Brief Report: Intracellular Cystatin B Levels Are Altered in HIV-Infected Participants With Respect to Neurocognitive Status and Antiretroviral Therapy.

ABSTRACT: With advances in HIV treatment, people with HIV (PWH) are living longer but experience aging-related comorbidities, including cognitive deficits, at higher rates than the general population. Previous studies have shown alterations in lysosomal proteins in blood from PWH with severe dementia. However, these markers have not been evaluated in PWH with milder neurocognitive impairment. We sought to determine whether levels of the lysosomal cysteine protease cathepsin B (CatB) and its endogenous inhibitor cystatin B (CysB) were altered in PWH with neurocognitive impairment and whether antiretroviral therapy (ART) further influenced these levels. Peripheral blood mononuclear cells were obtained from the tenofovir arm of a multicenter clinical trial in which ART-naive, HIV+ participants received treatment for 48 weeks (ACTG A5303, NCT01400412). PWH were divided by neurocognitive status (eg, with or without neurocognitive impairment) before ART initiation. Intracellular levels of CatB and CysB were measured in T cells and monocytes by means of flow cytometry. Levels of CysB were significantly decreased in both CD4 + T cells and CD8 + T cells after 48 weeks of ART in HIV+ participants without neurocognitive impairment but not in participants with neurocognitive impairment. Levels of CysB were increased in CD14 + monocytes from the participants with neurocognitive impairment after ART. Levels of CysB and CatB positively correlated regardless of HIV, neurocognitive status, or exposure to ART. These findings suggest that CysB has the potential to provide mechanistic insight into HIV-associated neurocognitive disorders or provide a molecular target for systemic monitoring or treatment of neurocognitive impairment in the context of ART and should be investigated further.

Changes in lipidomic profile by anti-retroviral treatment regimen: An ACTG 5257 ancillary study.

ABSTRACT: High cardiovascular disease risk in people living with HIV is partly attributed to antiretroviral therapy (ART). Lipid response to ART has been extensively studied, yet, little is known how small molecule lipids respond to Integrase inhibitor-based (INSTI-based) compared to Protease inhibitor-based (PI-based) ART regimens.Ancillary study to a phase 3, randomized, open-label trial [AIDS Clinical Trial Group A5257 Study] in treatment-naive HIV-infected patients randomized in a 1:1:1 ratio to receive ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r) (both PI-based), or raltegravir with Tenofovir Disoproxil Fumarate-TDF plus emtricitabine (RAL, INSTI-based).We examined small molecule lipid response in a subcohort of 75 participants. Lipidomic assays of plasma samples collected pre- and post-ART treatment (48 weeks) were conducted using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. The effect of ART regimens was regressed on lipid species response adjusting for the baseline covariates (lipids, age, sex, race, CD4 level, BMI, and smoking). Results were validated in the Centers for AIDS Research Network of Integrated Clinical Systems study (N = 16).Out of 417 annotated lipids, glycerophospholipids (P = .007) and sphingolipids (P = .028) had a higher response to ATV/r and DRV/r compared to RAL. The lysophosphatidylcholine (LPCs(16:1),(17:1),(20:3)) and phosphophatidylcholine species (PCs(40:7),(38:4)) had an opposite response to RAL versus ATV/r in the discovery and validation cohort. The INSTI-based regimen had an opposite response of ceramide species ((d38:1), (d42:2)), PCs((35:2), (38:4)), phosphatidylethanolamines (PEs(38:4), (38:6)), and sphingomyelin(SMd38:1) species compared with the PI-based regimens. There were no differences observed between 2 PI-based regimens.We observed differences in response of small molecule lipid species by ART regimens in treatment-naive people living with HIV.

Physical activity trends and metabolic health outcomes in people living with HIV in the US, 2008-2015.

