PMID- 29986950
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20240501
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 366
IP  - 3
DP  - 2018 Sep
TI  - Efavirenz and Lopinavir Levels in HIV-Infected Women and Their Nursing Infants, 
      in Mali.
PG  - 479-484
LID - 10.1124/jpet.118.249938 [doi]
AB  - 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.
CI  - Copyright (c) 2018 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Oumar, Aboubacar Alassane
AU  - Oumar AA
AUID- ORCID: 0000-0002-3823-6962
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.) 
      aao@icermali.org.
FAU - Bagayoko-Maiga, Kadiatou
AU  - Bagayoko-Maiga K
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Bahachimi, Aliou
AU  - Bahachimi A
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Maiga, Mamoudou
AU  - Maiga M
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Cere, Marie-Christine
AU  - Cere MC
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Diarra, Zoumana
AU  - Diarra Z
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Chatelut, Etienne
AU  - Chatelut E
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Sylla, Mariam
AU  - Sylla M
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Murphy, Robert Leo
AU  - Murphy RL
AUID- ORCID: 0000-0002-9057-5144
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Dao, Sounkalo
AU  - Dao S
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
FAU - Gandia, Peggy
AU  - Gandia P
AUID- ORCID: 0000-0002-4385-7894
AD  - Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, 
      Purpan Hospital University, Toulouse, France (A.A.O., M.-C.C., P.G.); Institut 
      National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1037, 
      Pharmacology and Pharmacogenetics Laboratory, University Institute of Cancer 
      Oncopole, Toulouse, France (A.A.O., E.C.); HIV/Tuberculosis Research and Training 
      Center, University of Science, Techniques and Technologies, Bamako, Mali (A.A.O., 
      A.B., M.M., S.D.); Center for Global Health, Northwestern University, Chicago, 
      Illinois (M.M., R.L.M.); Department of Pediatric, University Hospital of Gabriel 
      Toure, Bamako, Mali (K.B.-M., M.S.); Referral Health Center V, Bamako, Mali 
      (Z.D.); and Institut National de la Recherche Agronomique Unite Mixte de 
      Recherche 1331-TOXALIM, Veterinary School of Toulouse, Toulouse, France (P.G.).
LA  - eng
GR  - D43 TW010350/TW/FIC NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180709
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 2494G1JF75 (Lopinavir)
RN  - JE6H2O27P8 (efavirenz)
MH  - Adolescent
MH  - Adult
MH  - Alkynes
MH  - Anti-HIV Agents/adverse effects/*blood/pharmacokinetics/therapeutic use
MH  - Benzoxazines/adverse effects/*blood/pharmacokinetics/therapeutic use
MH  - *Breast Feeding
MH  - Cyclopropanes
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - Humans
MH  - Infant
MH  - Lopinavir/adverse effects/*blood/pharmacokinetics/therapeutic use
MH  - Male
MH  - Mali
MH  - *Mothers
MH  - Safety
MH  - Tissue Distribution
MH  - Young Adult
PMC - PMC11056435
EDAT- 2018/07/11 06:00
MHDA- 2019/07/30 06:00
PMCR- 2018/09/01
CRDT- 2018/07/11 06:00
PHST- 2018/04/12 00:00 [received]
PHST- 2018/06/29 00:00 [accepted]
PHST- 2018/07/11 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/07/11 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - jpet.118.249938 [pii]
AID - JPET_249938 [pii]
AID - 10.1124/jpet.118.249938 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2018 Sep;366(3):479-484. doi: 10.1124/jpet.118.249938. Epub 
      2018 Jul 9.