Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study

Amanda H. Corbett; Dumbani Kayira; Nicole R. White; Nicole L. Davis; Athena P. Kourtis; Charles Chasela; Francis Martinson; Grace Phiri; Bonaface Musisi; Deborah Kamwendo; Michael G. Hudgens; Mina C. Hosseinipour; Julie A. E. Nelson; Sascha R. Ellington; Denise J. Jamieson; Charles van der Horst; Angela Kashuba; Breastfeeding, Antiretroviral and Nutrition (BAN) Study Team

doi:10.3851/IMP2739

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Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study

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Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study

Amanda H. Corbett, Dumbani Kayira, Nicole R. White, Nicole L. Davis, Athena P. Kourtis, Charles Chasela, Francis Martinson, Grace Phiri, Bonaface Musisi, Deborah Kamwendo, …

Antiviral therapy, Vol.19(6), pp.587-595

01/01/2014

DOI: 10.3851/IMP2739

PMCID: PMC4110187

PMID: 24464632

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https://www.ncbi.nlm.nih.gov/pmc/articles/4110187View

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Abstract

Background: An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral and Nutrition (BAN) Study was performed to describe drug exposure and antiviral response. Methods: Women using Combivir r (zidovudine [ZDV] + lamivudine [3TC]) + Aluvia (R) (lopinavir/ritonavir [LPV/ RTV]) were enrolled. Breast milk (BM), mother plasma (MP) and infant plasma (IP) samples were obtained over 6 h after observed dosing at 6, 12 or 24 weeks post-partum for drug concentrations and HIV RNA. Results: A total of 30 mother/infant pairs (10 each at 6, 12 and 24 weeks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, respectively, whereas LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24 weeks. The majority (98.3%) of BM concentrations were >HIVwt IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. Conclusions: ZDV and 3TC concentrated in BM whereas LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low antiretroviral concentrations in IP suggest prevention of transmission while breastfeeding may be due to antiretroviral effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early.

Infectious Diseases

Virology

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

Details

Title: Subtitle: Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study
Creators: Amanda H. Corbett - University of North Carolina at Chapel Hill
Dumbani Kayira - Univ N Carolina, UNC Project, Lilongwe, Malawi
Nicole R. White - Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA
Nicole L. Davis - Univ N Carolina, Gillings Sch Publ Hlth, Chapel Hill, NC USA
Athena P. Kourtis - Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA
Charles Chasela - Univ N Carolina, UNC Project, Lilongwe, Malawi
Francis Martinson - Univ N Carolina, UNC Project, Lilongwe, Malawi
Grace Phiri - Univ N Carolina, UNC Project, Lilongwe, Malawi
Bonaface Musisi - Univ N Carolina, UNC Project, Lilongwe, Malawi
Deborah Kamwendo - Univ N Carolina, UNC Project, Lilongwe, Malawi
Michael G. Hudgens - Univ N Carolina, Gillings Sch Publ Hlth, Chapel Hill, NC USA
Mina C. Hosseinipour - Univ N Carolina, UNC Project, Lilongwe, Malawi
Julie A. E. Nelson - University of North Carolina at Chapel Hill
Sascha R. Ellington - Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA
Denise J. Jamieson - Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA
Charles van der Horst - University of North Carolina at Chapel Hill
Angela Kashuba - Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA
Breastfeeding, Antiretroviral and Nutrition (BAN) Study Team
Resource Type: Journal article
Publication Details: Antiviral therapy, Vol.19(6), pp.587-595
DOI: 10.3851/IMP2739
PMID: 24464632
PMCID: PMC4110187
NLM abbreviation: Antivir Ther
ISSN: 1359-6535
eISSN: 2040-2058
Publisher: Int Medical Press Ltd
Number of pages: 9
Grant note: T32AI070114 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) P30AI050140; P30 AI050410; T32 AI070114 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
Language: English
Date published: 01/01/2014
Academic Unit: Obstetrics and Gynecology; VPMA - Administration
Record Identifier: 9984446281602771

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