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.

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.

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.

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.

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.

Metabolic consequences of HIV: pathogenic insights.

With the advances in antiretroviral therapy (ART), HIV infection has been transformed into a chronic medical condition that can be effectively managed like diabetes or hypertension. For HIV care providers, the focus of care for many patients has shifted from prevention of opportunistic infection and AIDS-related conditions to age-related cardiometabolic comorbidities, including cardiovascular disease, diabetes, obesity, and frailty. Numerous reports have highlighted that these diseases are occurring at an earlier age among HIV-infected persons. However, there is an ongoing debate regarding the role of HIV infection, ART, and other factors that may underlie the accelerated occurrence of these diseases. Herein, we review the epidemiology of the US HIV epidemic with regards to several metabolic comorbidities and address mechanisms that likely contribute to the current nature of HIV disease.

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.

Improving cervical cancer screening rates in an urban HIV clinic.

Human immunodeficiency virus (HIV)-infected women are at increased risk of invasive cervical cancer; however, screening rates remain low. The objectives of this study were to analyze a quality improvement intervention to increase cervical cancer screening rates in an urban academic HIV clinic and to identify factors associated with inadequate screening. Barriers to screening were identified by a multidisciplinary quality improvement committee at the Washington University Infectious Diseases clinic. Several strategies were developed to address these barriers. The years pre- and post-implementation were analyzed to examine the clinical impact of the intervention. A total of 422 women were seen in both the pre-implementation and post-implementation periods. In the pre-implementation period, 222 women (53%) underwent cervical cancer screening in the form of Papanicolaou (Pap) testing. In the post-implementation period, 318 women (75.3%) underwent cervical cancer screening (p < 0.01). Factors associated with lack of screening included fewer visits attended (pre: 4.2 ± 1.5; post: 3.4 ± 1.4; p < 0.01). A multidisciplinary quality improvement intervention was successful in overcoming barriers and increasing cervical cancer screening rates in an urban academic HIV clinic.

Pilot study of pioglitazone and exercise training effects on basal myocardial substrate metabolism and left ventricular function in HIV-positive individuals with metabolic complications.

BACKGROUND: Individuals with HIV infection and peripheral metabolic complications have impaired basal myocardial insulin sensitivity that is related to left ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown to be effective in improving peripheral insulin sensitivity can improve basal myocardial insulin sensitivity and diastolic function in people with HIV and peripheral metabolic complications. OBJECTIVE: In a pilot study, we evaluated whether the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist pioglitazone or combined endurance and resistance exercise training improves basal myocardial insulin sensitivity and diastolic function in HIV+ adults with peripheral metabolic complications. DESIGN: Twenty-four HIV+ adults with metabolic complications including peripheral insulin resistance were randomly assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive endurance and resistance exercise training (EXS; 90-120 min/d, 3 d/wk). Basal myocardial substrate metabolism was quantified by radioisotope tracer methodology and positron emission tomography (PET) imaging, and LV function was measured by echocardiography. RESULTS: Twenty participants completed the study. Neither PIO nor EXS resulted in a detectable improvement in basal myocardial insulin sensitivity or diastolic function. Post hoc analyses revealed sample sizes of more than 100 participants are needed to detect significant effects of these interventions on basal myocardial insulin sensitivity and function. CONCLUSIONS: PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications.

Pain is independently associated with impaired physical function in HIV-infected patients.

INTRODUCTION: Human immunodeficiency virus (HIV)-infected patients in the current treatment era can achieve normal life expectancies but experience a high degree of medical and psychiatric comorbidity. Impaired physical function and pain, often in the context of mood disorders and substance abuse, are common in HIV-infected patients. The objective of this study was to investigate the relationship of pain, a modifiable condition, to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse. METHODS: Participants in a prospective cohort of HIV-infected patients at the University of Alabama at Birmingham were included. Patient-reported outcome measures were used to cross-sectionally assess pain and physical function (EuroQOL), mood disorders (PHQ), and substance abuse (ASSIST). Univariate and multivariable models were built with pain as the principal independent variable of interest and three domains of physical function (mobility, self-care, and usual activities) as outcomes. Covariates included mood, substance abuse, age, race, sex, insurance status, HIV transmission risk factor, and CD4+ T-cell count. RESULTS: Among 1,903 participants, 693 (37%) reported pain; 509 (27%) had a mood disorder; and 157 (8.4%) reported current substance abuse. In multivariable models, pain was independently associated with increased odds of impairment in all three domains of physical function investigated-mobility (aOR 10.5, 95% CI 7.6-14.6), self-care (aOR 4.1, 95% CI 2.2-7.4), and usual activities (aOR 5.4, 95% CI 4.0-7.4). DISCUSSION: Pain was associated with substantially increased odds of impairment in physical function. Pain should be an important consideration in HIV primary care. Interventions to address pain and impaired physical function should be investigated.

