We report a case of a vertically infected woman treated with darunavir/ritonavir plus a standard backbone before pregnancy. The analysis of darunavir/ritonavir concentrations in peripheral maternal plasma throughout pregnancy, as well as in umbilical cord blood at delivery, showed low levels of darunavir in the mother and limited transfer across the placenta.
[Show abstract][Hide abstract] ABSTRACT: HIV resides within anatomical 'sanctuary sites' where local drug exposure and viral dynamics may differ significantly from the systemic compartment. Widespread implementation of antiretroviral therapy has seen a significant decline in the incidence of mother-to-child transmission (MTCT) of HIV. In addition to suppression of maternal plasma/genital viral loads, antiretroviral agents that cross the placenta and achieve adequate concentrations in the fetal compartment may exert a greater prophylactic effect. Penetration of antiretrovirals in the fetal compartment is expressed by accumulation ratios derived from the measurement of drug concentrations in paired maternal plasma and umbilical cord samples. The nucleoside analogues and nevirapine accumulate extensively in cord blood and in the surrounding amniotic fluid, whereas the protease inhibitors (PIs) exhibit low-to-moderate placental accumulation. Early data suggest that high placental/neonatal concentrations are achieved with raltegravir, but to a lesser extent with etravirine and maraviroc (rank order of accumulation: raltegravir/nucleoside reverse transcriptase inhibitor [tenofovir > zidovudine/lamivudine/emtricitabine/stavudine/abacavir] > non-nucleoside reverse transcriptase inhibitor [nevirapine > etravirine] > PI > maraviroc/enfuvirtide). More comprehensive in vivo pharmacokinetic data are required to justify the potential use of these agents as safe and effective options during pregnancy.
[Show abstract][Hide abstract] ABSTRACT: Antiretroviral therapy (ART) in pregnant women represents a unique combination of therapy and prophylaxis of HIV infection. Until the global epidemic of HIV and the discovery of efficient prevention of perinatal transmission through ART, the world has not witnessed a pharmacologic intervention of such a scale during pregnancy and delivery. The use of ART in pregnancy creates unique challenges in delivering therapeutic agents, targeting the HIV virus in both the pregnant woman and her unborn child, throughout dramatic changes in their physiologic state. With an increased complexity of perinatal ART and the introduction of novel agents into clinical practice, a better understanding of the pharmacokinetics (PK) and pharmacodynamics of ARV drugs is crucial for the safe and most effective use of ARV drugs in women during pregnancy and infants in the first months of life. While PK studies are already difficult to perform during pregnancy, they are particularly challenging in women with HIV infection due to multiple social, economic and cultural constrains. In this paper we provide an overview of published studies of ART disposition during pregnancy, labor, breastfeeding and in the newborn infant after delivery.
Current Drug Metabolism 03/2012; 13(6):744-59. DOI:10.2174/138920012800840365 · 2.98 Impact Factor
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