-drug interaction pharmacokinetic (PK) study found that pregnant HIV-infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population.Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal pharmacokinetic and QTc (25 women) data. Population PK and PK-QTc models for piperaquine were developed to consider the benefits (protective piperaquine coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective piperaquine coverage was defined as maintaining a concentration >10 ng/ml for >95% of the chemoprevention period.Piperaquine clearance was 4,540 L/day. With monthly DHA-PQ (2,880 mg piperaquine), <1% of women achieved defined protective piperaquine coverage. Weekly (960 mg piperaquine) or low dose daily (320 or 160 mg piperaquine) regimens, achieved protective piperaquine coverage for 34% and >96% of women respectively. All regimens were safe, with =2% of women predicted to have = 30 msec QTc increase.For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing.

View details for PubMedID 29272443