David B. Hanna

Clostridium difficile infection after adult autologous stem cell transplantation: a multicenter study of epidemiology and risk factors.

We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto-HSCT) within the first year after HSCT in centers with variable epidemiology of hypertoxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto-HSCT recipients at Johns Hopkins Hospital (JHH) and Hôpital Maisonneuve-Rosemont (HMR) between January 2003 and December 2008. Despite center differences in the prevalence of NAP-1 strains during the study period (21% to 43% at JHH versus 80% to 84% in HMR), the 1-year incidence of CDI was similar in the 2 hospitals (6.2% at JHH versus 5.7% at HMR). The median time to infection was 11 days (interquartile range, 1 to 27 days). In case-control analyses, grade ≥2 mucositis (odds ratio [OR], 3.00; P = .02) and receipt of a fourth-generation cephalosporin (OR, 2.76; P = .04) were identified as predictors for CDI. Mucositis was the strongest predictor of risk for CDI in multivariate analysis (adjusted OR, 2.77; P = .03). CDI is a common and early complication of auto-HSCT. Treatment-related gastrointestinal mucosal damage, along with the potentially modifiable risk of antimicrobial exposure, influence the risk for CDI early after auto-HSCT.

Foreign-Born Persons Diagnosed with HIV: Where are They From and Where Were They Infected?

We sought to calculate rates of HIV diagnoses by area of birth among foreign-born persons in a high-incidence US city with many immigrants, and determine probable place of HIV acquisition. Data from the New York City HIV surveillance registry and American Community Survey were used to calculate HIV diagnosis rates by area of birth and determine probable place of HIV acquisition among foreign-born diagnosed in 2006–2012. HIV diagnosis rates varied by area of birth and were highest among African-born persons; absolute numbers were highest among Caribbean-born persons. Probable place of acquisition was a foreign country for 23xa0% (from 9xa0% among Middle Easterners to 43xa0% among Africans), US for 61xa0% (from 34xa0% among Africans to 76xa0% among South Americans), and not possible to estimate for 16xa0%. HIV prevention and testing initiatives should take into account variability by foreign area of birth in HIV diagnosis rates and place of acquisition.ResumenIntentamos calcular los niveles de diagnósticos de VIH por lugar de nacimiento entre personas nacidas en el extranjero en una ciudad de los Estados Unidos de alta incidencia de infección del VIH y con muchos inmigrantes, y determinar el lugar probable de contagio. Se utilizaron los datos del registro de vigilancia del VIH de la ciudad de Nueva York y los datos de la Encuesta de la Comunidad Estadounidense para calcular los niveles de diagnóstico de VIH por lugar de nacimiento y determinar el lugar probable de contagio entre las personas nacidas en el extranjero y diagnosticadas durante el periodo del 2006 al 2012. Los niveles de diagnóstico del VIH variaron por lugar de nacimiento y fueron más altos entre personas de origen africano; los números absolutos fueron más altos entre personas de origen caribeño. El lugar probable de contagio del VIH fue para el 23xa0% otro país (de 9xa0% entre personas del Medio Oriente hasta 43xa0% entre personas de origen africano), para el 61xa0% los Estados Unidos (de 34xa0% entre personas de origen africano hasta 76xa0% entre sudamericanos), y para el 16xa0% no fue posible estimar. Las iniciativas de prevención del VIHxa0y promoción de la prueba del VIH deben tomar en cuenta la variedad porxa0lugar de nacimiento en los niveles de diagnóstico del VIH y el lugar de contagio.

Recent Insights Into Cardiovascular Disease (CVD) Risk Among HIV-Infected Adults.

While mortality rates related to cardiovascular disease (CVD) have decreased over time among adults with HIV, excess risk of CVD in the HIV-infected population may persist despite highly active antiretroviral therapy (HAART) treatment and aggressive CVD risk factor control. Beyond atherosclerotic CVD, recent studies suggest that HIV infection may be associated with left ventricular systolic and diastolic function, interstitial myocardial fibrosis, and increased cardiac fat infiltration. Thus, with the increasing average age of the HIV-infected population, heart failure and arrhythmic disorders may soon rival coronary artery disease as the most prevalent forms of CVD. Finally, the question of whether HIV infection should be considered in clinical risk stratification has never been resolved, and this question has assumed new importance with recent changes to lipid treatment guidelines for prevention of CVD.

HIV diagnosis and utilisation of HIV-related medical care among foreign-born persons in New York City, 2001-2009.

Objectives To measure trends in HIV diagnoses among foreign-born (FB) New Yorkers and compare the epidemic in FB with that in non-FB (NFB). Methods New York City (NYC) HIV/AIDS surveillance registry data were used to measure trends in HIV diagnoses in 2001–2009, calculate HIV diagnosis rates by area of birth, and compare demographic and care characteristics of FB and NFB diagnosed in 2006–2009. The registry contains data on all New Yorkers diagnosed with HIV infection, HIV disease and AIDS, and receives laboratory results on all New Yorkers living with HIV/AIDS. Results From 2001 to 2009, new HIV diagnoses among FB increased modestly in number but significantly as a percent of all cases (17% in 2001 to 28% in 2009; p<0.01). In 2006–2009, the annual rate of diagnosis was lower among FB than NFB (37 vs 56 per 100u2005000). Compared with NFB, FB persons were significantly more likely to be diagnosed concurrently with AIDS; FB had a lower median CD4 count at initiation of care. FB persons were less likely to have insurance, and 13% needed language interpretation services. Conclusions The percentage of HIV diagnoses in NYC attributed to FB persons has increased. HIV infection may remain undiagnosed longer in FB than NFB. FB may benefit from targeted prevention outreach and other services.

