title: Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies.
abstract: OBJECTIVE
  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 I(2) 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.
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Block A, The Waterhouse Buildings, 1-5 Brownlow Street, Liverpool L69 3GE, UK cwaitt@liv.ac.uk.
authors: Catriona John
authors: CJ
authors: Waitt
authors: Clinical Sciences Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
authors: Paul
authors: P
authors: Garner
authors: Department of Biostatistics, University of Liverpool, Faculty of Health and Life Sciences, 1st Floor Duncan Building, Daulby Street, Liverpool L69 3GA, UK Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, 8 West Derby Street, Liverpool L69 7BE, UK.
authors: Laura Jayne
authors: LJ
authors: Bonnett
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Block A, The Waterhouse Buildings, 1-5 Brownlow Street, Liverpool L69 3GE, UK.
authors: Saye Hock
authors: SH
authors: Khoo
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Block A, The Waterhouse Buildings, 1-5 Brownlow Street, Liverpool L69 3GE, UK.
authors: Laura Jayne
authors: LJ
authors: Else
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001942:Breast Feeding; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008895:Milk, Human / Q000737:chemistry*
chemical_list: D044966:Anti-Retroviral Agents
keywords: ARV; PK; mother-to-child transmission