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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration
Journal of Antimicrobial Chemotherapy, Volume 63, No. 1, Year 2009
Notification
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Description
Objectives: Nevirapine is widely used in the developing world for the prevention of mother-to-child transmission (PMTCT) of HIV. A single mutation in the HIV genome is sufficient to lead to significant nevirapine resistance. Persistence of low-level drug concentrations in body compartments can foster resistance formation. In this study, concentration-time courses of nevirapine after single-dose administration were analysed over an extended post-partum period. Patients and methods: Breast milk and plasma samples of 62 HIV-positive Ugandan mother-child pairs who had received single-dose nevirapine were collected at delivery and 1, 2 and 6 weeks post-partum. Nevirapine concentrations were quantified by LC/tandem-mass-spectrometry using a quantification limit of 15 ng/mL, and a population pharmacokinetic (PK) analysis was performed. Results: Concentration-time profiles in breast milk, maternal plasma and child plasma showed similar shapes. At week 1, median nevirapine concentrations were 164 ng/mL in maternal plasma, 114 ng/mL in breast milk and 183 ng/mL in child plasma. The population PK model predicted nevirapine concentrations > 10 ng/mL (IC50 for nevirapine) for 13 days in breast milk, 14 days in maternal plasma and 18 days in child plasma in 80% of the samples. Conclusions: Nevirapine concentrations were present for 2-3 weeks in the three compartments. The concentrations are probably sufficiently high to protect most breastfed children from HIV transmission during the first 2 weeks. The long presence of slowly decreasing levels of nevirapine is likely to induce resistance formation. Post-natal addition of antiretrovirals for 1 week only, as recommended in the current PMTCT guidelines, will not suffice to avoid nevirapine resistance formation. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Kunz, Andrea
Germany, Berlin
Charité – Universitätsmedizin Berlin
Frank, Monika
Germany, Halle
Martin-luther-universität Halle-wittenberg
Mugenyi, Kizito
Uganda, Fort Portal
Gtz Uganda
Kabasinguzi, Rose
Uganda, Fort Portal
Gtz Uganda
Weidenhammer, Astrid
Germany, Berlin
Charité – Universitätsmedizin Berlin
Kurowski, Michael
Germany, Berlin
Vivantes Auguste-viktoria-klinikum
Kloft, Charlotte
Germany, Halle
Martin-luther-universität Halle-wittenberg
Harms, Gundel
Germany, Berlin
Charité – Universitätsmedizin Berlin
Statistics
Citations: 45
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1093/jac/dkn441
ISSN:
03057453
e-ISSN:
14602091
Research Areas
Cancer
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study