Despite its potential to improve metabolic health outcomes, longitudinal physical activity (PA) patterns and their association with cardiometabolic disease among people living with HIV (PLWH) have not been well characterized. We investigated this relationship among PLWH in the Centers for AIDS Research Network of Integrated Clinical Systems with at least one PA self-report between 2008 and 2015. The 4-item Lipid Research Clinics PA instrument was used to categorize habitual PA levels as: Very Low, Low, Moderate, or High. We analyzed demographic differences in PA patterns. Multivariable generalized estimating equation regression models were fit to assess longitudinal associations of PA with blood pressure, lipid, and glucose levels. Logistic regression modeling was used to assess the odds of being diagnosed with obesity, cardiovascular disease (CVD), cerebrovascular disease, hypertension, diabetes, or multimorbidity. A total of 40,462 unique PA assessments were provided by 11,719 participants. Only 13% of PLWH reported High PA, while 68% reported Very Low/Low PA at baseline and did not increase PA levels during the study period. Compared to those reporting High PA, participants with Very Low PA had almost 2-fold increased risk for CVD. Very Low PA was also associated with several risk factors associated with CVD, most notably elevated triglycerides (odds ratio 25.4), obesity (odds ratio 1.9), hypertension (odds ratio 1.4), and diabetes (odds ratio 2.3; all p < 0.01). Low levels of PA over time among PLWH are associated with increased cardiometabolic disease risk.

Obesity Affects the Association of Bioelectrical Impedance Phase Angle With Mortality in People Living With HIV.

Bioelectrical impedance analysis phase angle (BIA-PA) is a valid indicator of mortality risk in people living with HIV; however, it is not known whether BIA-PA is valid for people living with HIV who are overweight or obese. We assessed whether BIA-PA differentially predicted mortality by body mass index category in participants receiving clinical care at a single site between 2000 and 2012. Change in BIA-PA from the highest versus last available phase angle was assessed using multivariate logistic regression models. Eight hundred ninety participants were included in the final analyses, with 102 deaths recorded during the study period. Decline in BIA-PA was associated with mortality in underweight and normal weight participants but not in overweight or obese participants. Additional investigation is warranted to determine the appropriate clinical BIA-PA equations and parameters to identify overweight and obese patients with increased mortality risk.

Low-density lipoprotein cholesterol response after statin initiation among persons living with human immunodeficiency virus.

BACKGROUND: Meta-analyses of general population studies report mean low-density lipoprotein cholesterol (LDL-C) reductions of 30% to <50% with moderate-intensity and ≥50% with high-intensity statins. Persons living with human immunodeficiency virus (PLWH) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet many have elevated LDL-C. OBJECTIVE: To evaluate LDL-C response after statin initiation among PLWH. METHODS: We conducted a retrospective cohort study of PLWH initiating statins between 2009 and 2013 (N = 706). Patients were categorized into mutually exclusive groups in the following hierarchy: history of coronary heart disease (CHD), diabetes, prestatin LDL-C ≥190 mg/dL, 10-year predicted ASCVD risk ≥7.5%, and none of the above (ie, unknown statin indication). The primary outcome was a ≥30% reduction in LDL-C after statin initiation. RESULTS: Among patients initiating statins, 5.8% had a history of CHD, 13.6% had diabetes, 6.2% had LDL-C ≥190 mg/dL, 35.4% had 10-year ASCVD risk ≥7.5%, and 39.0% had an unknown statin indication. Among patients with a history of CHD, 31.7% achieved a ≥30% LDL-C reduction compared with 25.0%, 59.1%, and 33.9% among those with diabetes, LDL-C ≥190 mg/dL, and 10-year ASCVD risk ≥7.5%, respectively. In multivariable adjusted analyses and compared to patients with an unknown statin indication, LDL-C ≥ 190 mg/dL was associated with a prevalence ratio for an LDL-C reduction ≥30% of 1.81 (95% confidence interval, 1.34-2.45), whereas no statistically significant association was present for history of CHD, diabetes, and 10-year ASCVD risk ≥7.5%. CONCLUSION: A low percentage of PLWH achieved the expected reductions in LDL-C after statin initiation, highlighting an unmet need for ASCVD risk reduction.

