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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.

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.

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 {"type":"clinical-trial","attrs":{"text":"NCT02463227","term_id":"NCT02463227"}}NCT02463227 FUNDING. Funding was provided by the NIH.

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&nbsp

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.

Despite successful viral control, HIV-1-infected individuals have a higher risk of developing life-threatening comorbidities including liver and cardiovascular diseases which are associated with inflammation and immune dysregulation. However, the specific mediators driving these pathologies are not yet understood. Neutrophils are increasingly recognized as a heterogeneous population with critical roles in immune regulation and disease pathogenesis. Methods of neutrophil characterization developed in our laboratory have facilitated the identification of novel neutrophil subpopulations including two subsets of low-density neutrophils (LDNs). LDNs are known to be expanded in inflammatory conditions including cancers and chronic infections. The LDN subpopulations identified in our laboratory represent different maturation states as indicated by their distinct nuclear morphologies and phenotypic differences [mature (mLDNs) CD16+CD64Low and immature (imLNDs) CD16−CD64+]. Our findings indicate that imLDNs have a reduced capacity for reactive oxygen species production and phagocytosis. We present data demonstrating that HIV-1/AIDS is associated with a higher frequency of imLDNs and significant alterations in total neutrophil phenotype (decreased CD16 and increased CXCR4 and CD10), function, and metabolism including increased expression of genes related to oxidative phosphorylation and mTOR signaling. Observed changes in neutrophil populations correlate with key clinical parameters including CD4+ T cell count, level of liver fibrosis, and arterial stiffness suggesting an important role for these cells and specific subsets in the pathogenesis of HIV-1/AIDS and potentially other inflammatory diseases.

Author(s): Conley, Lois J; Bush, Timothy J; Darragh, Teresa M; Palefsky, Joel M; Unger, Elizabeth R; Patel, Pragna; Steinau, Martin; Kojic, E Milu; Martin, Harold; Overton, E Turner; Cu-Uvin, Susan; Hammer, John; Henry, Keith; Wood, Kathleen; Brooks, John T; SUN Study Group | Abstract: BackgroundAnal 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.MethodsThe 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.ResultsAmong 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.ConclusionsThe incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.

Summary 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: 1) characterize post-absorptive maternal leucine kinetics during late pregnancy and 2) examine 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.

Activation of the phagocytic NADPH oxidase (NOX-2) in neutrophils is a critical process in the innate immune system and is associated with elevated local concentrations of superoxide, hydrogen peroxide 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 hydrogen peroxide 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 hydrogen peroxide-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 hydrogen peroxide-dependent mechanism. The impact of hydrogen peroxide on bioenergetics in the lymphocytes was confirmed using authentic reagent and a redox cycling agent. 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.

BackgroundMeta-analyses of general population studies report mean low-density lipoprotein cholesterol (LDL-C) reductions of 30% to

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.

Despite advancements in the public’s understanding of HIV infection, stigma towards individuals living with HIV persists. Stigma has been associated with adverse health outcomes, including diminished engagement in care, poor medication adherence, and increased participation in HIV transmission risk behaviors. We evaluated the level of perceived stigma and its relationship to other psychosocial and medical factors among a sample of 201 individuals with HIV engaged in care. The Reece Stigma Scale was utilized to determine the level of felt stigma experienced by participants, with stigma scores ranging from 0 (no perceived stigma) to 45 (high perceived stigma). The overall mean stigma score was 21.7 (SD 8.7, range 9–45). In univariate analysis, stigma scores were higher among women, African Americans, younger participants, and individuals with less education. Higher 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, GAD, agoraphobia, pain disorder, and current smokers (p < 0.05 for all). After controlling for significant factors in univariate analyses, higher stigma scores were independently associated with individuals with anxiety symptoms (p< 0.001) and heterosexual individuals (p < 0.05). 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 reduce both stigma and these common comorbidities.

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.

