Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1.

HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes.

A review of post-caesarean infectious morbidity: how to prevent and treat.

Post-caesarean infectious complications result in significant maternal morbidity and mortality as well as increased readmissions and increased health care cost worldwide. This review provides a discussion of several risk factors that have been identified which predispose women to post-surgical infection. We also provide an overview of strategies for infection prevention including antibiotics, surgical techniques and negative pressure wound therapy.

Racial Disparities in Adverse Pregnancy Outcomes and Psychosocial Stress.

Objective: To assess the relationships between self-reported psychosocial stress and preterm birth, hypertensive disease of pregnancy, and small-for-gestational-age (SGA) birth and to assess the extent to which these relationships account for racial and ethnic disparities in these adverse outcomes.

Methods: Self-reported measures of psychosocial stress (perceived stress, depression, racism, anxiety, resilience, and social support) were collected during pregnancy among a racially and ethnically diverse cohort of women enrolled in a prospective observational study of nulliparous women with singleton pregnancies, from eight clinical sites across the United States, between October 2010 and May 2014. The associations of preterm birth, hypertensive disease of pregnancy, and SGA birth with the self-reported measures of psychosocial stress as well as with race and ethnicity were evaluated.

Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry.

Rationale: Assays to quantify antiretrovirals in hair samples are increasingly used to monitor adherence and exposure in both HIV prevention and treatment studies. Atazanavir (ATV) is a protease inhibitor used in combination antiretroviral therapy (ART). We developed and validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based method to quantify ATV in human hair, per the NIH Division of AIDS Clinical Pharmacology Quality Assurance (CPQA) program and the FDA bioanalytical method validation guidelines.

ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.

Background: Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine.

Methods: A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA ≥1000 and <500000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance.

Translational Systems Pharmacology Studies in Pregnant Women.

Pregnancy involves rapid physiological adaptation and complex interplay between mother and fetus. New analytic technologies provide large amounts of genomic, proteomic, and metabolomics data. The integration of these data through bioinformatics, statistical, and systems pharmacology techniques can improve our understanding of the mechanisms of normal maternal physiologic changes and fetal development.

Evaluation of PrediXcan for prioritizing GWAS associations and predicting gene expression.

Genome-wide association studies (GWAS) have been successful in facilitating the understanding of genetic architecture behind human diseases, but this approach faces many challenges. To identify disease-related loci with modest to weak effect size, GWAS requires very large sample sizes, which can be computational burdensome. In addition, the interpretation of discovered associations remains difficult.

Impact of Pregnancy History and 17-Hydroxyprogesterone Caproate on Cervical Cytokines and Matrix Metalloproteinases.

Objective:  The objective of this study was to evaluate the impact of pregnancy history and 17-hydroxyprogesterone caproate (17-OHPC) treatment on cervical fluid cytokines and matrix metalloproteinases (MMPs).

Study Design:  Cervical fluid was obtained between 16 and 24 weeks from women with only prior term births (controls,  = 26), women with one or more prior spontaneous preterm births (SPTBs) choosing to receive 17-OHPC (17-OHPC,  = 24), or to not receive 17-OHPC (refusers,  = 12). Cervical fluid collections were repeated 2, 4, and 8 weeks after the first sample and concentrations of MMPs and cytokines were measured by multiplex immune assay.

Race/ethnicity difference in the pharmacogenetics of bilirubin-related atazanavir discontinuation.

Background: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity.

Patients And Methods: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data.

Genetics of human susceptibility to active and latent tuberculosis: present knowledge and future perspectives.

Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Recent findings from studies of tuberculosis infection and of patients with Mendelian predisposition to severe tuberculosis have started to reveal human loci influencing tuberculosis outcomes.

Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.

Background: Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping.

Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load.

A systematic overview of the literature regarding group prenatal care for high-risk pregnant women.

Background: Group prenatal care (GPC) models have been gaining popularity in recent years. Studies of high-risk groups have shown improved outcomes. Our objective was to review and summarize outcomes for women in GPC for women with specific high-risk conditions.

Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians.

Nevirapine is metabolized by several hepatic cytochrome P450 (CYP) isoforms to generate four primary hydroxylated metabolites: 2-hydroxynevirapine, 3-hydroxynevirapine, 8-hydroxynevirapine, and 12-hydroxynevirapine. The present study characterized associations between genetic polymorphisms and metabolite ratios in HIV-infected Cambodians. We demonstrate associations between polymorphisms and metabolite ratios for both 3-hydroxynevirapine and 8-hydroxynevirapine, suggesting involvement of CYP2B6 in generating these metabolites.

HLA-B*14:02-Restricted Env-Specific CD8 T-Cell Activity Has Highly Potent Antiviral Efficacy Associated with Immune Control of HIV Infection.

Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8 T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9).

Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor-Based Regimens.

Background: With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy, persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients who switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression who switched from EFV/TDF/FTC to an INSTI-containing regimen.

Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles.

Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding specificities and binding pocket structure.

Survey of Provider Preferences Regarding the Route of Misoprostol for Induction of Labor at Term.

 To survey obstetrical provider preferences regarding use of misoprostol for induction of labor (IOL).  An anonymous 25-question survey was distributed at an American College of Obstetricians and Gynecologists (ACOG) joint District V and VII Meeting in 2014 to obstetrics providers. The same survey was sent electronically to local providers.

Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women.

Background: Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown.

Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes.

Background: Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes.

Objective: Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy.

Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health.

Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial.

Circumcision bleeding complications: neonatal intensive care infants compared to those in the normal newborn nursery.

Purpose: To determine if a significant difference exists in the bleeding complications following circumcision in neonates admitted to neonatal intensive care unit (NICU) versus the normal newborn nursery (NNN).

Materials And Methods: Observational cohort study of 260 infants undergoing circumcision with Gomco clamp. Vitamin K was given to neonates at delivery.

Sleep During Pregnancy: The nuMoM2b Pregnancy and Sleep Duration and Continuity Study.

Study Objectives: To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables.

Methods: Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy.