Stavudine Concentrations in Women Receiving Postpartum Antiretroviral Treatment and Their Breastfeeding Infants

Abstract

First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/ml in plasma, 20 ng/ml in breast milk). Median (interquartile range) d4T concentrations were 86 (36–191) ng/ml in maternal plasma, 151 (48–259) ng/ml in whole milk, 190 (58–296) ng/ml in skim milk, and <5 (<5-<5) ng/ml in infant plasma. While d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant.

Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

“…Another finding in this study was the association of increased GAG2 diversity among infants whose mothers did not have a history of ARV drug use (other than sdNVP for PMTCT). Maternally-administered ARV drugs are known to be transferred to infants in utero and during breastfeeding [39] – [41] and can induce ARV drug resistance in infants [42] , [43] . In settings where women are receiving ARV drugs while breastfeeding (e.g., ART for their own infection or a triple drug regimen for prevention of post-natal HIV transmission), this might result in a decrease in the diversity of the infant's virus (i.e., genetic bottlenecking), similar to that observed when children are maintained on non-suppressive ART [5] .…”

Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

“…Child mortality was still significant and similar to other contemporary cohorts in Malawi [18,19]. The high rate of gastroenteritis associated to early weaning [20,21] has certainly played a role, further supporting the prolonged period of breastfeeding of the new guidelines.…”

“…Interestingly, in our study the only predictor of child mortality was maternal baseline CD4+ count < 350/mm 3 (this was not true for HIV-free survival, due to the significant proportion of transmitting women with high CD4+ count). In a previous study conducted in Malawi in the pre-ART era [19], infant birth weight represented the most important factor associated to mortality up to 2 years. We cannot exclude the role of birth weight in our study since it was of borderline significance in univariate analysis and because this parameter was not available for all the children.…”

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

“…23,32 Two studies have measured tenofovir in BM. In one, tenofovir was measurable in the BM of only 4 out of 25 women sampled and neither study reported corresponding MP or IP concentrations.…”

“…Three studies report stavudine BM : MP ratios of >1 23 , 31 , 32 with a pooled estimate of 1.21 (1.07–1.36), which is significantly >1; however, infant concentrations approached the lower limit of quantification with a median value of zero. 23 , 32 Two studies have measured tenofovir in BM. In one, tenofovir was measurable in the BM of only 4 out of 25 women sampled and neither study reported corresponding MP or IP concentrations.…”