HIV-1 latent reservoir size and diversity are stable following brief treatment interruption.

BACKGROUND: The effect of a brief analytical treatment interruption (ATI) on the HIV-1 latent reservoir of individuals who initiate antiretroviral therapy (ART) during chronic infection is unknown. METHODS: We evaluated the impact of transient viremia on the latent reservoir in participants who underwent an ATI and at least 6 months of subsequent viral suppression in a clinical trial testing the effect of passive infusion of the broadly neutralizing Ab VRC01 during ATI. RESULTS: Measures of total HIV-1 DNA, cell-associated RNA, and infectious units per million cells (IUPM) (measured by quantitative viral outgrowth assay [QVOA]) were not statistically different before or after ATI. Phylogenetic analyses of HIV-1 env sequences from QVOA and proviral DNA demonstrated little change in the composition of the virus populations comprising the pre- and post-ATI reservoir. Expanded clones were common in both QVOA and proviral DNA sequences. The frequency of clonal populations differed significantly between QVOA viruses, proviral DNA sequences, and the viruses that reactivated in vivo. CONCLUSIONS: The results indicate that transient viremia from ATI does not substantially alter measures of the latent reservoir, that clonal expansion is prevalent within the latent reservoir, and that characterization of latent viruses that can reactivate in vivo remains challenging. TRIAL REGISTRATION: ClinicalTrials.gov NCT02463227FUNDING. Funding was provided by the NIH.

Examining Sexual Function Among Individuals With HIV in a Midwestern US Urban Outpatient Clinic Setting.

The role of sexual function and its impact on HIV management have been inadequately evaluated. A cross-sectional study in 2009 of 202 patients with HIV were recruited to examine sexual function and psychosocial/HIV management factors. Analyses assessed the relationship between sexual function, sociodemographic factors, biomedical markers, and depressive symptomology. The M-Estimator compared differences in the means of the HIV, cancer survivors, and the normative cohorts. More than 75% were on combination antiretroviral therapy, of which 70% had suppressed HIV viral loads. Patients with unsuppressed HIV viral loads reported lower rates of arousal. Better overall health was associated with higher rates of overall sexual function, arousal, and interest. Compared to the normative and cancer survivor cohorts, mean sexual function was significantly lower in the HIV-infected cohort in all subscales, except for masturbation. These findings suggest lower sexual function impacts individuals with HIV in ways related to negative biomedical and psychosocial factors.

Monocyte bioenergetic function is associated with body composition in virologically suppressed HIV-infected women.

Women living with HIV may present with high levels of body fat that are associated with altered bioenergetic function. Excess body fat may therefore exacerbate the bioenergetic dysfunction observed with HIV infection. To determine if body fat is associated with bioenergetic function in HIV, we conducted a cross-sectional study of 42 women with HIV who were virologically suppressed on antiretroviral therapy. Body composition was determined via dual-energy x-ray absorptiometry. Oxygen consumption rate (OCR) of monocytes was sorted from peripheral blood mononuclear cells obtained from participants in the fasting state. Differences in bioenergetic function, as measured by OCR, was assessed using Kruskal-Wallis tests and Spearman correlations adjusted for age, race, and smoking status. Participants were 86% Black, 45.5 years old, 48% current smokers, and 57% were obese (body mass index ≥30). Nearly all women (93%) had >30% total fat mass, while 12% had >50% total fat mass. Elevated levels of total fat mass, trunk fat, and leg fat were inversely correlated with measures of bioenergetic health as evidenced by lower maximal and reserve capacity OCR, and Bioenergetic Health Index. Measures of extracellular acidification (ECAR) in the absence (basal) or maximal (with oligomycin) were positively correlated with measures of bioenergetics, except proton leak, and were negatively correlated with fat mass. Despite virological suppression, women with HIV present with extremely high levels of adiposity that correlate with impaired bioenergetic health. Without effective interventions, this syndemic of HIV infection and obesity will likely have devastating consequences for our patients, potentially mediated through altered mitochondrial and glycolytic function.

Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 Infection.

HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4+ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4+ T cell in HIV-1-infected individuals results in altered humoral responses specific to antigens encountered at mucosal surfaces. Comprehensive protein microarray of systemic humoral responses to intestinal microbiota demonstrated reduced IgG responses to antigens derived from Proteobacteria and Firmicutes but not Bacteroidetes. Importantly, intestinal secretions of antiretroviral therapy-treated HIV-1-infected individuals exhibited a significant elevation of IgM levels and decreased IgA/IgM and IgG/IgM ratios of antibodies specific to a variety of microbial and food antigens. The presented findings indicate reduced competence of mucosal B cells for class switch recombination from IgM to other isotypes limiting their capacity to react to changing antigenic variety in the gut lumen. Decreased availability of microbiota-specific IgA and IgG may be an important factor contributing to the translocation of microbial antigens across the intestinal mucosal barrier and their systemic dissemination that drives chronic inflammation in HIV-1-infected individuals.

Characterizing Failure to Establish Hepatitis C Care of Baby Boomers Diagnosed in the Emergency Department.

BACKGROUND: Emergency departments (EDs) are high-yield sites for hepatitis C virus (HCV) screening, but data regarding linkage to care (LTC) determinants are limited. METHODS: Between September 2013 and June 2014, 4371 baby boomers unaware of their HCV status presented to the University of Alabama at Birmingham ED and underwent opt-out screening. A linkage coordinator facilitated referrals for positive cases. Demographic data, International Classification of Diseases, Ninth Revision codes, and clinic visits were collected, and patients were (retrospectively) followed up until February 2015. Linkage to care was defined as an HCV clinic visit within the hospital system. RESULTS: Overall, 332 baby boomers had reactive HCV antibody and detectable plasma ribonucleic acid. The mean age was 57.3 years (standard deviation = 4.8); 70% were male and 61% were African Americans. Substance abuse (37%) and psychiatric diagnoses (30%) were prevalent; 9% were identified with cirrhosis. During a median follow-up of 433 days (interquartile range, 354-500), 117 (35%) linked to care and 48% needed inpatient care. In multivariable analysis, the odds of LTC failure were significantly higher for white males (adjusted odds ratio [aOR], 2.57; 95% confidence interval [CI], 1.03-6.38) and uninsured individuals (aOR, 5.16; 95% CI, 1.43-18.63) and lower for patients with cirrhosis (aOR, 0.36; 95% CI, 0.14-0.92) and access to primary care (aOR, 0.20; 95% CI, 0.10-0.41). CONCLUSIONS: In this cohort of baby boomers with newly diagnosed HCV in the ED, only 1 in 3 were linked to HCV care. Although awareness of HCV diagnosis remains important, intensive strategies to improve LTC and access to curative therapy for diagnosed individuals are needed.

Incidence and Predictors of Abnormal Anal Cytology Findings Among HIV-Infected Adults Receiving Contemporary Antiretroviral Therapy.

BACKGROUND: Anal cancer rates are higher for human immunodeficiency virus (HIV)-infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor lesions detected by anal cytology. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval [CI], 11.3-16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9-22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6-14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8-15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.01-1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31-4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78-8.54) remained associated with incident abnormalities. CONCLUSIONS: The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.

Psychiatric Diagnoses among an HIV-Infected Outpatient Clinic Population.

As individuals with HIV infection are living longer, the management of psychiatric disorders has increasingly been incorporated into comprehensive care. Individuals were recruited from an outpatient HIV clinic to assess the prevalence and related associations of current psychiatric disorders and biomarkers. Of the 201 participants who completed the interviews, the median age was 43.5 years, and the majority was male and African American. Most were receiving HIV therapy and 78% of those had achieved virologic suppression. Prevalent psychiatric diagnoses included major depressive disorder, generalized anxiety, and agoraphobia. Alcohol and cocaine/crack abuse and dependence were common substance use disorders. Current receipt of HIV therapy was less common among those diagnosed with generalized anxiety disorder. Agoraphobia was the only disorder associated with unsuppressed viral load. Psychiatric and substance use disorders are highly prevalent among an urban HIV clinic population, although we identified few associations between psychiatric diagnoses and HIV diseases status.

