ABSTRACT
BACKGROUND: Physiological changes associated with pregnancy may alter antiretroviral plasma concentrations and might jeopardize prevention of mother-to-child HIV transmission. Lopinavir is one of the protease inhibitors more frequently prescribed during pregnancy in Europe. We described the free and total pharmacokinetics of lopinavir in HIV-infected pregnant and non-pregnant women, and evaluated whether significant alterations in its disposition and protein binding warrant systematic dosage adjustment. METHODS: Plasma samples were collected at first, second and third trimester of pregnancy, at delivery, in umbilical cord and postpartum. Lopinavir free and total plasma concentrations were measured by HPLC-MS/MS. Bayesian calculations were used to extrapolate total concentrations to trough (Cmin). RESULTS: A total of 42 HIV-positive pregnant women and 37 non-pregnant women on lopinavir/ritonavir were included in the study. Compared to postpartum and control values, total lopinavir Cmin was decreased moderately (31-39%) during pregnancy, and free Cmin minimally, showing significant alteration only at delivery (-35%). However, total and free Cmin remained in all patients above the target concentrations for wild-type virus of 1,000 ng/ml, and above the unbound IC50(WT) of 0.64-0.77 ng/ml of lopinavir, respectively. Lopinavir free fractions remained higher during pregnancy compared to postpartum and controls, and were influenced by α-1-acid-glycoprotein and albumin decrease. Free cord-to-mother ratio (0.43) was 2.7-fold higher than total cord-to-mother ratio (0.16), suggesting higher fetal exposure. CONCLUSIONS: The moderate decrease of total lopinavir concentrations during pregnancy is not associated with proportional decrease in free concentrations. Both reach a nadir at delivery, albeit not to an extent that would put treatment-naive women at risk of insufficient exposure to the free, pharmacologically active concentrations of lopinavir. No dosage adjustment is therefore needed during pregnancy as it is unlikely to further enhance treatment efficacy but could potentially increase the risk of maternal and fetal toxicity. Nonetheless, in case of viral resistance in treatment-experienced pregnant women, loss of virological control or questionable adherence, it is justified to consider lopinavir dosage adjustment based on total plasma concentration measurement.
Subject(s)
Anti-HIV Agents/pharmacokinetics , HIV Infections/drug therapy , Lopinavir/pharmacokinetics , Adult , Anti-HIV Agents/administration & dosage , Blood Proteins/metabolism , Delivery, Obstetric , Female , HIV Infections/blood , HIV Infections/transmission , Humans , Lopinavir/administration & dosage , Maternal-Fetal Exchange , Middle Aged , Orosomucoid/metabolism , Postpartum Period/blood , Pregnancy , Prospective Studies , Protein Binding , Serum Albumin/metabolism , Young AdultABSTRACT
OBJECTIVE: The purpose of this study was to investigate pregnant women's intentions for opting for caesarean section (CS), their experiences regarding previous births and their expectations for subsequent delivery. Our objectives were to identify medical and psychological predictors pertaining to the decision for CS on demand. DESIGN: The cross-sectional survey was conducted at two study centres over a three-month period including German speaking women at any time of pregnancy and consisted of an anonymous structured questionnaire. Logistic regression was computed to investigate the predictive value of medical variables, birth experience and birth anxiety on the demand for CS. RESULTS: Nineteen of 201 participants preferred to deliver by CS on demand and 15 felt uncertain about their decision. How the preceding delivery had been experienced was significantly better in the vaginal delivery (VD)-group (women not considering CS on demand) than in the CS-group (good experience in 81.7% and 52.0% respectively, p = 0.007). A negative previous birth experience and a preceding CS were predictors for the wish to deliver by CS. CONCLUSIONS: As negative birth experience predicts the wish for a CS, specific supportive care during first pregnancy could play a pivotal role in making this decision.
Subject(s)
Anxiety/psychology , Cesarean Section/psychology , Fear , Parity , Parturition/psychology , Patient Satisfaction , Pregnancy/psychology , Psychotherapy , Adult , Anxiety/diagnosis , Anxiety/therapy , Cross-Sectional Studies , Culture , Decision Making , Female , Humans , Intention , Labor Pain/psychology , Obstetric Labor Complications/psychology , Psychometrics , Surveys and Questionnaires , Switzerland , Young AdultABSTRACT
AIMS: To assess pregnant women's awareness of and attitudes towards cesarean section (CS) on demand, as well as to identify specific target groups by focusing on differences dependant on the participants' background, parity and intended mode of delivery. METHODS: The study was conducted at two centers during three months. German-speaking pregnant women were invited to answer an anonymous, structured questionnaire. We compared urban vs. rural, nulliparous vs. parous and women opting for a CS vs. denying this wish, with regard to awareness and attitudes towards CS on demand. RESULTS: Ninety-two percent of the 201 participants were aware of the possibility to deliver by CS on demand. Their sources of information were mostly print media reports, television, or friends. Pain avoidance and missing the birth experience were the main reasons for and against CS on demand, respectively. For women opting for CS on demand, traumatically-experienced previous birth and the child's well-being were other important reasons for a CS. CONCLUSIONS: Because negative birth experience appears to be decisive for pregnant women's attitude towards CS on demand and their perception of CS seems to be partly based on misconceptions, antenatal counseling should focus on these aspects.
