Maternal antiretroviral use during pregnancy and infant congenital anomalies: the NISDI perinatal study

Principal investigators, co-principal investigators, study coordinators, coordinating center representatives, and NICHD staff include: Argentina: Buenos Aires: Marcelo H. Losso, Adriana S. Durán, Silvina Ivalo (Hospital General de Agudos José María Ramos Mejía); Brazil: Belo Horizonte: Jorge Pinto, Victor Melo, Fabiana Kakehasi (Universidade Federal de Minas Gerais); Caxias do Sul: Ricardo da Silva de Souza, Nicole Golin, Machline Paim Paganella (Universidade de Caxias do Sul/Secretaria Municipal de DST/AIDS de Caxias do Sul - Ambulatorio Municipal DST/AIDS); Nova Iguaçu: Jose Pilotto (Hospital Geral Nova de Iguaçu Setor de DST/AIDS; Porto Alegre: Ricardo da Silva de Souza, Breno Riegel Santos, Rita de Cassia Alves Lira (Universidade de Caxias do Sul/Hospital Conceição); Ricardo da Silva de Souza, Mario Peixoto, Marcelo Almeida (Universidade de Caxias do Sul/Hospital Fêmina); Regis Kreitchman, Debora Coelho Fernandes (Irmandade da Santa Casa de Misericórdia de Porto Alegre); Ribeirão Preto: Marisa M. Mussi-Pinhata, Geraldo Duarte, Carolina Sales V. Macedo, Maria A. do Carmo Rego (Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo); Rio de Janeiro: Ricardo Hugo S. Oliveira, Elizabeth S. Machado, Maria C. Chermont Sapia (Instituto de Puericultura e Pediatria Martagão Gesteira); Esau Custodio Joao, Leon Claude Sidi, Guilherme Amaral Calvet, Claudete Araújo Cardoso (Hospital dos Servidores do Estado); Beatriz Grinsztejn, Valdilea Veloso (Fiocruz, INI, Lapclin-AIDS); São Paulo: Regina Celia de Menezes Succi, Prescilla Chow Lindsey (Federal University of São Paulo); Peru: Lima: Jorge Alarcon (Instituto de Medicina Tropical “Daniel Alcides Carrion”-Division de Epidemiología), Carlos Velásquez Vásquez (Instituto Materno Perinatal), César Gutiérrez Villafuerte (Instituto de Medicina Tropical “Daniel Alcides Carrion”-Division de Epidemiología); Data Management and Statistical Center: Yolanda Bertucci, Laura Freimanis Hance, René Gonin, D. Robert Harris, Roslyn Hennessey, James Korelitz, Margot Krauss, Sharon Sothern, Sonia K. Stoszek (Westat, Rockville, MD, USA); NICHD: Rohan Hazra, Lynne Mofenson, Jack Moye, Jennifer S. Read, Heather Watts, Carol Worrell (Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA).Submitted by Fábio Marques ([email protected]) on 2018-11-21T18:00:06Z No. of bitstreams: 1 Maternal Antiretroviral Use during Pregnancy_Guilherme_Calvet_INI_Lapclin-AIDS_2010.pdf: 366876 bytes, checksum: 516d66ca20ecd4420f393bc6b5bb7aec (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-11-21T18:41:02Z (GMT) No. of bitstreams: 1 Maternal Antiretroviral Use during Pregnancy_Guilherme_Calvet_INI_Lapclin-AIDS_2010.pdf: 366876 bytes, checksum: 516d66ca20ecd4420f393bc6b5bb7aec (MD5)Made available in DSpace on 2018-11-21T18:41:02Z (GMT). No. of bitstreams: 1 Maternal Antiretroviral Use during Pregnancy_Guilherme_Calvet_INI_Lapclin-AIDS_2010.pdf: 366876 bytes, checksum: 516d66ca20ecd4420f393bc6b5bb7aec (MD5) Previous issue date: 2010NICHD Contract # N01-HD-3-3345 and # HHSN267200800001C (NICHD Control # N01-DK-8-0001).Hospital dos Servidores do Estado, Rio de Janeiro, Brasil.Hospital dos Servidores do Estado, Rio de Janeiro, Brasil./ Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Westat. Rockville, MD, USA.Westat. Rockville, MD, USA.Instituto Nacional de Perinatologia. Ciudad de México, México.Hospital José María Ramos Mejía. Buenos Aires, Argentina.University of the West Indies. Kingston, Jamaica.Universidad National Mayor de San Marcos. Lima, Perú.DHHS. National Institutes of Health. NICHD. CRMC. Pediatric, Adolescent, and Maternal AIDS Branch. Bethesda, MD, USA.DHHS. National Institutes of Health. NICHD. CRMC. Pediatric, Adolescent, and Maternal AIDS Branch. Bethesda, MD, USA.We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study

