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In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization.
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Hemodinámica/fisiología , Modelos Cardiovasculares , Programas Informáticos , Síndrome de Alagille/fisiopatología , Síndrome de Alagille/cirugía , Vasos Sanguíneos/anatomía & histología , Vasos Sanguíneos/diagnóstico por imagen , Vasos Sanguíneos/fisiología , Biología Computacional , Simulación por Computador , Análisis de Elementos Finitos , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Imagenología Tridimensional , Trasplante de Hígado/efectos adversos , Imagen por Resonancia Magnética/estadística & datos numéricos , Modelos Anatómicos , Modelación Específica para el Paciente , Complicaciones Posoperatorias/etiología , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND: To evaluate the frequency and associated characteristics of chronic comorbid conditions and obstetrical complications among pregnant women with human immunodeficiency virus (HIV) and receiving antiretroviral therapy (ART) in comparison to those without HIV. METHODS: We compared 2 independent concurrent US pregnancy cohorts: (1) with HIV (International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1025, 2002-2013) and (2) without HIV (Consortium for Safe Labor Study, 2002-2007). Outcomes were ≥2 chronic comorbid conditions and obstetrical complications. For women with HIV, we assessed whether late prenatal care (≥14 weeks), starting ART in an earlier era (2002-2008), and a detectable viral load at delivery (≥400 copies/mL) were associated with study outcomes. RESULTS: We assessed 2868 deliveries (nâ =â 2574 women) with HIV and receiving ART and 211â 910 deliveries (nâ =â 193â 170 women) without HIV. Women with HIV were more likely to have ≥2 chronic comorbid conditions versus those without HIV (10 vs 3%; adjusted OR [AOR]: 2.96; 95% CI: 2.58-3.41). Women with HIV were slightly less likely to have obstetrical complications versus those without HIV (both 17%; AOR: .84; 95% CI: .75-.94), but secondarily, higher odds of preterm birth <37 weeks. Late entry to prenatal care and starting ART in an earlier era were associated with a lower likelihood of ≥2 chronic comorbidities and obstetrical complications; detectable viral load at delivery was associated with a higher likelihood of obstetric complications. CONCLUSIONS: Pregnant women with HIV receiving ART have more chronic comorbid conditions, but not necessarily obstetrical complications, than their peers without HIV.
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Fármacos Anti-VIH , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Fármacos Anti-VIH/efectos adversos , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Mujeres Embarazadas , Estados Unidos/epidemiología , Carga ViralRESUMEN
BACKGROUND: Pregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined. METHODS: We compared preterm delivery and birth weight (BW) outcomes (low BW [LBW], <2500 g), small-for-gestational-age [SGA], and BW z scores [BWZ]) in HIV-exposed uninfected infants of PHIV vs nonperinatally HIV-infected (NPHIV) pregnant women in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities or International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 studies. Mixed effects models and log binomial models were used to assess the association of maternal PHIV status with infant outcomes. Age-stratified analyses were performed. RESULTS: From 1998 to 2013, 2270 HIV-infected pregnant women delivered 2692 newborns (270 born to PHIV and 2422 to NPHIV women). PHIV women were younger, (mean age 21 vs 25 years, P < .01) and more likely to have a pregnancy CD4 count <200 cells/mm3 (19% vs 11%, P = .01). No associations between maternal PHIV status and preterm delivery, SGA, or LBW were observed. After adjustment, BWZ was 0.12 lower in infants of PHIV vs NPHIV women (adjusted mean, -0.45 vs -0.33; P = .04). Among women aged 23-30 years (n = 1770), maternal PHIV was associated with LBW (aRR = 1.74; 95% confidence interval, 1.18, 2.58; P < .01). CONCLUSION: The overall lack of association between maternal PHIV status and preterm delivery or infant BW outcomes is reassuring. The higher rates of LBW observed in PHIV women aged 23-30 years warrants further mechanism-based investigations as this is a rapidly growing and aging population worldwide. CLINICAL TRIALS REGISTRATION: PHACS SMARTT study, NCT01310023. CLINICAL TRIALS REGISTRATION: IMPAACT 1025, NCT00028145.
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Peso al Nacer , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/sangre , Humanos , Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Embarazo , Estudios Prospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women. OBJECTIVE: We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. STUDY DESIGN: We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. RESULTS: This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P < .01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to 1-log reduction was 7 days (IQR, 6-10) in the INSTI group vs 11 days (IQR, 10-14) in the non-INSTI group (P < .01). CONCLUSION: ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , VIH , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , ARN Viral/sangre , Carga Viral/efectos de los fármacos , Adulto , Quimioterapia Combinada/métodos , Femenino , Edad Gestacional , Inhibidores de la Proteasa del VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Oxazinas , Piperazinas , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Piridonas , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is a risk factor for mother-to-child transmission and poor maternal health. OBJECTIVE: To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy. DESIGN: Multicenter observational study. (ClinicalTrial.gov: NCT00028145). SETTING: 67 U.S. AIDS clinical research sites. PATIENTS: Pregnant women with HIV who initiated HAART during pregnancy. MEASUREMENTS: Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery. RESULTS: Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable VL at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P = 0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P < 0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P = 0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P = 0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P = 0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P = 0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery. LIMITATION: Data on many covariates were incomplete because women entered the study at varying times during pregnancy. CONCLUSION: A total of 13.1% of women who initiated HAART during pregnancy had detectable VL at delivery. The timing of HAART initiation and prenatal care, along with medication adherence during pregnancy, were associated with detectable VL at delivery. Social factors, including ethnicity and education, may help identify women who could benefit from focused efforts to promote early HAART initiation and adherence. PRIMARY FUNDING SOURCE: U.S. Department of Health and Human Services.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Carga Viral , Adolescente , Adulto , Escolaridad , Femenino , Infecciones por VIH/etnología , VIH-1/genética , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Cumplimiento de la Medicación , Paridad , Embarazo , Complicaciones Infecciosas del Embarazo/etnología , Tercer Trimestre del Embarazo , Atención Prenatal , ARN Viral/sangre , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only (n = 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.).
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Anticonceptivos Sintéticos Orales/efectos adversos , Anticonceptivos Sintéticos Orales/farmacología , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Acetato de Medroxiprogesterona/efectos adversos , Acetato de Medroxiprogesterona/farmacología , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Adolescente , Preparaciones de Acción Retardada , Interacciones Farmacológicas , Femenino , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/farmacocinética , Humanos , Lopinavir/farmacocinética , Persona de Mediana Edad , Ovulación/efectos de los fármacos , Progesterona/sangre , Ritonavir/farmacocinética , Adulto JovenRESUMEN
BACKGROUND: Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the differences among studies. METHODS: In total, 777 human immunodeficiency virus (HIV)-infected pregnant women in a prospective cohort who were not receiving antiretroviral (ARV) treatment at conception were studied. Births <37 weeks gestation were reviewed, and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (<2500 g) were evaluated by using multivariable logistic regression. RESULTS: Of the study population, 558 (72%) received combination ARV with PI during pregnancy, and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth, compared to ARV without PI (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.70-2.12). Sensitivity analyses that included women who received ARV prior to pregnancy also did not identify a significant association (OR, 1.34; 95% CI, 0.84-2.16). Low birth weight results were similar. CONCLUSIONS: No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines that promote consideration of combination ARV for all HIV-infected pregnant women.