Urban farming: a non-traditional intervention for HIV-related distress.

As individuals with HIV are living longer with less morbidity, developing interventions that address co-morbidities are essential. Psychological distress symptoms fluctuate throughout HIV infection and interrupt self-care practices. This pilot study was conducted to test the implementation of a clinic-recruited sample to participate in a community-based urban farming intervention, and assess the efficacy of reducing psychological distress symptoms. While the changes were not statistically significant, participants reported less distress symptoms, improved overall general health, and reduced frequency of illicit drug use. These findings support the development of a larger scale study to examine the impact of this nontraditional intervention.

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.

Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D Levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population.

BACKGROUND: we explored serum 25-hydroxyvitamin D (25[OH]D) levels and associated factors for insufficiency or deficiency in an adult human immunodeficiency virus (HIV) cohort and compared 25(OH)D levels with those in the general US population. METHODS: using baseline data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN), a prospective, observational cohort study of HIV-infected adults enrolled at 7 HIV specialty clinics in 4 US cities from March 2004 to June 2006, we estimated the prevalence of vitamin D insufficiency or deficiency (defined as 25(OH)D levels <30 ng/mL), standardized by age, race, and sex. Using multiple logistic regression, we examined risk factors for vitamin D insufficiency or deficiency. RESULTS: among 672 SUN participants with baseline serum 25(OH)D determinations who were not receiving vitamin D supplements, 70.3% (95% confidence interval [CI], 68.1%-74.9%) were vitamin D insufficient or deficient, compared with 79.1% (95% CI, 76.7-81.3) of US adults. Factors associated with vitamin D insufficiency or deficiency included black race (adjusted odds ratio [aOR], 4.51; 95% CI, 2.59-7.85), Hispanic ethnicity (aOR, 2.78; 95% CI, 1.31-5.90), higher body mass index (aOR, 1.04; 95% CI, 1.00-1.09), hypertension (aOR, 1.88; 95% CI, 1.10-3.22), lack of exercise (aOR, 3.14; 95% CI, 1.80-5.47), exposure to efavirenz (aOR, 1.98; 95% CI, 1.18-3.34), higher exposure to ultraviolet light (aOR, .78; 95% CI, .71-.86), renal insufficiency (aOR, .55; 95% CI, .36-.83), and exposure to ritonavir (aOR, .56; 95% CI, .35-0.89). CONCLUSIONS: similar to findings in US adults generally, vitamin D insufficiency or deficiency is highly prevalent among HIV-infected adults and is associated with known risk factors. Observed associations of vitamin D levels with renal insufficiency and with use of ritonavir- and efavirenz-containing regimens are consistent with both HIV-related and therapy-mediated alterations in vitamin D metabolism. Clinicians should consider screening all patients for vitamin D insufficiency or deficiency.

