Metabolic and mitochondrial effects of antiretroviral drug exposure in pregnancy and postpartum: Implications for fetal and future health.

The George Washington University, School of Medicine, Department of Pediatrics, Washington, DC, USA. Electronic address: .
Seminars in Fetal and Neonatal Medicine (Impact Factor: 3.13). 11/2012; DOI: 10.1016/j.siny.2012.10.005
Source: PubMed

ABSTRACT Antiretroviral drugs (ARVs) are indispensable in the treatment and prevention of human immunodeficiency virus infection. Although their use before, during and after pregnancy is considered safe for mother and child, there are still lingering concerns about their long-term health consequences and the ramifications of their effects on lipid, glucose, intermediary and mitochondrial metabolism. This article reviews the known effects of ARVs on macromolecular and mitochondrial metabolism as well as the potential maternal, fetal, neonatal and adult health risks associated with abnormal energy metabolism during gestation. Recommendations about enhanced monitoring for these risks in affected populations are being provided.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of antiretroviral therapy for the prevention of mother-to-child transmission (PMTCT) of HIV is to achieve maximal suppression of maternal viral load with minimal maternal, fetal and infant toxicity during pregnancy, delivery and postpartum. In addition to the efficacy and toxicity of antiretroviral therapy, the consideration of HIV resistance in mothers and infected newborns further complicates therapeutic choices for PMTCT. This manuscript summarizes current approaches to PMTC in diverse international settings.
    Early human development 03/2014; 90S1:S13-S15. · 2.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antiretroviral therapy during pregnancy and breastfeeding is a proven strategy to help prevent mother to child transmission of HIV-1. Pharmacokinetic and physiologic changes during pregnancy affect absorption and distribution of effective antiretroviral therapy, and can result in lower therapeutic concentrations of drug although this may not impact mother to child transmission. Continued antiretroviral therapy postpartum can help to prevent transmission via breastfeeding in resource-limited settings, but more importantly, help preserve a mother’s health, which is critical to child survival. Current commercially available tools may be inadequate to assess the acquisition of drug resistant viral populations late in pregnancy, and therapeutic drug monitoring is not widely available. There is little longitudinal information on pharmacokinetics of antiretroviral agents during pregnancy and the postpartum period to help guide dosing and regimen choices, though very recently some data have become available and incorporated into new treatment guidelines. Consideration of fetal risks in the timing and choice of agents further narrows the spectrum of choices among the many antiretroviral agents now available. Postpartum challenges to adherence can further erode the effectiveness of antiretroviral therapy and potentially compound the issue of adequacy of dosing in late pregnancy. In resource rich settings, frequent monitoring of pregnant women for regimen tolerance, adherence and virologic success, with intensification of such monitoring postpartum, are strategies that may help preserve maternal health. Often women are intensively monitored during pregnancy, and subsequently less frequently at postpartum when more adherence issues can occur. These problems are compounded in resource-limited settings where continued drug availability may be the predominant challenge and choices of antiretroviral agents are narrow. Pregnancy represents one (and often more than one) time point in the continuum of a woman’s life, and it is important that in the course of treating mothers and infants to prevent vertical transmission of HIV, strategies that preserve future treatment options are critical to both maternal and child health.
    Current Treatment Options in Infectious Diseases. 06/2014; 6(2):183-195.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.
    International Journal of Environmental Research and Public Health 09/2014; 11(9):9897-9918. · 1.99 Impact Factor