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Antirretrovirales/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Nacimiento Prematuro/etiología , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Distribución de Chi-Cuadrado , Estudios de Cohortes , Femenino , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Modelos Logísticos , Embarazo , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/virología , Atención Prenatal/métodos , Estudios Prospectivos , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
Obstetrician-gynecologists in the United States have little clinical experience with the epidemiology, pathophysiology, diagnosis, and treatment of Chagas disease. The number of US parturients born in Central and South America has continued to increase over the last 20 years, making US obstetricians more and more likely to care for Chagas-infected mothers who may never be identified until dealing with long-term consequences of the disease. A literature search demonstrates that few US obstetric care providers recognize the risk of vertical transmission for the neonate and the missed opportunity of infant treatment to decrease disease prevalence. Most women will be asymptomatic during pregnancy, as will their neonates, making routine laboratory screening a necessity for the identification of at-risk neonates. While the benefits of treating asymptomatic women identified in pregnancy are not as clear as the benefits for the infants, future health screenings for evidence of the progression of Chagas disease may be beneficial to these families. The literature suggests that screening for Chagas in pregnancy in the US can be done in a cost-effective way. When viewed through an equity lens, this condition disproportionately affects families of lower socioeconomic means. Improved education of healthcare providers and appropriate resources for diagnosis and treatment can improve this disparity in health outcomes.
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This paper presents a stabilized formulation for the generalized Navier-Stokes equations for weak enforcement of essential boundary conditions. The non-Newtonian behavior of blood is modeled via shear-rate dependent constitutive equations. The boundary terms for weak enforcement of Dirichlet boundary conditions are derived via locally resolving the fine-scale variational equation facilitated by the Variational Multiscale (VMS) framework. The proposed method reproduces the consistency and stabilization terms that are present in the Nitsche type approaches. In addition, for the shear-rate fluids, two more boundary terms appear. One of these terms is the viscosity-derivative term and is a function of the shear-rate, while the other term is a zeroth-order term. These terms play an important role in attaining optimal convergence rates for the velocity and pressure fields in the norms considered. A most significant contribution is the form of the stabilization tensors that are also variationally derived. Employing edge functions the edge stabilization tensor is numerically evaluated, and it adaptively adjusts itself to the magnitude of the boundary residual. The resulting formulation is variationally consistent and the weakly imposed no-slip boundary condition leads to higher accuracy of the spatial gradients for coarse boundary-layer meshes when compared with the traditional strongly imposed boundary conditions. This feature of the present approach will be of significance in imposing interfacial continuity conditions across non-matching discretizations in blood-artery interaction problems. A set of test cases is presented to investigate the mathematical attributes of the method and a patient-specific case is presented to show its clinical relevance.
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Viscosidad , Humanos , Estrés MecánicoRESUMEN
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a public health concern, mainly among countries in South and Central America. However, despite the large number of immigrants from endemic countries living in the USA, awareness of CD is poor in the medical community, and therefore it is significantly underdiagnosed. To avoid the catastrophic cardiac complications of CD and to prevent maternal-fetal transmission, widespread educational programs highlighting the need for diagnosis are urgently needed.
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Introduction: Learning to elicit a sexual history and counsel patients on sexual pain aligns with the Association of Professors of Gynecology and Obstetrics clerkship objectives. This topic can be challenging to cover due to lack of exposure in clinical encounters and inadequate coverage in preclinical studies. Methods: Second-year medical students in the OB/GYN clerkship participated in a standardized patient (SP) encounter on dyspareunia, receiving formative feedback on sexual history taking, differential diagnosis and management plan, and their SP's comfort during the encounter. Student feedback was obtained mid- and postclerkship. Summary statistics and regression models comparing SP encounter scores with shelf exam and clerkship scores are reported. Results: From September 2018 through July 2019, 101 students completed the encounter. Students asked an average of 3.9 of 13 sexual history questions. Sixty-six percent of students identified a correct diagnosis; 48% provided a management plan. The majority of students were very good or excellent at creating a safe environment. Most reported the encounter enhanced their learning (62%) and identified knowledge gaps (72%). SP encounter score was not associated with shelf exam score or clerkship letter grade but was associated with final clerkship score (unadjusted ß = 0.2, p = .009; adjusted ß = 0.1, p = .2). A summary didactic session was developed following student feedback. Discussion: This SP encounter and summary didactic session allowed students to improve their sexual history taking and may be associated with clerkship performance. These skills are necessary to advocate for patients with sensitive complaints across specialties.