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.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.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.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.PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications.

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.

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., Author Summary Despite significant effort, our understanding of how HIV-1 virus undermines the immune system is limited. HIV-1infection is characterized by extensive damage to intestinal mucosal barrier and translocation of bacteria and microbial products into the systemic circulation. Immune activation induced by microbial products results in chronic inflammation that drives HIV-1 pathogenesis and progression to AIDS despite successful control of HIV-1 replication by antiretroviral therapy. Here we provide evidence indicating that antibody-producing cells in the intestinal mucosa of HIV-1-infected individuals have decreased capacity to switch from the production of IgM to IgA and IgG, the types of antibodies that normally restrict the translocation of bacterial antigens across the mucosal barrier. This may facilitate systemic dissemination of microbial products and subsequent inflammation in HIV-1-infected individuals. Furthermore, the accumulation of IgM in gut mucosa may contribute to the exacerbation of inflammatory processes by the formation of inflammatory immune complexes. This newly identified dysregulation of immune system alters our understanding of HIV-1 pathogenesis and may facilitate the design of novel therapies targeting immune dysfunction in HIV-1/AIDS.

Background Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioural risk factors, advanced HIV disease or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited. Methods We studied HIV-infected adult patients in care during 2006–2010 who had been prescribed ≥6 months of cART. We analysed the prevalence of selected key chronic conditions and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity. Results Of the 3,166 HIV-infected patients (median age 47 years, CD4+ T-cell count 496 cells/mm3, duration of cART use 6.8 years), 21% were female, 57% were non-Hispanic White and over half were current or former tobacco smokers. The five most frequent conditions among women (median age 45 years) were dyslipidaemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%) and low high-density lipoprotein cholesterol (HDLc; 27.3%). The five most frequent conditions in men (median age 47 years) were dyslipidaemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%) and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than White patients; Black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity. Conclusions Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among ageing HIV-infected patients.

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.

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.

Purpose HIV-related immunological and multisystem accelerated aging contributes to the premature occurrence of age-related comorbidities. Such non-AIDS-defining comorbidities include cardiovascular disease, dyslipidemia, osteoporosis and frailty, and are of increasing importance with improved survival on antiretrovirals. This review will describe the underlying pathogenesis of HIV-related accelerated aging and will thereafter focus on frailty, a clinical concept which has only recently been studied in the HIV field. Methods A literature search was performed using PubMed. Cited articles were peer reviewed and included prospective, retrospective and basic science studies, systematic reviews and Center for Disease Control and Prevention data. Results HIV infection is characterized profound immune dysregulation, which can hasten cardiovascular, renal, cerebrovascular and bone disease and precede their overt manifestation by years. Viral mediated atherogenesis further accelerates end organ dysfunction and increases mortality. Frailty, a clinical syndrome characterized by multisystem dysregulation and increased vulnerability to stressors, occurs prematurely in HIV-infected persons especially those with advanced disease. Frailty prevalence and clinical characteristics are similar in affected older adults and HIV-infected persons. Its presence is associated with a number of negative outcomes including greater comorbidity and hospitalization. Conclusion Premature frailty, like other non-AIDS-defining comorbidities, is a manifestation of HIV-related accelerated aging. The synergism of HIV infection and aging has alarming clinical and socioeconomic implications. Research is needed to identify the factors that predict the development of premature frailty among HIV-infected persons and the optimal prevention and management strategies.

