Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 63, Issue 5, Pages 578-584Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31829c48ad
Keywords
HIV; lopinavir/ritonavir; efavirenz; maternal-to-child transfer; hair/plasma; concentrations; perinatal transmission
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Funding
- NIAID NIH HHS [UM1 AI069496, R01 AI098472, P30 AI027763, R37 AI098472, P3O AI022763] Funding Source: Medline
- NICHD NIH HHS [K23 HD060459, P01 HD059454] Funding Source: Medline
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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.
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