Antiretroviral therapy during pregnancy and early neonatal life: consequences for HIV-exposed, uninfected children

Abstract

Women have emerged as the fastest growing human immunodeficiency virus (HIV) infected population worldwide, mainly because of the increasing occurrence of heterosexual transmission. Most infected women are of reproductive age and one of the greatest concerns for both women and their physicians is that more than 1,600 infants become infected with HIV each day. Almost all infections are a result of mother-to-child transmission of HIV. With the advent of combination antiretroviral therapies, transmission rates lower than 2% have been achieved in clinical studies. Antiretroviral compounds differ from most other new pharmaceutical agents in that they have become widely prescribed in pregnancy in the absence of proof of safety. We reviewed antiretroviral agents used in pregnant women infected with human immunodeficiency virus, mother-to-child transmission, and their consequences for infants.

Effects of antiretroviral agents during pregnancy on liver enzymes and amylase in HIV-exposed, uninfected newborn infants

“…It has been suggested that limited transfer of protease inhibitors may result from their high degree of plasma protein binding and their backwards transport through P-glycoprotein, largely expressed in the placenta [7]. Although there have been few studies analyzing adverse metabolic and biochemical effect of maternal ARV drugs on infant health [8], there have been no reports of the hepatic parameters of newborn infants during the immediate postnatal period [3].…”

“…Nucleoside reverse transcriptase inhibitors cross the placenta, with a maternalfetal drug transfer ratio close to 0.85 for zidovudine (ZDV), 1.0 for lamivudine (3TC), and minimal for protease inhibitors, including nelfinavir (NFV). Although this maternal-fetal transfer is beneficial regarding the prevention of the vertical transmission of HIV-1, antiretroviral agents (ARV) may expose the infant to the risk for adverse effects [2][3][4].…”

“…Despite a reasonable interest in this evaluation, there have been no studies evaluating prospectively the effects of maternal ARV use on the hepatic parameters and serum amylase of the neonates at birth [3]. Therefore, in the present study we assessed the effects of two different intrauterine exposures, i.e., prophylactic use of ZDV or triple antiretroviral treatment (ZDV + 3TC + NFV), on the transaminase, bilirubin and alkaline phosphatase levels and serum amylase levels of HIV-exposed uninfected neonates at birth.…”

Effect of Maternal Use of Antiretroviral Agents on Serum Insulin Levels of the Newborn Infant

“…The ZDV group consisted of 20 pregnant women who fulfilled the requirements for the prophylactic use of ZDV (CD4 Ͼ500 cells/mm 3 and viral load Ͻ1.000 copies/ml). The triple treatment group consisted of 25 pregnant women with a clinical and laboratory indication (CD4 Ͻ500 cells/mm 3 ) for triple antiretroviral treatment (ZDV ϩ lamivudine ϩ nelfinavir) according to the criteria established by the Perinatal HIV Guidelines Working Group Members regarding antiretroviral treatment of pregnant women.…”

“…Despite the association between the use of protease inhibitors and adverse glycemic metabolic effects, little evidence is available regarding unequivocal proof of the safety on uninfected infants born to HIV-infected mothers taking antiretroviral drugs (3). In the present series, we evaluated the effect of antiretroviral drugs during gestation on the glucose and insulin levels from the newborn infant.…”