Abstract
Limited data are currently available on antiretroviral pharmacokinetics in breast milk (BM) and in breastfed infants’ blood. To explore these parameters in patients in Mali, we measured plasma antiretroviral levels in human immunodeficiency virus (HIV)–infected mothers and their breastfed infants over 6 months. We specifically analyzed the concentrations of efavirenz (EFV) and lopinavir (LPV) in the plasma of mothers living with HIV and their breastfed infants. Blood samples were collected at delivery and at month 1, 3, and 6 postpartum. EFV and LPV concentrations were measured by liquid chromatography-tandem mass spectrometry. HIV-1 RNA load was measured by Abbott M2000RT RealTime System at delivery and 6 months postpartum for mothers, and at 3 and 6 months postbirth for infants. The median duration of antiretroviral therapy at study inclusion was 57 months [interquartile range (IQR), 0–168 months]. The median EFV ratios of infant plasma/maternal plasma (MP) were 0.057 at month 1, 0.072 at month 3, and 0.048 at month 6. During the study period, the median BM/MP ratio of EFV was 1.16 (IQR, 0.96–20.62), which corresponds to a relative infant dose of 2.46% of the recommended weight-adjusted pediatric EFV dose at month 6. The apparent infant clearance of EFV was 0.146 l/h per kilogram at month 6. The LPV concentrations in the plasma of all infants were undetectable. No drug-related adverse reaction or toxicity was observed in any of the infants. The two women who presented a viral load of >50 copies/ml at month 6 had undetectable plasma drug concentrations at the same period. This study showed that breastfed infants received a low level of EFV but not LPV from their treated mothers.
Footnotes
- Received April 12, 2018.
- Accepted June 29, 2018.
This work was supported by University of Bamako Fund, Mali, as part of funding for A.A.O.’s effort, (Grant 2013-04); The Richard and Susan Kiphart Northwestern Global Health Research Fund (Grant 2015-01), and the Toulouse University Hospital agency (ARS) (Grant 2015-01). No potential conflicts of interest relevant to this article are reported.
Part of this work has been presented as follows: Oumar AA, Bagayoko-Maiga K, Seraissol P, Darin K, Fraissinet F, Bahachimi A, Sanogo A, Lavit M, Chatelut E, Sylla M, Dao S, Murphy R, Gandia P. Evaluation of efavirenz and lopinavir concentrations in plasma and prediction of uptake by nursed infants in Mali. 17th International Workshop on Clinical Pharmacology of HIV & Hepatitis; 2016 Jun 8–10; Washington DC.; Concentration d'Efavirenz et de lopinavir/r dans le lait maternel au Mali. Aboubacar Alassane Oumar, Bamako, Mali (Université des Sciences, des Techniques et des Technologies). 36th Interdisciplinary Meeting of Anti-Infectious Chemotherapy; 2016 Dec 12–13; Paris, France [Oral communication CO-021]; Oumar AA, Bagayoko-Maiga K, Darin K, Maiga M, Bahachimi A, Cere MC, Sanogo A, Chatelut E, Sylla M, Murphy R, Dao S, Gandia P. Evaluation du passage du Lopinavir/r dans le plasma et prédiction des quantités ingérées par le nourrisson allaité:étude chez la femme au Mali. 9th International Conference on AIDS and STIs in Africa; 2017 Dec 4–9; Abidjan, Ivory Coast [Oral communication S1164]; and Aboubacar Alassane Oumar, Kadiatou Bagayoko-Maiga, Mamoudou Maiga, Aliou Bahachimi, Marie-Christine CERE, Zoumana Diarra, Alou Sanogo, Etienne Chatelut, Mariam Sylla, Robert Leo Murphy, Sounkalo Dao, Peggy GANDIA. Evaluation du Passage de l'Efavirenz dans le Lait Maternel et Prédiction des Quantités Ingérées par Le Nourrisson Allaité: Etude Chez la Femme au Mali. AFRAVIH 2018: 9th Edition of the International Francophone Conference on HIV/HEPATITIS; 2018 Apr 4–7; Bordeaux, France [Oral communication S14-01].
- Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics