12 research outputs found

    Characterization of Mutations in HIV Type 1 Isolates from 144 Cambodian Recently Infected Patients and Pregnant Women Naive to Antiretroviral Drugs

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    International audienceA baseline study has been conducted to determine the polymorphism of reverse transcriptase, protease, and envelope genes of HIV-1 isolates from 146 antiretroviral drug-naive Cambodian patients including 22 seroconverters and 124 pregnant women having been diagnosed HIV positive for less than 1 year. Amplification of at least one gene was successful for 144 isolates. All three genes were obtained for 136 isolates. Subtyping showed that CRF01_AE was predominant (130 cases). According to the ANRS September 2004 list, polymorphism substitutions (>50% versus the subtype B consensus) of CRF01_AE at drug resistance positions were observed only in protease: I13V (81%), E35D (87%), M36I (100%), R41K (96%), and H69K (100%). Two strains bore one major resistance mutation to PIs: M46I and N88D. Five other strains carried drug resistance mutations to RTIs: K70R (one strain), V75M (three strains), and K101E (one strain). Of the isolates 4.9% had drug resistance mutations to antiretroviral drugs

    Reverse Transcriptase Mutations in Cambodian CRF01_AE Isolates after Antiretroviral Prophylaxis against HIV Type 1 Perinatal Transmission

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    International audienceThis study explores amino acid changes of the reverse transcriptase (rt) of CRF01_AE isolates from pregnant women naive to antiretroviral drugs before and 2, 6, and 52 weeks after exposure to single dose nevirapine (sdNVP). Results based on 51 observations showed that the proportion of isolates with nonnucleoside reverse transcriptase inhibitor (NNRTI) RMs in the group treated with sdNVP (n = 35) increased from 0% pre-NVP to 22.9% at week 2 postpartum (pp) and 22.9% at week 6 pp. In the group treated with zidovudine + sdNVP (n = 16), the proportion with RM was 31.3% and 18.8% at weeks 2 and 6 pp, respectively. Only a few RMs were still detected at week 52 pp. No apparent subtype-specific treatment-related mutations were detected. NNRTI RM occurrence in CRF01_AE strains is similar to subtype A, D, and CRF02_AG strains after exposure to antiretroviral drugs for PMTCT

    Population Pharmacokinetics of Emtricitabine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Neonates▿

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    The objectives of this study were to evaluate emtricitabine (FTC) pharmacokinetics in pregnant women and their neonates and to determine the optimal prophylactic dose for neonates after birth to prevent mother-to-child transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200 mg) tablets—two tablets at the initiation of labor and one daily for 7 days postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry validated method and analyzed by a population approach. Model and mean estimates (interpatient variability) were a two-compartment model for mothers, with an absorption rate constant of 0.54 h−1 (61%), apparent elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters·h−1, and apparent central and peripheral volumes of 127 and 237 liters, respectively; an effect compartment linked to maternal circulation for cord blood and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life (30%). After the 400-mg FTC administration, the median population area under the concentration-time curve and the minimal and maximal plasma FTC concentrations in pregnant women were 14.3 mg·liter−1·h and 1.68 and 0.076 mg/liter, respectively. At delivery, median (range) predicted maternal and cord blood FTC concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg·liter−1. We concluded that the 400-mg FTC administration in pregnant women produces higher exposition than does the 200-mg administration in other adults, at steady state. FTC was shown to have good placental transfer (80%). Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after birth should produce neonatal concentrations comparable to the concentrations observed in adults

    Population Pharmacokinetics of Nevirapine in HIV-1-Infected Pregnant Women and Their Neonates ▿

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    The aim of the present study was to describe the nevirapine (NVP) pharmacokinetics (PK) in pregnant women and their neonates and to evaluate the transplacental drug transfer and administration scheme for the prevention of mother-to-child transmission. Thirty-eight HIV-1-infected pregnant women were administered one tablet of NVP (200 mg) and two tablets of tenofovir-emtricitabine (Truvada) at the initiation of labor. Children were given NVP syrup (2 mg/kg of body weight) as a single dose (sdNVP) on the first day of life. By pair, NVP concentrations were measured in 11 maternal, 1 cord blood, and 2 neonatal plasma samples and analyzed by a population approach. A one-compartment model was used for mothers and neonates; the absorption rate constants for mothers and neonates were 0.95 h−1 (intersubject variability, 111%) and 0.39 h−1, respectively; the apparent elimination clearances were 1.42 liter·h−1 (intersubject variability, 22%) and 0.035 liter·h−1, respectively; and apparent volumes of distribution were 87.3 liters (intersubject variability, 25%) and 5.65 liters, respectively. An effect compartment was linked to maternal circulation by mother-to-cord and cord-to-mother rate constants of 1.10 h−1 and 1.43 h−1, respectively. Placental transfer, expressed as the fetal-to-maternal area under the curve ratio, was 75%. Neonates had a very long half-lives (110 h) compared to adults. In the 38 mothers, the simulated median individual predicted time during which the NVP concentration remained above the half-maximal inhibitory concentration (IC50) was 13.2 days (range, 12 to 19.2 days). Thus, the administration of tenofovir-emtricitabine for at least 3 weeks after delivery should be considered to prevent the emergence of resistant viruses. The neonate must receive sdNVP immediately after birth when the infant is born less than 30 min after maternal drug intake to keep NVP concentrations above the IC50

    Une approche bioculturelle du premier aliment du nouveau-né. Le colostrum

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    International audienceThe "Colostrum" project, sponsored by the National Research Agency (ANR) from 2013 to 2016, is an interdisciplinary and international programme entirely dedicated to pre-milk newborn feeding. It concerns both the representations and practices around the donation of colostrum by the mother and its consumption by the child. It brought together 12 partners in 7 countries (Germany, Bolivia, Brazil, Burkina Faso, Cambodia, France, Morocco) spread over 4 continents, and the research itself includes four complementary components: anthropological, immunological, psychobiological, as well as an open science component for the restitution of results. The first part of the article displays the context of this research program, while the second part reveals the problem and the anthropological, immunological and psychobiological aspects of the program. The third and last part presents the first results, followed by general observations.Le projet « Colostrum » soutenu par l’Agence Nationale de la Recherche (ANR) de 2013 Ă  2016 est un programme interdisciplinaire et international entiĂšrement consacrĂ© Ă  l’alimentation prĂ©-lactĂ©e du nouveau-nĂ©. Il concerne aussi bien les reprĂ©sentations et pratiques autour du don de colostrum par la mĂšre que sa consommation par l’enfant. Il a rĂ©uni 12 partenaires dans 7 pays (Allemagne, Bolivie, BrĂ©sil, Burkina Faso, Cambodge, France, Maroc) rĂ©partis sur 4 continents.La recherche proprement dite comprend quatre volets complĂ©mentaires : anthropologique, immunologique, psychobiologique, ainsi qu’un volet open science pour la restitution des rĂ©sultats. La premiĂšre partie de l'article prĂ©sente le contexte dans lequel s’inscrit ce programme de recherche tandis que la deuxiĂšme dĂ©taille la problĂ©matique et les volets anthropologique, immunologique et psychobiologique du programme. La troisiĂšme et derniĂšre partie livre les premiers rĂ©sultats, puis conclue par des remarques de portĂ©e gĂ©nĂ©rale
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