Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT.NICHD (NICHD)(Brazilian AIDS Prevention Trials International Network), NIAID/ NIHNational Institute of Allergy and Infectious Diseases (NIAID)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Institute of Mental Health (NIMH)Boehringer Ingelheim Pharmaceuticals Inc. (BIPI)GlaxoSmithKline, on behalf of ViiV HealthcareCepheid for the testing of CTNG in a prior HPTNUCLA Children's Discovery and Innovation Institute (CDI) through the Harry Winston Fellowship AwardUCLA AIDS InstituteUCLA Center for AIDS Research (CFAR) NIH/ NIAIDUCLA Pediatric AIDS Coalition, and WestatNIH/NICHDDavid Geffen UCLA Sch Med, Los Angeles, CA 90095 USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz FIOCRUZ, Rio De Janeiro, RJ, BrazilUS Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USAElizabeth Glaser Pediat AIDS Fdn, Washington, DC USAHosp Geral Nova Iguacu, Nova Iguacu, RJ, BrazilHosp Fed Servidores Estado, Rio De Janeiro, RJ, BrazilUniv Witwatersrand, SAMRC & Perinatal HIV Res Unit, Johannesburg, South AfricaStellenbosch Univ, Tygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Sao Paulo, BrazilFdn Maternal & Infant Hlth FUNDASAMIN, Buenos Aires, DF, ArgentinaUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAUCLA, Fielding Sch Publ Hlth, Los Angeles, CA USAUCSD Sch Med, La Jolla, CA USAUC Davis Sch Med, Davis, CA USABoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilNICHD (NICHD): HHSN267200800001C, N01-HD-8-0001Brazilian AIDS Prevention Trials International Network: NIAID/ NIH [U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632, UM1AI068632, UM1AI068616, UM1AI106716NIMH: AI068632NG in a prior HPTN :040UCLA Center for AIDS Research (CFAR) NIH/ NIAID: AI02869, AI28697NIH/NICHD: HHSN275201300003CWeb of Scienc

Characteristics of the Sample Adequacy Control (SAC) in the Cepheid Xpert® CT/NG Assay in Female Urine Specimens

Made available in DSpace on 2015-04-08T14:09:57Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) mariza_morgadoetal_IOC_2014.pdf: 1843908 bytes, checksum: bfc9e7b4bbe85317564c2073d3a1d8a7 (MD5) Previous issue date: 2014University of California. Fielding School of Public Health. Department of Epidemiology. Los Angeles, USA.University of California. David Geffen UCLA School of Medicine. USA.University of California. David Geffen UCLA School of Medicine. USA.University of California. David Geffen UCLA School of Medicine. USA.Hospital Geral de Nova Iguaçu. Nova Iguaçu, RJ, Brazil.Hospital Federal dos Servidores do Estado. Rio de Janeiro, Brazil.University of California. David Geffen UCLA School of Medicine. USA.Fundação Oswaldo Cruz. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.National Institutes of Health. 4Eunice Kennedy Shriver National Institute of Child Health and Human Development. USA.Background: The Xpert® CT/NG (Cepheid Sunnyvale, CA) is a rapid, fully automated real-time polymerase chain reaction test that simultaneously detects Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). It has high sensitivity and specificity, but also includes a Specimen Adequacy Control (SAC). SAC controls for false negative results by confirming adequate patient sample and appropriate testing conditions. SAC is quantified by its cycle threshold (Ct), the number of cycles required to detect the presence of a single copy human gene. A lower SAC indicates an earlier Ct and more human cellular material detected. Our objectives were to describe the frequency and distribution of SAC Ct values and observe any correlations with detected infections. Methods: Urine samples from 1382 HIV-1-infected pregnant women, collected at the time of labor/delivery underwent Xpert® CT/NG testing. Mean SAC Ct values and standard deviation (SD) were calculated. Student’s t-test was used to compare mean SAC Ct values to a reference of urine samples negative for CT and NG. Results: The urine CT positivity was 17.9% (248/1382) and NG, 4.6% (63/1382). The mean SAC Ct value in urine from women without CT or NG was 28.09 (SD: 4.12) and higher than the mean SAC Ct value for CT positive specimens (27.29, SD: 3.84(P=.0054)), NG positive specimens (26.23, SD: 3.09(P<.0001)), and specimens positive for both CT and NG (26.41, SD: 3.01(P=.0027)). Conclusion: Lower SAC Ct values were significantly associated with chlamydial and gonococcal infections. Further studies should be conducted to determine the utility of SAC Ct values for identifying the presence of increased human cellular material and infectio

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

Undervaccination of Perinatally HIV-infected and HIV-exposed Uninfected Children in Latin America and the Caribbean

Background: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared.Methods: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling.Results: of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models.Conclusions: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.NICHDUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, São Paulo, BrazilWestat Corp, Rockville, MD USAUniv São Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, BrazilHosp Infantil Mexico Dr Federico Gomez, Depto Infectol, Clin Inmunodeficiencias, Mexico City, DF, MexicoUniv W Indies, Dept Child & Adolescent Hlth, Kingston, JamaicaNatl Univ San Marcos Lima, Natl Inst Child Hlth, Lima, PeruNatl Univ San Marcos Lima, Fac Med, Lima, PeruHosp Fed Servidores Estado, Rio de Janeiro, BrazilUniv Buenos Aires, Fac Med, Buenos Aires, DF, ArgentinaEunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD 20892 USAUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, São Paulo, BrazilNICHD: N01-HD-3-3345NICHD: HHSN267200800001CNICHD: N01-HD-8-0001Web of Scienc

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

CITATION: Adachi, K. et al. 2018. Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission. PLoS ONE,13(1):e0189851, doi:10.1371/journal.pone.0189851.The original publication is available at https://journals.plos.org/plosoneBackground: Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology: Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results: A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1–3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5–7.7). Individually, maternal CMV (aOR 4.4 1.5–13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2–7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion: HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189851Publisher's versio

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUNDThe safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.METHODSWithin 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups).CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)NICHDHIV Prevention Trials NetworkNational Institute of Allergy and Infectious Diseases (NIAID)National Institute of Mental HealthUniv Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USAEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz Fiocruz, Lab Pesquisa Clin DST & AIDS, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, BrazilFundacao Oswaldo Cruz Fiocruz, Lab AIDS & Imunol Mol, Inst Oswaldo Cruz, Rio De Janeiro, BrazilFundacao Oswaldo Cruz Fiocruz, Lab Informacoes Saude, Inst Informacao Cient & Tecnol Saude, Rio De Janeiro, BrazilHosp Fed Servidores Estado, Rio De Janeiro, BrazilHosp Geral Nova Iguacu, Rio De Janeiro, BrazilUniv Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South AfricaChris Hani Baragwanath Hosp, Johannesburg, South AfricaUniv Stellenbosch, Cape Town, South AfricaTygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, BR-14049 Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Calif Davis, Davis, CA 95616 USAFdn Maternal & Infant Hlth, Buenos Aires, DF, ArgentinaBoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Sao Paulo, BrazilNICHD: HHSN267200800001CNICHD: N01-HD-8-0001National Institute of Allergy and Infectious Diseases (NIAID): U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632National Institute of Mental Health: AI068632Web of Scienc

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUND The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P &lt; 0.001 for both comparisons with the other groups). CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)NICHD [HHSN267200800001C, N01-HD-8-0001]NICHDHIV Prevention Trials NetworkHIV Prevention Trials NetworkNational Institute of Allergy and Infectious Diseases (NIAID)National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI047986, U01 AI068632]National Institute of Mental Health [AI068632]National Institute of Mental Healt

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