Mechanisms Influencing Circadian Blood Pressure Patterns Among Individuals with HIV.

HIV+ individuals have an increased risk for cardiovascular disease (CVD), but the mechanisms behind this association are poorly understood. While hypertension is a well-established CVD risk factor, clinic-based blood pressure (BP) assessment by itself cannot identify several important BP patterns, including white coat hypertension, masked hypertension, nighttime hypertension, and nighttime BP dipping. These BP patterns can be identified over a 24-h period by ambulatory BP monitoring (ABPM). In this review, we provide an overview of the potential value of conducting ABPM in HIV+ individuals. ABPM phenotypes associated with increased CVD risk include masked hypertension (i.e., elevated out-of-clinic BP despite non-elevated clinic BP), nighttime hypertension, and a non-dipping BP pattern (i.e., a drop in BP of <10 % from daytime to nighttime). These adverse ABPM phenotypes may be highly relevant in the setting of HIV infection, given that increased levels of inflammatory biomarkers, high psychosocial burden, high prevalence of sleep disturbance, and autonomic dysfunction have been commonly reported in HIV+ persons. Additionally, although antiretroviral therapy (ART) is associated with lower AIDS-related morbidity and CVD risk, the mitochondrial toxicity, oxidative stress, lipodystrophy, and insulin resistance associated with long-term ART use potentially lead to adverse ABPM phenotypes. Existing data on ABPM phenotypes in the setting of HIV are limited, but suggest an increased prevalence of a non-dipping BP pattern. In conclusion, identifying ABPM phenotypes may provide crucial information regarding the mechanisms underlying the excess CVD risk in HIV+ individuals.

Maternal post-absorptive leucine kinetics during late pregnancy in US women with HIV taking antiretroviral therapy: a cross-sectional pilot study.

BACKGROUND: Despite the success of combination antiretroviral therapy (cART) for the prevention of mother to child transmission of HIV, infants exposed to cART in utero frequently are born smaller and have mild cardiac abnormalities. The mechanisms responsible for lower birth weight and cardiac abnormalities in children exposed to cART are unclear but could be related to dysregulation of maternal amino acid metabolism during pregnancy. Previous data in HIV(-) women have shown a relationship between abnormal maternal protein metabolism during pregnancy and low infant birth weight and animal data demonstrate a relationship between altered maternal protein metabolism and increased risk for offspring cardiovascular abnormalities. OBJECTIVE: The objectives of this study were to: characterize post-absorptive maternal leucine kinetics during late pregnancy andexamine the relationships between maternal leucine kinetics and offspring birth weight and cardiac function. DESIGN: Post-absorptive maternal leucine kinetics (evaluated by using stable isotope tracer methodology) in 16 HIV(+) women receiving cART and 14 HIV(-) US women during the 3rd trimester of pregnancy were compared. Relationships between post-absorptive maternal leucine kinetics, cardiac function (echocardiography) and birth weight were statistically examined. RESULTS: Maternal plasma leucine concentration (HIV(-): 82.8 ± 10.7 vs. HIV(+): 72.3 ± 13.5 µM, p=0.06) and leucine oxidation rate (HIV(-): 6.1 ± 1.6 vs. HIV(+): 4.9 ± 1.8 µmol/kgBW/min, p=0.03) were lower in HIV+ women compared to controls. Total leucine turnover rate, non-oxidative leucine disposal rate and post-absorptive maternal glucose and palmitate kinetics did not differ between groups. Left ventricular fractional shortening tended to be lower in children born to HIV(+) compared to controls (HIV(-): 42 ± 1 vs. HIV+: 36 ± 5 %, p=0.08) and associated with lower maternal plasma leucine concentration (r= 0.43, p=0.08). CONCLUSIONS: Preliminary results indicate that post-absorptive maternal leucine metabolism during late pregnancy is mildly altered in HIV+ US women taking cART. The clinical significance of maternal leucine metabolism on adverse infant outcomes is unclear and should be further explored in more expansive studies.