Progression of carotid intima-media thickness in a contemporary human immunodeficiency virus cohort.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at risk for premature cardiovascular disease (CVD). Predictors of atherosclerotic disease progression in contemporary patients have not been well described. METHODS: Using data from a prospective observational cohort of adults infected with HIV (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy), we assessed common carotid artery intima-media thickness (CIMT) at baseline and year 2 by ultrasound. We examined HIV-associated predictors of CIMT progression after adjusting for age, sex, race/ethnicity, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol level, and baseline CIMT using linear regression. RESULTS: Among 389 participants (median age at baseline, 42 years; male sex, 77%; median CD4+ cell count at baseline, 485 cells/mm³; 78% receiving antiretroviral therapy), the median 2-year CIMT change was 0.016 mm (interquartile range, -0.003 to 0.033 mm; P < .001). Lesser CIMT progression was associated with a suppressed viral load at baseline (-0.009 mm change; P = .015) and remaining virologically suppressed throughout follow-up (-0.011 mm change; P < .001). After adjusting for additional risk factors and a suppressed viral load during follow-up, nonnucleoside reverse transcriptase inhibitor versus protease inhibitor exposure was associated with lesser CIMT progression (-0.011 mm change; P = .02). CONCLUSIONS: Suppressing HIV replication below clinical thresholds was associated with less progression of atherosclerosis. The proatherogenic mechanisms of HIV replication and the net CVD benefit of different antiretroviral drugs should be a focus of future research.

High Prevalence of Echocardiographic Abnormalities among HIV-infected Persons in the Era of Highly Active Antiretroviral Therapy.

BACKGROUND: in the era of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected persons have higher cardiovascular disease risk. Little is known about asymptomatic abnormalities in cardiac structure and function in this population. METHODS: the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) is a prospective, observational, multi-site cohort of 656 HIV-infected participants who underwent baseline echocardiography during 2004-2006. We examined prevalence of and factors associated with left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary hypertension (PHTN), left ventricular hypertrophy (LVH), and left atrial enlargement (LAE). RESULTS: participant characteristics were as follows: median age, 41 years; 24% women; 29% non-Hispanic black; 73% receiving HAART; and median CD4+ cell count, 462 cells/µL. Among evaluable participants, 18% had LVSD, 26% had DD, 57% had PHTN (right ventricular pressure >30 mm Hg), 6.5% had LVH, and 40% had LAE. In multivariate analyses, significant factors (P < .05) associated with LVSD were history of MI, elevated highly sensitive C-reactive protein (hsCRP) level, and current tobacco smoking; for DD, elevated hsCRP level and hypertension; for PHTN, current use of ritonavir; for LVH, hypertension, diabetes, non-white race, female sex with elevated body mass index, calculated as the weight in kilograms divided by the square of height in meters, of ≥ 25, elevated hsCRP level, and current use of abacavir; for LAE, hypertension and recent marijuana use. CONCLUSIONS: in this large contemporary HIV cohort, the prevalence of subclinical functional and structural cardiac abnormalities was greater than expected for age. Abnormalities were mostly associated with expected and often modifiable risks. Lifestyle modification should become a greater priority in the management of chronic HIV disease.

Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity.

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4 mo of pioglitazone (30 mg/day) with or without supervised, progressive aerobic, and resistance exercise training (1.5-2 h/day, 3 days/wk). The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity. Thirty-nine participants completed the study. Hepatic insulin sensitivity improved similarly in both groups. Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity. Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration. We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Pioglitazone alone did not significantly increase limb adipose content. Potential cardiovascular benefits of these interventions in HIV need investigation.

Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis.

BACKGROUND: In the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC. METHODS: Prospective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography. RESULTS: Myocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/µU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/µU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001). CONCLUSION: Men with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin. TRIAL REGISTRATION: NIH Clinical Trials NCT00656851.

Alcohol consumption is associated with poor health in HIV clinic patient population: a behavioral surveillance study.

Previous research reports that populations with HIV consume higher rates of alcohol than general population. This cross-sectional study (n = 391) was conducted to measure alcohol consumption, factors associated with consumption, and the relationship between alcohol and HIV viral loads among individuals receiving HIV care. Increased alcohol consumption was associated with being male, lower education attainment, and lacking a current HAART prescription. Additionally, among those currently on HAART, unsuppressed viremia was associated with higher levels of alcohol consumption. These findings suggest that there may be a relatively low level of alcohol consumption that is detrimental to virologic suppression among populations with HIV.

Factors associated with non-adherence to antiretroviral therapy in the SUN study.

BACKGROUND: Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality. METHODS: We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire. RESULTS: Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm(3)), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20-3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14-3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18-3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02-2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25-3.57). CONCLUSION: Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.

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.