Abstract
ObjectivesThe objectives of this study were to summarize antiretroviral drug concentrations in breast milk (BM) and exposure of breast-fed infants.MethodsThis 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.ResultsTwenty-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.ConclusionsTransfer 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.
Highlights
1.5 million HIV-positive women become pregnant each year.[1]
In contrast to well-resourced settings,[3,4,5] the WHO recommends exclusive breastfeeding in the developing world[6] despite breastfeeding accounting for a significant proportion of all mother-to-child transmissions of HIV.[5]
Fourteen were PK studies nested within PMTCTefficacy trials, 8 were observational PK studies and 2 were nested within early-phase clinical trials
Summary
1.5 million HIV-positive women become pregnant each year.[1]. The infection of some 400 000 infants annually led the WHO to encourage provision of efavirenz-based antiretroviral (ARV) therapy for pregnant HIV-positive women [prevention of mother-to-child transmission (PMTCT) options B and B+].2 Increasing numbers of women will receive ARVs throughout breastfeeding.In contrast to well-resourced settings,[3,4,5] the WHO recommends exclusive breastfeeding in the developing world (since formula feeding is associated with high infant mortality)[6] despite breastfeeding accounting for a significant proportion of all mother-to-child transmissions of HIV.[5]. 1.5 million HIV-positive women become pregnant each year.[1] The infection of some 400 000 infants annually led the WHO to encourage provision of efavirenz-based antiretroviral (ARV) therapy for pregnant HIV-positive women [prevention of mother-to-child transmission (PMTCT) options B and B+].2. Increasing numbers of women will receive ARVs throughout breastfeeding. In contrast to well-resourced settings,[3,4,5] the WHO recommends exclusive breastfeeding in the developing world (since formula feeding is associated with high infant mortality)[6] despite breastfeeding accounting for a significant proportion of all mother-to-child transmissions of HIV.[5] Infants of ARV recipients who acquire HIV via breast milk (BM) have high rates of drug resistance,[7,8] limiting treatment options and shortening life. Pharmacokinetic (PK) knowledge of ARV transfer to BM and breastfed infants is essential to understand the safety of prolonged
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