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

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.

Expert consensus for managing pregnant women and neonates born to mothers with suspected or confirmed novel coronavirus (COVID‐19) infection

“…Lopinavir/ritonavir (200 mg/50 mg, per capsule) two capsules, twice per day. Lopinavir/ritonavir has been used in the treatment of pregnancy with HIV and the data show no significant teratogenicity; the concentration in breast milk is very low, and no lopinavir/ritonavir is detected in breastfed infants …”

Transmission of CMV, HTLV-1, and HIV through breastmilk

“…The peak concentrations of ART in breast milk lag behind those for plasma, and the elimination phase may be prolonged; such kinetics are seen for the nucleoside reverse transcriptase inhibitors (NRTIs) 100 . Exclusively breastfed infants receive up to 10% of the weight--adjusted infant dose of NRTIs and non--NRTIs (NNRTIs) whereas protease inhibitors have little transfer to the infant 101 . Genetic differences, such as CYP2B6 polymorphisms in the case of efavirenz, result in higher infant drug exposure 102 .…”

Efavirenz and Lopinavir Levels in HIV-Infected Women and Their Nursing Infants, in Mali

“…The extent of antiretroviral passage from maternal plasma (MP) to breast milk (BM) and then to infant plasma (IP) varies considerably by antiretroviral drug class and individual agent. A recent systematic review of 24 studies (Waitt et al, 2015) that evaluated antiretroviral pharmacokinetics (PK) in breastfeeding, HIV-infected women reported a pooled point estimate for BM-to-MP ratio of 0.89 to 1.21 for the nucleoside reverse transcriptase inhibitors (14 studies, 1159 paired samples), 0.71 to 0.94 for the non-nucleoside reverse transcriptase inhibitors (17 studies, 965 paired samples), and 0.17 to 0.21 for the protease inhibitors (eight studies, 477 paired samples). In addition, some studies have evaluated efavirenz (EFV) concentrations in the BM of lactating HIV-infected mothers (Schneider et al, 2008;Olagunju et al, 2015;Palombi et al, 2016).…”