Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.

Objective: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.

Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States.

Methods: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum.

Predictors of Viremia in Postpartum Women on Antiretroviral Therapy.

Background: HIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study.

Methods: Women with pre-ART CD4 T-cell counts ≥400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART).

Predicting Viral Failure in Human Immunodeficiency Virus Perinatally Infected Youth With Persistent Low-Level Viremia on Highly Active Antiretroviral Therapy.

Background: Less than optimal adherence with antiretroviral therapy occurs commonly among human immunodeficiency virus HIV)-infected youth. In this study, our object was to identify patterns in the prefailure measurement of viral load (VL) that can reliably predict virological failure (VF) in HIV perinatally infected youth on highly active antiretroviral therapy (HAART).

Methods: We conducted a retrospective chart review of HIV-infected youth with low-level viremia (LLV), defined as an HIV VL between the lower limits of detection (20-75 copies/mL) and 1000 copies/mL.

Longitudinal Changes in Body Composition by Dual-energy Radiograph Absorptiometry Among Perinatally HIV-infected and HIV-uninfected Youth: Increased Risk of Adiposity Among HIV-infected Female Youth.

Background: Combination antiretroviral therapy has allowed youth with perinatal HIV infection (PHIV+) to live into adulthood, but many youth may experience metabolic and body composition changes that predispose to greater cardiovascular disease (CVD) risk. This longitudinal study evaluated changes in body composition measured by dual-energy radiograph absorptiometry (DXA) in a cohort of PHIV+ youth compared with HIV- controls over a 7-year period.

Methods: PHIV+ youth and HIV- controls were prospectively enrolled in a single-site study to assess nutrition and CVD risk.

Birth Weight and Preterm Delivery Outcomes of Perinatally vs Nonperinatally Human Immunodeficiency Virus-Infected Pregnant Women in the United States: Results From the PHACS SMARTT Study and IMPAACT P1025 Protocol.

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.

Associations Between Dietary Intake Before 6 Months of Age and Rapid Weight Gain Among HIV-exposed Uninfected Infants.

Introduction: HIV-exposed, uninfected (HEU) infants are potentially at risk for cardiovascular disease due to in utero exposures. Feeding practices of the infant could compound this risk. Few studies have, however, evaluated dietary intake of HEU infants.

Lymphocyte subsets in HIV-exposed uninfected infants and HIV-unexposed uninfected infants.

HEU infants had higher CD19 B cell counts and % than HUU infants after the first 3 months of life, suggesting a B cell immune response with intrauterine exposure to maternal HIV or other pathogens.

Missed Opportunities for Prevention of Mother-to-Child Transmission of Human Immunodeficiency Virus.

Objective: To identify missed opportunities for prevention of mother-to-child transmission of human immunodeficiency virus (HIV).

Methods: Data regarding HIV-infected children born between 2002 and 2009 to HIV-infected women enrolled in the U.S.

Complications and Route of Delivery in a Large Cohort Study of HIV-1-Infected Women-IMPAACT P1025.

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.

Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney Disease in Children and Youth With Perinatal HIV Infection.

APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.

Body mass index and waist circumference of HIV-infected youth in a Miami cohort: comparison to local and national cohorts.

Objectives: Human immunodeficiency virus (HIV)-infected youth are healthier because of effective antiretroviral therapies. We compared anthropometric measurements and prevalence of overweight and obesity between perinatally HIV-infected youth, a local HIV-uninfected comparison group, and 2007 to 2010 National Health and Nutrition Examination Survey (NHANES) data. In addition, we compared only African American HIV-infected youth with NHANES African Americans.

Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus.

Background: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy.

Methods And Results: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed.

Infant growth outcomes after maternal tenofovir disoproxil fumarate use during pregnancy.

Objective: To determine whether maternal use of tenofovir disoproxil fumarate for treatment of HIV in pregnancy predicts fetal and infant growth.

Methods: The study population included HIV-uninfected live-born singleton infants of mothers enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 (born 2002-2011) in the United States and exposed in utero to a combined (triple or more) antiretroviral regimen. Infant weight at birth and 6 months was compared between infants exposed and unexposed to tenofovir in utero using 2-sample t test, χ test, and multivariable linear and logistic regression models, including demographic and maternal characteristics.

Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America.

Introduction: Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late-stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi-agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis.

Laboratory Abnormalities Among HIV-Exposed, Uninfected Infants: IMPAACT Protocol P1025.

Background: Infant laboratory abnormalities have been associated with exposure to antiretrovirals and to trimethoprim/sulfamethoxazole (TMP/SMX).

Methods: We analyzed data from International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025, a prospective cohort study of human immunodeficiency virus type 1 (HIV)-infected women and their infants. Live-born, singleton, HIV-uninfected infants with at least 6 months of follow-up who represented the first pregnancy on study of HIV-infected mothers with at least 1 prenatal visit, CD4 count, and viral load during pregnancy and who used at least 1 antiretroviral during pregnancy were eligible for inclusion in this analysis.

