Dataset Information

Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding.

ABSTRACT: BACKGROUND:As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood, and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can uniquely quantify in utero transfer of maternal medications to infants. We measured plasma and hair antiretroviral levels in HIV-infected Ugandan mothers and their infants at delivery and during breastfeeding to assess transfer. METHODS:HIV-infected pregnant women were randomized to lopinavir/ritonavir- or efavirenz-based therapy in a larger trial (the Prevention of Malaria and HIV disease in Tororo, PROMOTE). At 0, 8, and 12 weeks postpartum, plasma antiretroviral levels were measured in 117 mother-infant pairs; hair levels were assayed at 12 weeks. Ratios and correlations of infant:maternal concentrations were calculated. RESULTS:By 12 weeks, 90.4% of mothers reported exclusive breastfeeding. Hair and plasma levels over time suggest moderate (47%) to extensive (87%) in utero transfer of lopinavir and ritonavir, respectively, but negligible transfer of either via breastfeeding. Moderate transfer of efavirenz occurs during pregnancy and breastfeeding (40% cumulative; 15% during breastfeeding). Despite differences in exposure, no infant seroconversions or correlations between infant hair/plasma antiretroviral levels and adverse effects were observed. CONCLUSIONS:Using a unique approach combining hair and plasma data, we found that different antiretrovirals have distinct kinetics of mother-to-infant transfer. Efavirenz transfers during both pregnancy and breastfeeding, whereas lopinavir and ritonavir transfer only in utero. Further study of the degree and timing of maternal-to-child transfer by antiretroviral will help optimize strategies that protect infants and minimize toxicities during periods of risk.

SUBMITTER: Gandhi M

PROVIDER: S-EPMC3800282 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding.

Gandhi Monica M Mwesigwa Julia J Mwesigwa Julia J Aweeka Francesca F Plenty Albert A Charlebois Edwin E Ruel Theodore D TD Huang Yong Y Clark Tamara T Ades Veronica V Natureeba Paul P Luwedde Flavia A FA Achan Jane J Kamya Moses R MR Havlir Diane V DV Cohan Deborah D

Journal of acquired immune deficiency syndromes (1999) 20130801 5

<h4>Background</h4>As efforts intensify to eliminate perinatal HIV transmission, understanding kinetics of maternal-to-child transfer of antiretrovirals during pregnancy and breastfeeding is critical. Antiretroviral levels in plasma, cord blood, and breastmilk reflect exposure over short intervals. Hair concentrations reflect cumulative exposure and can uniquely quantify in utero transfer of maternal medications to infants. We measured plasma and hair antiretroviral levels in HIV-infected Uganda ...[more]

PMID: 24135775

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Project description:Breast milk is considered the ideal infant nutrition, and medical organizations encourage breastfeeding worldwide. Moreover, breastfeeding is often perceived as a natural and spontaneous socio-biological process and one of the fundamental roles of new mothers. While breastfeeding is beneficial, little scientific consideration has been given to its potential psychological challenges. Here, we investigate the phenomenon of breastfeeding pain in mothers and its association with maternal and infant behavioral regulation. During the postpartum weeks, the mother-infant dyad can be considered one allostatic unit directed at infant regulation and development. We hypothesize that pain comprises an allostatic challenge for mothers and will thus impair the capacity for dyadic regulation. To test this, we recruited 71 mothers with varying levels of breastfeeding pain and videotaped them with their infants (2-35 weeks old) during spontaneous face-to-face interactions. We quantified the individual differences in dyadic regulation by behaviorally coding the second-by-second affective expressions for each mother and infant throughout their interactions. We tested the extent to which breastfeeding pain alters affect regulation during mother-infant interactions. We discovered that mothers with severe breastfeeding pain express less affective expressions and less infant-directed gaze during interactive moments of engagement and play than mothers with no or moderate pain. Moreover, infants of mothers experiencing pain during breastfeeding express less affective expressions and more mother-directed gaze while interacting with their mothers than infants of mothers who are not in pain. This demonstrates that the allostatic challenge of maternal pain interferes with the behavioral regulation of both mothers and infants. Since the mother-infant dyad is a codependent allostatic unit, the allostatic challenges of one partner can impact the dyad and thus potentially impact child development, bonding, and mother and infant well-being. The challenges of breastfeeding should be considered in addition to the nutritional advances.

Project description:The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines should be suitable to maintain values above the therapeutic pharmacokinetic targets in most infants. (This study has been registered at ClinicalTrials.gov under identifier NCT00640263.).

Dataset Information

Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding.

Publications

Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding.

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