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Prácticas Clínicas , Dispareunia , Ginecología , Obstetricia , Estudiantes de Medicina , Femenino , Ginecología/educación , Humanos , Anamnesis , Obstetricia/educaciónRESUMEN
BACKGROUND: To investigate the effect of exposure to protease inhibitor (PI) therapy in utero on cord blood lipids in infants born to mothers enrolled in AIDS Clinical Trials Group protocol 5084, a prospective, multicentre, observational study of antiretroviral therapy (ART) during pregnancy. METHODS: Clinical outcome was determined in 80 infants born to women treated with PIs and 73 infants born to women treated with other antiretrovirals during pregnancy. Cord blood serum from 117 of these infants was assayed for total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1 (apoA1), apolipoprotein B100 (apoB) and lipoprotein (a). Covariates considered in the analysis included race/ethnicity, gestational age, infant gender, infant birth weight, mode of delivery, maternal tobacco and alcohol use, post-partum body mass index, and ART duration. RESULTS: Cord blood total and HDL cholesterol, triglyceride, apoA1, apoB, lipoprotein (a) and apoB/apoA1 ratio were not different between the two groups. Cord blood lipid levels in these HIV-exposed infants were similar to those reported in other neonatal cohorts. Controlling for race/ethnicity, infants born to women treated with PIs had higher LDL cholesterol than those born to women not treated with PIs (29 mg/dl versus 27 mg/dl, P = 0.006). CONCLUSION: Only LDL cholesterol was significantly higher in the cord blood of PI-exposed infants versus those not exposed to PIs in utero. As the difference between the two groups was small, the clinical relevance of the effect of maternal PI treatment on infant LDL cholesterol levels at birth is not clear.
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Antirretrovirales/uso terapéutico , LDL-Colesterol/sangre , Sangre Fetal/metabolismo , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1 , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Antirretrovirales/efectos adversos , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , HDL-Colesterol/sangre , Quimioterapia Combinada , Femenino , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Recién Nacido , Lipoproteína(a)/sangre , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Resultado del Tratamiento , Triglicéridos/sangre , Estados UnidosRESUMEN
BACKGROUND: The effects of gestational nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondrial DNA (mtDNA) are controversial. The effects of mtDNA depletion on mitochondrial function have not been assessed. METHOD: In peripheral blood mononuclear cells (PBMCs) from infants born to HIV-infected women and infants born to HIV-1-uninfected women, mtDNA copy numbers were determined by quantitative PCR; nuclear (COXIV)- and mitochondrial (COXII)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase (COX or complex IV) were quantified by Western blot. RESULTS: Overall, 86 infants born to HIV-infected women and 50 controls were studied. HIV-infected mothers had a median CD4 count of 506 cells/microL; 59% had HIV RNA 50 copies/mL. No infant had clinical evidence of mitochondrial disease. The birth weight was lower (p = .016) and the body length higher (p = .002) in the HIV-exposed newborns. Eighty-one HIV-infected women had received gestational NRTIs (median duration 162 days). Median mtDNA copies/PBMC in the HIV-exposed infants were 505 (range, 120-1365) vs. 213 (27-426) in controls (p < .001). COX II/IV ratios were similar in both groups. Although mtDNA levels correlated inversely with maternal lactate, mitochondrial indices did not correlate with maternal CD4+ count, HIV RNA, smoking, or alcohol consumption. CONCLUSION: We found elevated mtDNA copy numbers in PBMC of infants born to HIV-infected women, the majority of whom received NRTI-based therapy, when compared to those born to healthy HIV-negative controls, but there was no difference in mtDNA-encoded respiratory chain protein. The clinical consequence of these findings is unknown and requires further investigations.
