Antiretroviral use during pregnancy for treatment or prophylaxis
ABSTRACT INTRODUCTION: Antiretrovirals are recommended for all pregnant women either for treatment of HIV-1 infection or for prevention of mother-to-child transmission. Distinguishing between HIV-1-infected pregnant women who meet treatment criteria and those who do not (who use antiretrovirals during pregnancy for prophylaxis) is accomplished by assessing the HIV-1 disease stage and has important implications regarding when antiretroviral drugs are initiated during pregnancy, what drugs are used and antiretroviral use after delivery. AREAS COVERED: This review addresses antiretroviral use by HIV-1-infected women during pregnancy. Specifically, the review focuses on antiretroviral therapy for HIV-1-infected pregnant women who meet criteria for treatment and antiretroviral prophylaxis for HIV-1-infected pregnant women (to prevent mother-to-child transmission of HIV-1). The review primarily addresses antiretroviral use in resource-rich settings, but use in resource-poor settings is briefly addressed. EXPERT OPINION: Antiretrovirals represent only one component of the overall management of HIV-1 infected pregnant women and, therefore, cannot be viewed in isolation from other components of optimal care for HIV-1-infected women and from other efficacious interventions to prevent mother-to-child transmission of HIV-1. Antiretrovirals can be used safely and effectively during pregnancy. We concur with current guidelines regarding the threshold that differentiates which women need antiretroviral therapy for HIV-1 infection for their own health versus those who need prophylaxis to prevent transmission of HIV-1 infection to their child. We thus recommend that lifelong antiretroviral therapy be initiated in patients with an AIDS-defining illness, a CD4 count < 350 cells/mm(3) or other co-morbid conditions such as acute opportunistic infections, HIV-1-associated nephropathy or hepatitis B co-infection. Irrespective of whether or not antiretrovirals are used during pregnancy, or whether antiretrovirals during pregnancy are used for treatment or prophylaxis, all infants of HIV-1-infected women should receive antiretroviral post-exposure prophylaxis.
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ABSTRACT: Lersivirine is a second-generation nonnucleoside reverse transcriptase inhibitor undergoing clinical development for the treatment of human immunodeficiency virus-1. An embryo-fetal development study was performed to evaluate the potential for maternal and developmental toxicity of lersivirine. Pregnant New Zealand White rabbits were administered 0, 100, 250, and 500 mg/kg lersivirine by oral gavage once daily on gestation days (GDs) 7 to 19, followed by cesarean section on GD 29 and fetal evaluation. Maternal toxicity was noted at all dose levels (decreased food consumption and body weight gain), with fetal toxicity at 500 mg/kg (decreased fetal weights, increased postimplantation loss). Equivocal findings for axial skeletal malformations were observed in three fetuses at 500 mg/kg. To better understand if these malformations were related to treatment with lersivirine, a follow-up rabbit embryo-fetal development study was performed with 1000 mg/kg/day lersivirine (500 mg/kg BID, 12-hr interdose interval) for two different 3-day windows, GDs 8 to 10 or GDs 11 to 13, which represent the sensitive windows of axial skeletal development in rabbits. Control rabbits were administered vehicle following the same dosing regimen from GDs 8 to 13. Cesarean sections were performed on GD 29, and fetal skeletons were examined for the potential of lersivirine to cause skeletal malformations in rabbits. At maternal exposure levels higher than the initial study, lersivirine did not induce fetal skeletal malformations when administered in the sensitive windows of axial skeletal development. The results of these studies indicate that lersivirine did not exhibit any evidence of teratogenicity in rabbits.Birth Defects Research Part B Developmental and Reproductive Toxicology 06/2012; 95(3):250-61. DOI:10.1002/bdrb.21014 · 0.77 Impact Factor
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ABSTRACT: Lersivirine is a second-generation nonnucleoside reverse transcriptase inhibitor undergoing clinical development for the treatment of HIV-1. An embryo-fetal developmental toxicity study was performed to evaluate the maternal and developmental toxicity of lersivirine in pregnant mice. Mated Crl:CD1(ICR) mice were administered 0, 150, 350, and 500 mg/kg lersivirine once daily by oral gavage on gestation days 6 to 17, followed by cesarean section on gestation day 18. The first 2 days of dosing for the high-dose group were done at 250 mg/kg to allow induction of hepatic metabolizing enzymes, after which the dose was increased to 500 mg/kg/day. This dosing paradigm allowed for maintenance of exposure in the high-dose group despite the considerable autoinduction that occurs in rodents following lersivirine treatment. Lersivirine did not cause an increase in external, visceral, or skeletal malformations. Intrauterine growth retardation, demonstrated by reduced fetal body weights and increased variations associated with delayed skeletal ossification, was noted at 350 and 500 mg/kg/day. The results of these studies indicate that lersivirine is not teratogenic in mice.Birth Defects Research Part B Developmental and Reproductive Toxicology 06/2012; 95(3):225-30. DOI:10.1002/bdrb.21008 · 0.77 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate cases of mother-to-child transmission of HIV-1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention. METHODS: Pregnant women infected with HIV-1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV-1 infection status after March 1, 2006. RESULTS: Of 711 eligible mothers, 10 delivered infants infected with HIV-1. The transmission rate was 1.4% (95% CI, 0.7-2.6). Timing of transmission was in utero or intrapartum (n=5), intrapartum (n=2), intrapartum or early postnatal (n=1), and unknown (n=2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV-1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding. CONCLUSION: Early knowledge of HIV-1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother-to-child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22-27, 2012); abstract WEPE163.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 07/2012; 119(1):70-75. DOI:10.1016/j.ijgo.2012.05.026 · 1.54 Impact Factor