Obesity is associated with race/sex disparities in diabetes and hypertension prevalence, but not cardiovascular disease, among HIV-infected adults.

Race/sex differences are observed in cardiometabolic disease (CMD) risk and prevalence in the context of treated, chronic HIV infection, and these differences could be exacerbated by disparities in obesity prevalence. We sought to determine the effect of obesity on these disparities among people living with HIV. Prevalence of CMD (dyslipidemia, cardiovascular disorders, hypertension, diabetes, chronic kidney disease) was determined for patients seen at the University of Alabama at Birmingham HIV clinic between 7/2010 and 6/2011. Staged logistic regression was used to examine the impact of race/sex on comorbidities adjusting for key confounders including/excluding obesity (body mass index ≥30 kg/m(2)). Of 1,800 participants, 77% were male, 54% were black, and 25% were obese. Obesity prevalence differed by race/sex: black women 49%, black men 24%, white women 24%, white men 15% (p<0.01). Compared to white men, other groups had reduced odds for dyslipidemia and cardiovascular disorders (p<0.01). Black men had increased odds for hypertension and chronic kidney disease, while black women had a nearly 2-fold increased odds for diabetes and hypertension (all at p<0.01). The associations of black women with diabetes and hypertension were attenuated when obesity was included in the models. Other group differences remained significant. Disparities in obesity prevalence do not explain race/sex differences in all CMD among people with HIV. Obesity accounted for associations with diabetes/hypertension for black women, who may benefit from weight reduction to decrease disease risk. Further investigations into the etiology and treatment of CMD in people living with HIV should consider unique race/sex treatment issues.

Inhibition of the lymphocyte metabolic switch by the oxidative burst of human neutrophils.

Activation of the phagocytic NADPH oxidase-2 (NOX-2) in neutrophils is a critical process in the innate immune system and is associated with elevated local concentrations of superoxide, hydrogen peroxide (H2O2) and hypochlorous acid. Under pathological conditions, NOX-2 activity has been implicated in the development of autoimmunity, indicating a role in modulating lymphocyte effector function. Notably, T-cell clonal expansion and subsequent cytokine production requires a metabolic switch from mitochondrial respiration to aerobic glycolysis. Previous studies demonstrate that H2O2 generated from activated neutrophils suppresses lymphocyte activation but the mechanism is unknown. We hypothesized that activated neutrophils would prevent the metabolic switch and suppress the effector functions of T-cells through a H2O2-dependent mechanism. To test this, we developed a model co-culture system using freshly isolated neutrophils and lymphocytes from healthy human donors. Extracellular flux analysis was used to assess mitochondrial and glycolytic activity and FACS analysis to assess immune function. The neutrophil oxidative burst significantly inhibited the induction of lymphocyte aerobic glycolysis, caused inhibition of oxidative phosphorylation and suppressed lymphocyte activation through a H2O2-dependent mechanism. Hydrogen peroxide and a redox cycling agent, DMNQ, were used to confirm the impact of H2O2 on lymphocyte bioenergetics. In summary, we have shown that the lymphocyte metabolic switch from mitochondrial respiration to glycolysis is prevented by the oxidative burst of neutrophils. This direct inhibition of the metabolic switch is then a likely mechanism underlying the neutrophil-dependent suppression of T-cell effector function.

Parks as a tool for HIV management.

Access to parks improves overall health outcomes in the general population. Given that HIV infection has become a chronic disease to manage, among populations engaged in medical care, parks may be promoted as physical activity opportunities in order to manage chronic comorbid conditions. We conducted a cross-sectional examination of the relationships between sociodemographic and biomedical characteristics to park proximity among 635 individuals receiving outpatient HIV care. The data collected included HIV-related biomarkers, depression, and diagnoses of other chronic diseases. The total acres of parks an individual is exposed within one-quarter mile from their home were assessed. The cohort included 635 individuals (67% men, 73% black, and 21% white, mean age 42 years). Unemployment was negatively associated with park availability. Park proximity was not associated with depression or HIV biomarkers. As yet, little effort has been committed to promoting park usage as a low-cost, sustainable method to addressing comorbidities among individuals with HIV.