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ADN Mitocondrial/análisis , Infecciones por VIH/tratamiento farmacológico , Leucocitos Mononucleares/química , Leucocitos Mononucleares/enzimología , Proteínas Mitocondriales/análisis , Complicaciones Infecciosas del Embarazo , Adolescente , Adulto , Peso al Nacer , Western Blotting , Estatura , Recuento de Linfocito CD4 , Citocromos c/análisis , Femenino , VIH-1/aislamiento & purificación , Humanos , Recién Nacido , Reacción en Cadena de la Polimerasa/métodos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , ARN Viral/sangre , Carga ViralRESUMEN
IMPORTANCE: Intrahepatic cholestasis of pregnancy (ICP) complicates approximately 0.2% to 2% of pregnancies and can lead to increased fetal risks in pregnancy. OBJECTIVE: This review aims to increase the knowledge of women's health care providers regarding the diagnosis, management, and fetal risks associated with ICP. RESULTS: The diagnosis of ICP is based on symptoms of pruritus that typically include the palms and soles, as well as elevated bile acid levels. Other liver function tests such as alanine aminotransferase and aspartate aminotransferase are also frequently elevated, and other causes of liver dysfunction should be ruled out. Fetal risks of ICP include increased risk of preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome, or stillbirth. There is evidence that as bile acid levels increase, so does the risk of adverse neonatal outcomes. Ursodeoxycholic acid treatment has been shown to improve maternal pruritus symptoms, as well as biochemical tests, but no treatment has been shown to definitively improve fetal outcomes. CONCLUSIONS AND RELEVANCE: Providers should be aware of the signs and symptoms of ICP and provide accurate diagnosis and management of affected women. Women with a diagnosis of ICP should be treated with ursodeoxycholic acid to improve maternal symptoms. Given the increased risk of stillbirth in the setting of ICP, delivery may be considered at 37 weeks' gestation.
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Colagogos y Coleréticos/uso terapéutico , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/tratamiento farmacológico , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/tratamiento farmacológico , Diagnóstico Prenatal/métodos , Ácido Ursodesoxicólico/uso terapéutico , Adulto , Colestasis Intrahepática/complicaciones , Manejo de la Enfermedad , Femenino , Humanos , Pruebas de Función Hepática , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/etiología , Prurito/diagnóstico , Prurito/etiología , Factores de Riesgo , MortinatoRESUMEN
OBJECTIVE: To describe patterns and factors associated with mode of delivery among pregnant women with human immunodeficiency virus (HIV) infection in the United States in relation to evolving HIV-in-pregnancy guidelines. METHODS: We conducted an analysis of two observational studies, Pediatric AIDS Clinical Trials Group and International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1025, which enrolled pregnant women with HIV infection from 1998 to 2013 at more than 60 U.S. acquired immunodeficiency syndrome clinical research sites. Multivariable analyses of factors associated with an HIV-indicated cesarean delivery (ie, for prevention of mother-to-child transmission) compared with other indications were conducted and compared according to prespecified time periods of evolving HIV-in-pregnancy guidelines: 1998-1999, 2000-2008, and 2009-2013. RESULTS: Among 6,444 pregnant women with HIV infection, 21% delivered in 1998-1999, 58% in 2000-2008, and 21% in 2009-2013; 3,025 (47%) delivered by cesarean. Cesarean delivery increased from 30% in 1998 to 48% in 2013. Of all cesarean deliveries, repeat cesarean deliveries increased from 16% in 1998 to 42% in 2013; HIV-indicated cesarean deliveries peaked at 48% in 2004 and then dropped to 12% by 2013. In multivariable analyses, an HIV diagnosis during pregnancy, initiation of antiretroviral therapy in the third trimester, a plasma viral load 500 copies/mL or greater, and delivery between 37 and 40 weeks of gestation increased the likelihood of an HIV-indicated cesarean delivery. In analyses by time period, an HIV diagnosis during pregnancy, initiation of antiretroviral therapy in the third trimester, and a plasma viral load of 500 copies/mL or greater were progressively more likely to be associated with an HIV-indicated cesarean delivery over time. CONCLUSION: Almost 50% of pregnant women with HIV infection underwent cesarean delivery. Over time, the rate of repeat cesarean deliveries increased, whereas the rate of HIV-indicated cesarean deliveries decreased; cesarean deliveries were more likely to be performed in women at high risk of mother-to-child transmission. These findings reinforce the need for both early diagnosis and treatment of HIV infection in pregnancy and the option of vaginal delivery after cesarean among pregnant women with HIV infection.
