Tolerance of the newborn to antiretroviral drug exposure in utero

Abstract

Introduction: The prevention of mother-to-child HIV-1 transmission by antiretroviral drug treatment is remarkably effective. The risk of transmission to the child is now almost zero for women optimally treated during pregnancy. The rapid expansion of this prophylactic treatment has led the World Health Organization to aspire to the virtual elimination of mother-to-child transmission and pediatric AIDS over the next few years. In 2014, more than 900,000 women worldwide were treated with antiretroviral drugs during pregnancy. The issue of fetal and neonatal antiretroviral drug tolerance is therefore extremely important.

Areas covered: This review focuses on the possible impact of in utero exposure to antiretroviral drug on newborn health. To restrict analysis to this period is justified by the specificities of transplacental drug exposure and fetal vulnerability. Relevant data are available from trials and observational cohorts. The significance of various bio-markers detectable at birth is still unresolved, but merits a careful evaluation. Long-term assessment is associated with various logistical difficulties.

Expert opinion: The health of ‘exposed but not infected’ children poses no major problem in the immense majority of cases, but a series of biological, clinical and imaging-based warning signs have emerged indicating the need for careful attention to be paid to this issue. Some effects that are straightforward to manage in industrialized countries may have more severe consequences in countries in which access to effective healthcare is limited. Nucleoside/nucleotide analogs are potentially genotoxic to mitochondrial and nuclear DNA, and the principal question to be addressed concerns their potential long-term effects.

Keywords:

• antiretrovirals
• HIV
• pregnancy

Declaration of interest

The French ANRS-EPF cohort, the basis of this work on the tolerance of antiretroviral drugs, receives financial support from the Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) and Agence Nationale de Sécurité du Medicament (ANSM). We thank the families who agreed to participate in this cohort, and the investigators, for their strong commitment to this national collaborative research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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