Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide
ABSTRACT The data on the use of tipranavir and enfuvirtide in pregnancy are very limited. We performed a pharmacokinetic profile in a pregnant woman with multidrug-resistant HIV-1 infection at 37 weeks gestation. Tipranavir levels were in the therapeutic range and the cord blood concentration at delivery was relatively high when compared with other protease inhibitors. No enfuvirtide was detected in the fetal compartment. Tipranavir and enfuvirtide were successfully used in pregnancy, but possible toxicities must be kept in mind.
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ABSTRACT: Prophylaxis and treatment with antiretroviral drugs and the use of elective caesarean section have resulted in a very low mother-to-child transmission of human immunodeficiency virus (HIV) during recent years. The availability of new antiretroviral drugs, updated general treatment guidelines and increasing knowledge of the importance of drug resistance, have necessitated regular revisions of the "Prophylaxis and treatment of HIV-1 infection in pregnancy" recommendations. For these reasons, The Swedish Reference Group for Antiviral Therapy (RAV) updated the 2007 recommendations at an expert meeting that took place on 25 March 2010. The most important revisions from the previous recommendations are: (1) it is recommended that treatment during pregnancy starts at the latest at gestational week 14-18; (2) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (3) lopinavir/r and atazanavir/r are equally recommended protease inhibitors; (4) if maternal HIV RNA is >50 copies/ml close to delivery, a planned caesarean section, intravenous zidovudine, oral nevirapine for the mother and post-exposure prophylaxis for the infant with 3 antiretroviral drugs are recommended; (5) for delivery at <34 gestational weeks, intravenous zidovudine and oral nevirapine for the mother and at 48-72 h for the infant is recommended, in addition to other prophylaxis; (6) intravenous zidovudine is not recommended when HIV RNA is <50 copies/ml and a caesarean section is performed; (7) it is recommended that prophylaxis for the infant is started within 4 h; (8) prophylactic zidovudine for the infant may be administered twice daily instead of 4 times a day, as was the case previously; and (9) the number of sampling occasions for the infant has been decreased.Scandinavian Journal of Infectious Diseases 03/2011; 43(6-7):411-23. DOI:10.3109/00365548.2011.567392 · 1.50 Impact Factor
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ABSTRACT: Antiretroviral therapy suppresses replication of HIV allowing restoration and/or preservation of the immune system. Providing combination antiretroviral therapy during pregnancy can treat maternal HIV infection and/or reduce perinatal HIV transmission. However, providing treatment to pregnant women is challenging due to physiological changes that can alter antiretroviral pharmacokinetics. Suboptimal drug exposure can result in HIV RNA rebound, the selection of resistant virus or an increased risk of HIV-1 transmission to the infant. Increased drug exposure can produce unwarranted maternal adverse effects and/or fetal toxicity. Subsequently, dose adjustments may be necessary during pregnancy to achieve comparable antiretroviral exposure to non-pregnant adults. For several antiretrovirals, systemic exposure is decreased during the last trimester of pregnancy. By 6-12 weeks postpartum, concentrations return to those prior to pregnancy. Also, the extent of antiretroviral placental transfer to the fetus and degree of antiretroviral excretion into breast milk varies within, and between, antiretroviral drug classes. It is necessary to consider the pharmacological characteristics of each antiretroviral when optimizing combination therapy during pregnancy to treat maternal HIV infection and prevent perinatal HIV transmission.Clinical Pharmacokinetics 10/2012; 51(10):639-59. DOI:10.1007/s40262-012-0002-0 · 5.05 Impact Factor
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ABSTRACT: Mother-to-child-transmission rates of HIV in the absence of any intervention range between 20 and 45%. However, the provision of antiretroviral drugs (ARVs) during pregnancy, delivery and breastfeeding can reduce HIV transmission to less than 2%. Physiological changes during pregnancy can influence ARV disposition. Associations between SNPs in genes coding for metabolizing enzymes, and/or transporters, and ARVs disposition are well described; however, relatively little is known about the influence of these SNPs on ARV pharmacokinetics during pregnancy and lactation as well as their effect on distribution into the fetal compartment and breast milk excretion. Differences in maternal, fetal and infant ARV exposure due to SNPs may affect the efficacy and safety of ARVs used to prevent mother-to-child-transmission. The aim of this review is to provide an update on the effect of pregnancy-induced changes on the pharmacokinetics of ARVs and highlight the potential role of pharmacogenetics.Pharmacogenomics 10/2012; 13(13):1501-22. DOI:10.2217/pgs.12.138 · 3.22 Impact Factor