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Fármacos Anti-VIH/uso terapéutico , Cesárea Repetida , Cesárea , Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Adulto , Cesárea/métodos , Cesárea/estadística & datos numéricos , Cesárea Repetida/métodos , Cesárea Repetida/estadística & datos numéricos , Parto Obstétrico/métodos , Diagnóstico Precoz , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Humanos , Análisis Multivariante , Estudios Observacionales como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/terapia , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the effect of protease inhibitors on lipid and lactate levels and gastrointestinal symptoms in pregnancy. METHODS: Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (ACTG) A5084 was an observational cohort study of human immunodeficiency virus (HIV)-infected pregnant women. Women recruited between 20 and 34 weeks of gestation were required to be on a stable, highly active antiretroviral therapy (HAART) regimen, stratified by protease inhibitor compared with no protease inhibitor regimens. Interval history was assessed, and lipid and lactate levels were drawn every 8 weeks during pregnancy and 12 weeks postpartum, with levels closest to delivery and postpartum used for analysis. Statistical comparisons used Kruskal-Wallis and Fisher exact tests. RESULTS: One-hundred fifty-eight women were evaluated. Total cholesterol levels (median 230 mg/dL, interquartile range [197, 259], compared with 212 [179, 246] mg/dL, P=.042) and triglycerides (median 224 mg/dL, interquartile range [187, 288], compared with 185 [142, 230] mg/dL, P<.001] were elevated in the protease inhibitor group during pregnancy and remained higher in this group after delivery (total cholesterol 185 [163, 224] mg/dl compared with 171 [140, 190] mg/dL, P<.004; triglycerides 122 [87, 175] mg/dL compared with 89 [66, 150] mg/dL, P=.02). No difference was seen in lactate levels or rates of gastrointestinal symptoms between groups. Obstetric outcomes were similar between the two groups. A higher number of low birth weight infants were born to women in the highest twentieth percentile of triglycerides compared with the lowest across medication groups. CONCLUSION: Cholesterol and triglycerides were higher in protease inhibitor-treated women in pregnancy. Lactate and gastrointestinal symptoms were not different. A higher number of low birth weight infants were noted in women with high triglycerides, but other elevated lipid levels did not affect pregnancy outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00017797 LEVEL OF EVIDENCE: II.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Inhibidores de Proteasas/farmacología , Adolescente , Adulto , HDL-Colesterol/sangre , HDL-Colesterol/efectos de los fármacos , Estudios de Cohortes , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Ácido Láctico/sangre , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Resultado del Embarazo , Triglicéridos/sangreRESUMEN
OBJECTIVE: The objective of the study was to determine whether protease inhibitors increase glucose intolerance and insulin resistance in pregnancy. STUDY DESIGN: In this multicenter, prospective, observational study, 149 human immunodeficiency virus-1-infected pregnant women had fasting insulin, glucose, and C-peptide measured followed by a 1 hour, 50 g glucose test. Glucose intolerance was defined as a 1 hour glucose greater than 130 mg/dL. Glucose intolerance, homeostasis model assessment of insulin resistance and pancreatic beta-cell function, and pregnancy outcomes were compared between those taking protease inhibitors and those not. RESULTS: Fifty-seven of 149 subjects (38%) had glucose intolerance. Body mass index, Hispanic ethnicity, and maternal age, but not protease inhibitors, were associated with glucose intolerance. There were no differences in insulin resistance, beta-cell function, or pregnancy outcome associated with protease inhibitor use. CONCLUSIONS: Protease inhibitors do not increase risk of glucose intolerance or insulin resistance among pregnant women.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Adolescente , Adulto , Glucemia , Diabetes Gestacional/prevención & control , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Edad Gestacional , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Infecciones por VIH/diagnóstico , Humanos , Recién Nacido , Modelos Logísticos , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Estadísticas no ParamétricasRESUMEN
