201. Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz
- Author
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Moses R. Kamya, Prasanna Jagannathan, Paul Natureeba, Grant Dorsey, Radojka M. Savic, Philip J. Rosenthal, Liusheng Huang, Diane V. Havlir, Erika Wallender, Abel Kakuru, Mary K. Muhindo, Francesca T. Aweeka, Katarina Vučićević, and Mirium Nakalembe
- Subjects
0301 basic medicine ,Cyclopropanes ,and promotion of well-being ,HIV Infections ,Parasitemia ,Medical and Health Sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Dihydroartemisinin/piperaquine ,Pregnancy ,Immunology and Allergy ,030212 general & internal medicine ,Malaria, Falciparum ,intermittent preventive treatment during pregnancy ,education.field_of_study ,dihydroartemisinin-piperaquine ,Biological Sciences ,Artemisinins ,3. Good health ,Infectious Diseases ,Parasitic ,6.1 Pharmaceuticals ,Alkynes ,Combination ,Quinolines ,HIV/AIDS ,Drug Therapy, Combination ,Female ,Drug ,Infection ,Falciparum ,Adult ,medicine.medical_specialty ,Efavirenz ,Anti-HIV Agents ,030106 microbiology ,Population ,Microbiology ,Dose-Response Relationship ,03 medical and health sciences ,Antimalarials ,Young Adult ,Major Articles and Brief Reports ,Pharmacotherapy ,Rare Diseases ,Drug Therapy ,Clinical Research ,Piperaquine ,Internal medicine ,medicine ,Humans ,Dosing ,education ,3.3 Nutrition and chemoprevention ,Dose-Response Relationship, Drug ,business.industry ,Prevention ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,Prevention of disease and conditions ,HIV infection ,Malaria ,Benzoxazines ,Pregnancy Complications ,Good Health and Well Being ,chemistry ,Pregnancy Complications, Parasitic ,business ,drug-drug interaction - Abstract
BACKGROUND: 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 human immunodeficiency virus (HIV)–infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine (PQ) exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population. METHODS: Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal PK and corrected QT interval (QTc) (n = 25) data. Population PK and PK-QTc models for PQ were developed to consider the benefits (protective PQ coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective PQ coverage was defined as maintaining a concentration >10 ng/mL for >95% of the chemoprevention period. RESULTS: PQ clearance was 4540 L/day. With monthly DHA-PQ (2880 mg PQ), 96% of women, respectively. All regimens were safe, with ≤2% of women predicted to have ≥30 msec QTc increase. CONCLUSIONS: 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. CLINICAL TRIALS REGISTRATION: NCT02282293.
- Published
- 2017