Sex-Specific Prediction Models for Sleep Apnea From the Hispanic Community Health Study/Study of Latinos

OBJECTIVEnWe developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects.nnnMETHODSnCross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea indexxa0≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered.nnnRESULTSnA total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea indexxa0≥ 15 events per hour) was 6.1%xa0in female subjects and 13.5%xa0in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie,xa0age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SAxa0risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html).nnnCONCLUSIONSnWe created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects.

Comparing measures of overall and central obesity in relation to cardiometabolic risk factors among US Hispanic/Latino adults

US Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos.

Elevated NT-Pro-Brain Natriuretic Peptide Level Is Independently Associated with All-Cause Mortality in HIV-Infected Women in the Early and Recent HAART Eras in the Women’s Interagency HIV Study Cohort

Background HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women. Design Prospective cohort study. Methods and Results We measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women’s Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3–2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4–5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women. Conclusion NT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.

Emerging from the database shadows: characterizing undocumented immigrants in a large cohort of HIV-infected persons

ABSTRACT Little is known about how HIV affects undocumented immigrants despite social and structural factors that may place them at risk of poor HIV outcomes. Our understanding of the clinical epidemiology of HIV-infected undocumented immigrants is limited by the challenges of determining undocumented immigration status in large data sets. We developed an algorithm to predict undocumented status using social security number (SSN) and insurance data. We retrospectively applied this algorithm to a cohort of HIV-infected adults receiving care at a large urban healthcare system who attended at least one HIV-related outpatient visit from 1997 to 2013, classifying patients as “screened undocumented” or “documented”. We then reviewed the medical records of screened undocumented patients, classifying those whose records contained evidence of undocumented status as “undocumented per medical chart” (charted undocumented). Bivariate measures of association were used to identify demographic and clinical characteristics associated with undocumented immigrant status. Of 7593 patients, 205 (2.7%) were classified as undocumented by the algorithm. Compared to documented patients, undocumented patients were younger at entry to care (mean 38.5 years vs. 40.6 years, pu2009<u20090.05), less likely to be female (33.2% vs. 43.1%, pu2009<u20090.01), less likely to report injection drug use as their primary HIV risk factor (3.4% vs. 18.0%, pu2009<u20090.001), and had lower median CD4 count at entry to care (288 vs. 339u2005cells/mm3, pu2009<u20090.01). After medical record review, we re-classified 104 patients (50.7%) as charted undocumented. Demographic and clinical characteristics of charted undocumented did not differ substantially from screened undocumented. Our algorithm allowed us to identify and clinically characterize undocumented immigrants within an HIV-infected population, though it overestimated the prevalence of patients who were undocumented.

Plasma tryptophan-kynurenine metabolites are altered in human immunodeficiency virus infection and associated with progression of carotid artery atherosclerosis

BackgroundnIt is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals.nnnMethodsnPlasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV-) from the Womens Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque.nnnResultsnAfter a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P < .001), higher KYNA/TRP (P = .01), and similar kynurenic acid levels (P = .51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P < .001), while each SD increment in kynurenic acid (P = .02) and KYNA/TRP (P < .001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant.nnnConclusionsnPlasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

Regulatory CD4+ T Cells Recognize MHC-II-Restricted Peptide Epitopes of Apolipoprotein B

Background: CD4+ T cells play an important role in atherosclerosis, but their antigen specificity is poorly understood. Immunization with apolipoprotein B (ApoB, core protein of low density lipoprotein) is known to be atheroprotective in animal models. Here, we report on a human APOB peptide, p18, that is sequence-identical in mouse ApoB and binds to both mouse and human major histocompatibility complex class II molecules. Methods: We constructed p18 tetramers to detect human and mouse APOB-specific T cells and assayed their phenotype by flow cytometry including CD4 lineage transcription factors, intracellular cytokines, and T cell receptor activation. Apolipoprotein E–deficient (Apoe−/−) mice were vaccinated with p18 peptide or adjuvants alone, and atherosclerotic burden in the aorta was determined. Results: In human peripheral blood mononuclear cells from donors without cardiovascular disease, p18 specific CD4+ T cells detected by a new human leukocyte antigen-antigen D related-p18 tetramers were mostly Foxp3+ regulatory T cells (Tregs). Donors with subclinical cardiovascular disease as detected by carotid artery ultrasound had Tregs coexpressing retinoic acid-related orphan receptor gamma t or T-bet, which were both almost absent in donors without cardiovascular disease. In Apoe−/− mice, immunization with p18 induced Tregs and reduced atherosclerotic lesions. After peptide restimulation, responding CD4+ T cells identified by Nur77-GFP (green fluorescent protein) were highly enriched in Tregs. A new mouse I-Ab-p18 tetramer identified the expansion of p18-specific CD4+ T cells on vaccination, which were enriched for interleukin-10–producing Tregs. Conclusions: These findings show that APOB p18–specific CD4+ T cells are mainly Tregs in healthy donors, but coexpress other CD4 lineage transcription factors in donors with subclinical cardiovascular disease. This study identifies ApoB peptide 18 as the first Treg epitope in human and mouse atherosclerosis.