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Pharmacokinetic Optimization of Antiretroviral Therapy in Pregnancy

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Abstract

Antiretroviral therapy suppresses replication of HIV allowing restoration and/or preservation of the immune system. Providing combination antiretroviral therapy during pregnancy can treat maternal HIV infection and/or reduce perinatal HIV transmission. However, providing treatment to pregnant women is challenging due to physiological changes that can alter antiretroviral pharmacokinetics. Suboptimal drug exposure can result in HIV RNA rebound, the selection of resistant virus or an increased risk of HIV-1 transmission to the infant. Increased drug exposure can produce unwarranted maternal adverse effects and/or fetal toxicity. Subsequently, dose adjustments may be necessary during pregnancy to achieve comparable antiretroviral exposure to non-pregnant adults. For several antiretrovirals, systemic exposure is decreased during the last trimester of pregnancy. By 6–12 weeks postpartum, concentrations return to those prior to pregnancy. Also, the extent of antiretroviral placental transfer to the fetus and degree of antiretroviral excretion into breast milk varies within, and between, antiretroviral drug classes. It is necessary to consider the pharmacological characteristics of each antiretroviral when optimizing combination therapy during pregnancy to treat maternal HIV infection and prevent perinatal HIV transmission.

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Acknowledgments

Jennifer R. King has received salary support from grants IK23AI0074390-01 and U01-AI41089 from the National Institute of Allergy and Infectious Diseases. No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, 1530 3rd Ave. S., VH156, Birmingham, AL, 35294, USA

    Kajal Buckoreelall & Jennifer R. King

  2. Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    Tim R. Cressey

  3. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA

    Tim R. Cressey

  4. Institut de Recherche pour le Développement (IRD), UMI 174, Marseille, France

    Tim R. Cressey

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  1. Kajal Buckoreelall
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  2. Tim R. Cressey
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Correspondence to Jennifer R. King.

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Buckoreelall, K., Cressey, T.R. & King, J.R. Pharmacokinetic Optimization of Antiretroviral Therapy in Pregnancy. Clin Pharmacokinet 51, 639–659 (2012). https://doi.org/10.1007/s40262-012-0002-0

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