Zidovudine-based antiretroviral therapies (ARTs) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from approximately 25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposure. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIV-infected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; three received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery and from infants at 1-3 days, 4-6 weeks, and 4-6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Tenfold increases in %MN-RET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in three women and infants who received prenatal ART without ZDV. Specifically, mean %MN-RET in cord blood of ZDV-exposed infants was 1.67 +/- 0.34 compared with 0.16 +/- 0.06 in non-ZDV ART-exposed infants (P = 0.006) and 0.12 +/- 0.02 in control cord bloods (P < 0.0001). %MN-RET in ZDV-exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacentalZDV exposure is genotoxic in humans. Long-term monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Micronúcleos con Defecto Cromosómico/inducido químicamente , Mutágenos/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Zidovudina/efectos adversos , Adolescente , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Intercambio Materno-Fetal , Periodo Posparto , Embarazo , Reticulocitos/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate complications of cesarean section in a cohort of HIV-infected pregnant women. METHODS: IMPAACT P1025 is a prospective cohort study of HIV-1-infected women and infants, enrolled 2002-2013, at clinical sites in the United States and Puerto Rico. Demographic, medical, and obstetric data were collected and analyzed including cesarean indications. The delivery route was categorized as elective cesarean (ECS) (before labor and <5 minutes before membrane rupture), nonelective cesarean (NECS) (all other cesareans) or vaginal delivery. Logistic regression models evaluated associations between delivery route and maternal intrapartum/postpartum morbidities. Composite morbidity of vaginal delivery was compared with ECS and NECS. RESULTS: This study included 2297 women. Of note, 99% used antiretroviral medication and 89% were on a combination antiretroviral therapy regimen; 84% had a HIV-1 viral load ≤400 copies per milliliter before delivery; 46% (1055) delivered vaginally, 35% (798) by ECS, and 19% (444) by NECS. Although interruption of HIV-1 infection was the second most frequent indication for cesarean after repeat cesarean, it decreased as an indication over time. There were no delivery-related maternal mortalities. Overall, 19% of women had ≥1 complication(s)-primarily wound complications (14%) or other infections (11%). Vaginal delivery had the lowest complication rate (13%), followed by ECS (23%), and highest NECS (28%) with an overall P < 0.001. HIV-1 mother-to-child transmission rates were low and did not differ by delivery mode group. CONCLUSIONS: HIV interruption as cesarean indicator declined during the study. Morbidity was more common in HIV-infected women delivering by NECS than ECS and lowest with vaginal delivery. CLINICAL TRIAL REGISTRATION: Prenatal and Postnatal Studies of Interventions for Prevention of Mother-To-Child Transmission https://clinicaltrials.gov/ct2/show/NCT00028145?term=impaact+1025&rank=2 NCT00028145.
Asunto(s)
Parto Obstétrico/efectos adversos , Infecciones por VIH/fisiopatología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo , Femenino , VIH-1 , Humanos , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVES: Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T-cell activation, T-cell regulation (Treg), and inflammation in HIV-infected women on combination antiretroviral regimen (cART). METHODS: Women with HIV plasma RNA ≤ 400 copies per milliliter on stable cART received DMPA and had immunologic and medroxyprogesterone acetate (MPA) measurements at baseline, 4 weeks [peak MPA concentration (Cmax)], and 12 weeks [highest MPA area under the concentration curve]. RESULTS: At baseline, among 24 women with median age of 32 years and 622 CD4(+) cells per microliter, ≥ 68% had HIV, varicella-zoster virus, phytohemagglutinin A and CD3/CD28 CMI measured by lymphocyte proliferation, and/or IFNγ/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFNγ varicella-zoster virus fluorospot at week 12. T-cell activation decreased after DMPA administration, reaching statistical significance at week 12 for CD4(+)CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGFß at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA Cmax and/or area under the concentration curve were significantly associated with increases of IFNγ HIV enzyme-linked ImmunoSpot, CD4+IL35+%, and CD4+TGFß+% Treg and decreases of plasma IL10 from baseline to weeks 4 and/or 12. CONCLUSIONS: A single dose of DMPA did not have immune-suppressive or pro-inflammatory effects in HIV-infected women on cART. Additional studies need to assess the effect of multiple doses.