Cardiac status of children infected with human immunodeficiency virus who are receiving long-term combination antiretroviral therapy: results from the Adolescent Master Protocol of the Multicenter Pediatric HIV/AIDS Cohort Study.

Importance: Prior to contemporary antiretroviral therapies (ARTs), children infected with human immunodeficiency virus (HIV) were more likely to have heart failure. This study suggests that highly active ART (HAART) does not appear to impair heart function.

Objective: To determine the cardiac effects of prolonged exposure to HAART on HIV-infected children.

Growth and body composition of uninfected children exposed to human immunodeficiency virus: comparison with a contemporary cohort and United States National Standards.

Objective: To compare growth and body composition of uninfected children exposed to HIV with a contemporary HIV-unexposed group and to US references.

Study Design: Uninfected children exposed to HIV under 2 years were enrolled into a longitudinal observational study and unexposed children under 2 years of age in a cross-sectional evaluation. Weights, lengths, head circumferences, skinfold thicknesses, and arm and thigh circumferences were measured and adjusted for age using Centers for Disease Control and National Health and Nutrition Examination Survey standards.

Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection.

Background: Tenofovir is associated with renal proximal tubule injury. Such toxicity has not been extensively studied in HIV-1-infected children, in whom tenofovir is increasingly used.

Methods: History, urine and blood were collected at regular intervals from 448 children and adolescents with perinatal HIV-1 infection followed in the Pediatric HIV/AIDS Cohort study.

Cardiac biomarkers in HIV-exposed uninfected children.

Objectives: To evaluate associations of cardiac biomarkers with in-utero antiretroviral drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children.

Design And Methods: We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal antiretroviral drug exposures, maternal-child characteristics, and echocardiographic parameters.

Results: Among 338 HEU children (mean age 4.

Has highly active antiretroviral therapy increased the time to seroreversion in HIV exposed but uninfected children?

Background: Since the introduction of highly active antiretroviral therapy (HAART) for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in pregnancy in the United States, the time of seroreversion in infants born to HIV-infected mothers has not been documented. The objective of this study was to determine the timing of clearance of HIV antibodies and to identify any associated biological and clinical factors.

Methods: A retrospective analysis of infants who remained uninfected after perinatal HIV exposure was performed.

Physical fitness in children infected with the human immunodeficiency virus: associations with highly active antiretroviral therapy.

Obesity, sedentary lifestyles, and antiretroviral therapies may predispose HIV-infected children to poor physical fitness. Estimated peak oxygen consumption (VO(2) peak), maximal strength and endurance, and flexibility were measured in HIV-infected and uninfected children. Among HIV-infected children, anthropometric and HIV disease-specific factors were evaluated to determine their association with VO(2) peak.

Associations of cytokines, sleep patterns, and neurocognitive function in youth with HIV infection.

Youth infected with HIV at birth often have sleep disturbances, neurocognitive deficits, and abnormal psychosocial function which are associated with and possibly resulted from elevated blood cytokine levels that may lead to a decreased quality of life. To identify molecular pathways that might be associated with these disorders, we evaluated 38 HIV-infected and 35 uninfected subjects over 18-months for intracellular cytokine levels, sleep patterns and duration of sleep, and neurodevelopmental abilities. HIV infection was significantly associated with alterations of intracellular pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12), sleep factors (total time asleep and daytime sleep patterns), and neurocognitive factors (parent and patient reported problems with socio-emotional, behavioral, and executive functions; working memory-mental fatigue; verbal memory; and sustained concentration and vigilance.

Prevalence of congenital anomalies in infants with in utero exposure to antiretrovirals.

Background: Although use of efficacious interventions, including antiretrovirals (ARVs), has dramatically reduced the rate of mother-to-child transmission of human immunodeficiency virus, the safety of in utero ARV exposure remains of concern.

Methods: Data regarding 1112 infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 born between 2002 and 2007 were analyzed for this study. Congenital anomalies were classified based on the Metropolitan Atlanta Congenital Defects Program guidelines.

Mode of delivery and infant respiratory morbidity among infants born to HIV-1-infected women.

Objective: To estimate risk of infant respiratory morbidity associated with cesarean delivery before labor and ruptured membranes among HIV-1-infected women.

Methods: In a prospective cohort study of HIV-1-infected women and their infants, mode of delivery was determined by clinicians at the participating sites. For this analysis, "elective cesarean delivery" was defined as any cesarean delivery, regardless of gestational age, without labor and with duration of ruptured membranes of less than 5 minutes.

Biomarkers of vascular dysfunction in children infected with human immunodeficiency virus-1.

Background: : We compared biomarkers of vascular dysfunction among HIV-infected children to a demographically similar group of uninfected children and determined factors associated with these biomarkers.

Methods And Results: : We measured several biomarkers of vascular dysfunction: C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein -1 (MCP-1) (inflammation); fibrinogen and P-selectin (coagulant dysfunction); soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin (endothelial dysfunction); and leptin (metabolic dysfunction). Anthropometry, body composition, CD4%, HIV viral load, and antiretroviral therapy were recorded.