Persistent HIV-related stigma among an outpatient US clinic population.

Despite advancements in the public's understanding of HIV infection, felt stigma towards individuals living with HIV persists. Stigma has been associated with adverse health outcomes, including poor adherence to care, and increased participation in HIV transmission risk behaviours. We evaluated the level of felt stigma and its relationship to other psychosocial and medical factors among a sample of 201 individuals with HIV engaged in care. The overall mean stigma score, as measured by the Reece Stigma Scale, was 21.7 (SD 8.7). In univariate analysis, felt stigma scores were higher among women, African Americans, younger participants, and individuals with less education. Higher felt stigma scores were also found among individuals who reported having fair to poor overall health, moderate to severe symptoms of depression and anxiety, and those with a current diagnosis of alcohol dependence, generalised anxiety disorder, agoraphobia, pain disorder, and current smokers. Higher felt stigma scores were independently associated with individuals with anxiety symptoms. These analyses highlight that stigma persists among individuals with HIV and may play an important role in HIV care. The relationship between psychiatric disorders and psychosocial factors highlights an opportunity to develop interventions that will address these common comorbidities and reduce stigma.

Current practices of screening for incident hepatitis C virus (HCV) infection among HIV-infected, HCV-uninfected individuals in primary care.

BACKGROUND: Human immunodeficiency virus (HIV)-infected, hepatitis C virus (HCV)-uninfected patients are at risk for incident HCV infection, but little is known about screening practices for incident HCV among HIV-infected individuals in HIV primary care clinics. METHODS: We used data from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) to investigate historical trends in screening for incident HCV infection among HIV-infected patients who were HCV-uninfected at enrollment in care. We used descriptive measures and Poisson regression to identify factors associated with screening for HCV infection (using HCV antibody or RNA), performed temporal analyses to assess changes in screening over time, and investigated the frequency with which elevated alanine aminotransferase (ALT) levels were followed by diagnostic HCV testing. RESULTS: Among 17 090 patients registered at CNICS sites between 2000 and 2011, 14 534 (85%) received HCV antibody screening within 3 months of enrolling in care, and 9077 met all of the inclusion criteria. Only 55.6% ever received additional HCV screening. HCV screening increased over time, but not uniformly at all sites. Only 26.7% of first-time ALT elevations to >100 IU/L were followed up within 12 months by HCV antibody or RNA testing. CONCLUSIONS: Although most HIV-infected patients were screened for prevalent HCV infection at enrollment in care, only half who were HCV uninfected were screened again. Screening varied between sites, even when controlling for demographics and risk behaviors. Patients with new ALT elevations to >100 IU/L were seldom assessed for incident HCV infection. Guidelines are needed to help HIV providers know whom to screen, how frequently to screen, and which screening test to use.

Bone alterations associated with HIV.

HIV infection and initiation of antiretroviral therapy (ART) have been consistently associated with decreased bone mineral density (BMD), with growing evidence linking HIV to an increased risk of fracture. This is especially concerning with the expanding number of older persons living with HIV. Interestingly, recent data suggest that HIV-infected children and youth fail to achieve peak BMD, possibly increasing their lifetime risk of fracture. Elucidating the causes of the bone changes in HIV-positive persons is challenging because of the multifactorial nature of bone disease in HIV, including contribution of the virus, immunosuppression, ART toxicity, and traditional osteoporosis risk factors, such as age, lower weight, tobacco, and alcohol use. Thus, practitioners must recognize the risk of low BMD and fractures and appropriately screen patients for osteoporosis if risk factors exist. If fractures do occur or elevated fracture risk is detected through screening, treatment with bisphosphonate medications appears safe and effective in the HIV+population.