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Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies

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Waitt, Catriona John, Garner, Paul ORCID: https://orcid.org/0000-0002-0607-6941, Bonnett, Laura Jayne, Khoo, Saye Hock and Else, Laura Jayne (2015) 'Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies'. The Journal of Antimicrobial Chemotherapy, Vol 70, Issue 7, pp. 1928-1941.

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Abstract

Objectives

The objectives of this study were to summarize antiretroviral drug concentrations in breast milk (BM) and exposure of breast-fed infants.

Methods

This was a systematic review of pharmacokinetic studies of HIV-positive women taking antiretrovirals that measured drugs in BM. The quality of pharmacokinetic and laboratory methods was assessed using pre-defined criteria. Pooled ratios and 95% CIs were calculated using the generalized inverse variance method and heterogeneity was estimated by the I2 statistic. PubMed Central, SCOPUS and LactMed databases were searched. No date or language restrictions were applied. Searches were conducted up to 10 November 2014. Clinical relevance was estimated by comparing ingested dose with the recommended therapeutic dose for each drug.

Results

Twenty-four studies were included. There was substantial variability in the clinical and laboratory methods used and in reported results. Relative to maternal plasma (MP), NRTIs accumulate in BM, with BM : MP ratios (95% CI estimates) from 0.89 to 1.21 (14 studies, 1159 paired BM and MP samples). NNRTI estimates were from 0.71 to 0.94 (17 studies, 965 paired samples) and PI estimates were from 0.17 to 0.21 (8 studies, 477 paired samples). Relative to the recommended paediatric doses, a breast-fed infant may ingest 8.4% (95% CI 1.9–15.0), 12.5% (95% CI 2.6–22.3) and 1.1% (95% CI 0–3.6) of lamivudine, nevirapine and efavirenz, respectively, via BM.

Conclusions

Transfer to untreated infants appears quantitatively important for some NRTIs and NNRTIs. The pharmacokinetic methods varied widely and we propose standards for the design, analysis and reporting of future pharmacokinetic studies of drug transfer during breastfeeding.

Item Type: Article
Subjects: QV Pharmacology > QV 38 Drug action.
WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine.
WS Pediatrics > Child Care. Nutrition. Physical Examination > WS 125 Breast feeding
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/jac/dkv080
Depositing User: Christianne Esparza
Date Deposited: 01 May 2015 13:12
Last Modified: 06 Feb 2018 13:09
URI: http://archive.lstmed.ac.uk/id/eprint/5124

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