Transplacental Transfer of Antiretroviral Drugs and Newborn Birth Weight in HIV-Infected Pregnant Women

Abstract

Although it is well known that antiretroviral drugs (ARVs) across the placenta in different extents, few data are available concerning the impact of the transplacental passage of ARVs on newborn outcome. The aim of this study is to evaluate the transplacental diffusion of ARVs and the clinical assessment of the newborn. Mother and cord lopinavir, nelfinavir, atazanavir and nevirapine plasma levels were determined by high-performance liquid chromatography. Newborn gestational age, weight, and Apgar score were recorded. Cord-to-mother ratio (C:M) was calculated to estimate the placental passage of ARVs. Preterm birth was defined as delivery at <37 weeks of gestation and low birth weight was defined as a birth weight of <2500g. Twenty-six HIV-infected pregnant women were enrolled. Nevirapine presented the highest C:M ratio (0.60 +/- 0.19), the C:M ratio of nelfinavir and atazanavir was 0.37 +/- 0.38 and 0.20 +/- 0.14, respectively. The lopinavir level in the cord was undetectable. The observed prevalence rate of neonatal low birth weight and preterm delivery was 19,2% (n = 5) and 15.4% (n = 4), respectively. A significant linear regression analysis was reported between the C:M ratio and newborn birth weight (p = 0.01). Although the role of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission is indisputable, these data indicate a pharmacological rationale to the association between birth weight and highly active antiretroviral therapy during pregnancy.

Placental Transfer of Maraviroc in an Ex Vivo Human Cotyledon Perfusion Model and Influence of ABC Transporter Expression

“…The concordance between the results obtained with the ex vivo placental perfusion model and the cord-to-maternal plasma (C:M) ratios has already been shown for various antiretroviral agents of the nucleoside reverse transcriptase inhibitor and protease inhibitor classes. Indeed, the results obtained with the perfused cotyledon model and suggesting a relatively high and low placental transfer for nucleotide reverse transcriptase inhibitors and protease inhibitors, respectively, are in accordance with those obtained in vivo using matched maternal and umbilical cord blood samples collected at the time of delivery (21,25,27,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). Nevertheless, despite the in vivo/ex vivo concordance reported in the literature, our results should be confirmed in vivo with calculation of ratios in paired maternal and cord blood samples.…”

Population Approach To Analyze the Pharmacokinetics of Free and Total Lopinavir in HIV-Infected Pregnant Women and Consequences for Dose Adjustment

“…However, this ratio is mostly dependent on delivery time, and maternal and fetal samples are rarely taken simultaneously. The values reported previously varied from Ͻ1% to 57% (8,(19)(20)(21)(22). In the present study, the estimated ratio was 11.6%, confirming that LPV placental transfer is low.…”

“…Placental transfer was estimated based on the exposure ratio between fetal and maternal LPV/r AUCs for 12 h. The placental transfer was estimated to be 11.6% (1.2% to 48.9%). This value is slightly lower than those suggested for the fetal-to-maternal concentration ratio at delivery (14 to 20%) (8,(19)(20)(21)(22)(23).…”

“…The LPV placental transfer is low and variable at 20% (coefficient of variation [CV], ϳ65%) (8,(19)(20)(21)(22)(23), but this transfer has only been reported as a ratio of concentrations, whatever the delay between drug administration and delivery. The LPV placental transfer variability can be explained by the differences of delays and may also be explained by the genetic polymorphisms of the placental transporters.…”

Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy

“…Previous studies have demonstrated placental transfer, with drug concentrations approaching 1 g/ml in maternal and cord blood ratios for certain nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) (15)(16)(17)32) with slightly lower ratios reported for non-NRTIs (18)(19)(20) and even lower ratios for the protease inhibitors (16,21). Studies analyzing placental transfer of TFV have reported variable results, with maternal and cord blood concentration ratios ranging from 0.82 to 6.0 (16,18).…”