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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 MD, MPH*; Mwesigwa, Julia MBCHB, MSc; Aweeka, Francesca PharmD; Plenty, Albert BA, MS§; Charlebois, Edwin PhD, MPH*,§; Ruel, Theodore D. MD; Huang, Yong PhD; Clark, Tamara MS*; Ades, Veronica MD, MPH; Natureeba, Paul MBCHB; Luwedde, Flavia A. MBCHB; Achan, Jane MD, MMED; Kamya, Moses R. MBCHB, MMED, MPH, PhD; Havlir, Diane V. MD*; Cohan, Deborah MD, MPH#; for the Prevention of Malaria and HIV disease in Tororo (PROMOTE) study

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 August 2013 - Volume 63 - Issue 5 - p 578–584
doi: 10.1097/QAI.0b013e31829c48ad
Clinical Science

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.

*Department of Medicine, University of California, San Francisco, San Francisco, CA;

Infectious Diseases Research Collaboration, Makerere University College of Health Sciences-University of California, San Francisco, Kampala, Uganda;

Department of Clinical Pharmacy;

§Center for AIDS Prevention Studies;

Departments of Pediatrics;

Bioengineering and Therapeutic Sciences; and

#Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA.

Correspondence to: Monica Gandhi, MD, MPH, Division of HIV/AIDS, Department of Medicine, University of California, San Francisco, 405 Irving St, 2nd floor, San Francisco, CA 94122 (e-mail: monica.gandhi@ucsf.edu).

The authors have no conflicts of interest to disclose.

Presented at the 4th International Workshop on HIV Pediatrics, July 20–21, 2012, Washington, DC (oral abstract O-14) and XIX International AIDS Conference, July 22–27, 2012, Washington, DC (abstract TUPE057).

Supported by the National Institute of Child Health and Human Development/National Institutes of Health (NIH) (P01 HD059454, D.V.H.). Additional funding is provided by the National Institute of Allergy and Infectious Diseases/NIH (RO1 AI098472, M.G.). The plasma level analysis was supported by University of California, San Francisco Center for AIDS Research (P3O AI022763) Pharmacology Core. Lopinavir/ritonavir for study participants was provided by Abbvie (formerly Abbott Laboratories).

Received March 01, 2013

Accepted May 13, 2013

© 2013 by Lippincott Williams & Wilkins