Mother-to-Child transmission of HCV among HIV/HCV Co-infected women

BACKGROUND: Maternal human immunodeficiency virus (HIV) coinfection has been associated with increased hepatitis C virus (HCV) mother-to-child transmission (MTCT). We hypothesized that HCV/HIV-coinfected women with well-controlled HIV disease would not have increased HCV MTCT. METHODS: The NISDI Perinatal and LILAC cohorts enrolled HIV-infected pregnant women and their infants in Latin America and the Caribbean. This substudy evaluated the HCV infection status of mothers at participating sites and their live born, singleton infants who had a 6-month postnatal visit by December 31, 2008. Mothers who were anti-HCV-positive, or who had CD4 counts (cells/mm(3)) <200 with detectable HCV RNA, were considered HCV-infected. All HCV-infected women were tested for HCV RNA. Infants with HCV RNA were considered HCV-infected. RESULTS: Of 1042 enrolled women, 739 (71%) mother-infant pairs met the inclusion criteria. Of the 739 women, 67 (9%) were anti-HCV-positive and 672 anti-HCV-negative [68 (10%) with CD4 counts <200; of these, 3 (4.4%) were HCV RNA-positive]. Therefore, our study population comprised 70 HCV-infected (47 with HCV RNA) and 669 HCV-uninfected women (and their infants). Factors associated with maternal HCV infection included unemployment (odds ratio [OR] = 2.58); tobacco (OR = 1.73) or marijuana (OR = 3.88) use during pregnancy; enrollment HIV viral load ([VL] copies/mL) ≥10 000 (OR = 2.27); HIV clinical disease stage C (OR = 2.12); and abnormal alanine aminotransferase (OR = 4.24) or aspartate aminotransferase (OR = 11.98). Four of 47 infants (8.5%) born to HCV-viremic women were HCV-infected, and all 4 mothers had HIV VL <1000 at hospital discharge after delivery. CONCLUSIONS: HCV MTCT among HIV/HCV-coinfected women with well-controlled HIV disease may be lower than reported in other coinfected populations. Studies with longer infant follow-up are needed.Fil: Checa Cabot, Claudia A.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Stoszek, Sonia K.. Westat; Estados UnidosFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Losso, Marcelo H.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Ivalo, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Peixoto, Mario F.. Hospital Femina. Vertical Transmission Prevention Unit; BrasilFil: Pilotto, José H.. Hospital Geral de Nova Iguaçu and Laboratorio de AIDS e Imunologia Molecular; BrasilFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Sidi, Leon C.. Hospital Federal dos Servidores do Estado; BrasilFil: Read, Jennifer. National Institutes of Health; Estados Unido

Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women

Objective.To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum. Methods.HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. Results.Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, 60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing. Conclusions.Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy. Clinical Trials Registration.NCT00825929 and NCT000422890.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Fosamprenavir with Ritonavir Pharmacokinetics during Pregnancy.

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 μg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P &lt; 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P &lt; 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0-12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P = 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P = 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P = 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P = 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (Cmin) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 μg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression