TUPE057 - Poster Exhibition
Lopinavir and efavirenz concentrations in paired hair samples as a marker of cumulative exposure among postpartum women and breastfeeding infants in Tororo, Uganda
J. Mwesigwa1, D. Cohan2, A. Plenty3, E. Charlebois3, T. Ruel4, V. Ades2, T.D. Clark5, P. Natureeba1, M.R. Kamya6, J. Achan7, D.V. Havlir5, M. Gandhi5, Prevention of Malaria and HIV Disease in Tororo (PROMOTE) Study
1Makerere University-UCSF Research Collaboration, Kampala, Uganda, 2University of California at San Francisco, Obstretrics, Gynecology and Reproductive Sciences, San Francisco, United States, 3University of California at San Francisco, Center for AIDS Prevention Studies, San Francisco, United States, 4University of California at San Francisco, Pediatrics, San Francisco, United States, 5University of California at San Francisco, Medicine, San Francisco, United States, 6Makerere University, Medicine, Kampala, Uganda, 7Makerere University, Pediatrics, Kampala, Uganda
Background: As increasing numbers of African women receive antiretrovirals (ARVs) during breastfeeding, understanding kinetics of ARV transfer to infants through breast milk is critical. ARV levels in plasma or breast milk reflect exposure over short time intervals. By contrast, ARV levels in hair samples measure cumulative exposure over weeks to months and are strongly associated with virologic suppression and adverse effects in treated individuals. We measured hair concentrations of ARVs in HIV-infected mothers receiving ARVs and their infants after 12 weeks of breastfeeding in Tororo, Uganda
Methods: As part of the Prevention of Malaria and HIV disease in Tororo (PROMOTE) study, HIV-infected pregnant women were randomized to lopinavir/ritonavir-based or efavirenz-based therapy. At 12 weeks postpartum, ~20 strands of hair were collected from mothers and infants, ARVs extracted, and concentrations measured using liquid chromatography/tandem mass spectrometry. The mean ratios of infant:maternal concentrations were calculated for each drug and Spearman correlations between infant adverse events and hair ARV concentrations were examined.
Results: As of September 2011, 268 pregnant women had been enrolled and 259 infants born. All infants were HIV-uninfected at 12 weeks. We collected small hair samples from 45 mother-infant pairs on lopinavir/ritonavir and 64 on efavirenz at 12 weeks and found mean infant/maternal hair concentration ratios of 0.867 for lopinavir and 0.396 for efavirenz (Table). There was no significant correlation between infant hair levels of ARVs and adverse effects.
Conclusions: We report for the first time the kinetics of ARV transfer from mother to infant during breastfeeding by assessing levels of ARVs in paired hair samples. Cumulative infant exposure to lopinavir during breastfeeding was much higher than exposure to efavirenz as assessed by hair concentrations (87% transfer via breastfeeding versus 40%) with equal rates of protection from HIV acquisition. Further work to correlate cumulative infant exposure to ARVs via breastfeeding and toxicities is needed.
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