(See the editorial commentary by Yin and Stein, on pages 406–408.)Background. We explored serum 25-hydroxyvitamin D (25[OH]D) levels and associated factors forinsufficiency or deficiency in an adult human immunodeficiency virus (HIV) cohort and compared 25(OH)Dlevels with those in the general US population.Methods. Usingbaseline datafrom theStudytoUnderstandtheNaturalHistory ofHIVandAIDSintheEraofEffective Therapy (SUN), a prospective, observational cohort study of HIV-infected adults enrolled at 7 HIVspecialtyclinicsin4UScitiesfromMarch2004toJune2006,weestimatedtheprevalenceofvitaminDinsufficiencyor deficiency (defined as 25(OH)D levels ,30 ng/mL), standardized by age, race, and sex. Using multiple logisticregression, we examined risk factors for vitamin D insufficiency or deficiency.Results. Among672SUNparticipantswithbaselineserum25(OH)DdeterminationswhowerenotreceivingvitaminD supplements, 70.3% (95% confidence interval [CI], 68.1%– 74.9%) were vitamin D insuffi cient or deficient, comparedwith79.1%(95%CI,76.7–81.3)ofUSadults.Factorsassociat edwithvitaminDinsufficiencyordeficiencyincludedblackrace(adjustedoddsratio[aOR],4.51;95%CI,2.59–7.85),Hispanicethnicity(aOR,2.78;95%CI,1.31–5.90),higherbodymassindex(aOR,1.04;95%CI,1.00–1.09),hypertension(aOR,1.88;95%CI,1.10–3.22),lackofexercise(aOR,3.14;95%CI,1.80–5.47),exposuretoefavirenz(aOR,1.98;95%CI,1.18–3.34),higherexposuretoultravioletlight(aOR,.78;95%CI,.71–.86),renalinsufficiency(aOR,.55;95%CI,.36–.83),andexposuretoritonavir(aOR,.56;95%CI,.35–0.89).Conclusions. SimilartofindingsinUSadultsgenerally,vitaminDinsufficiencyordeficiencyishighlyprevalentamongHIV-infectedadultsandisassociatedwithknownriskfactors.ObservedassociationsofvitaminDlevelswithrenal insufficiency and with use of ritonavir- and efavirenz-containing regimens are consistent with both HIV-relatedandtherapy-mediatedalterationsin vitaminDmetabolism. Cliniciansshouldconsiderscreening allpatientsfor vitamin D insufficiency or deficiency.Vitamin D is essential for calcium homeostasis and bonemetabolism [1]. Vitamin D deficiency is associated witha number of comorbidities, including hypertension,cardiovascular disease, insulin resistance, diabetes, dysli-pidemia, impaired immune function, decreased neuro-cognitive function, and malignancies [2–6]. The primarydeterminant of vitamin D status is exposure to sunlight.With increasing urbanizationand sunscreen use, vitaminD deficiency has become highly prevalent among thegeneral population [7, 8].Currently, serum concentration of 25-hydrox-yvitamin D (25[OH]D) is considered the best indicatorof vitamin D status, because it represents cumulative

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.

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 CD41 cell count, 462 cells/lL. 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.

Knowledge of an HIV-infected individual's sexual behaviors and routine sexually transmitted diseases (STDs) testing greatly facilitates HIV prevention efforts, but current data in older individuals are lacking. This study was developed to compare sexual behaviors and STD prevalence between older HIV-infected individuals and their younger counterparts. We conducted a cross-sectional cohort study of HIV-infected individualsor =18 years who completed an annual behavioral assessment. A total of 541 individuals completed the assessment. Analyses were performed to examine differences in sexual behaviors and STD prevalence between age groups: younger (18-35 years) (30%), middle-aged (36-49 years) (46%), and older (or =50 years) (24%). Older individuals were most likely to be male and Caucasian with longest time since HIV diagnosis, greatest receipt of highly active antiretroviral therapy (HAART), and highest rates of HIV RNA50 copies/mL (all p0.001). Reports of recent sexual activity decreased with age, younger (56%) vs. middle-aged (43%) vs. older (27%) (p0.001). The median number of recent sex partners was one (range 1-25) and 68% overall reported using condoms consistently; these parameters did not differ by age group. STD prevalence was 8% (gonorrhea [9], chlamydia [7], and syphilis [20]) and was highest among younger individuals (younger [11%] vs. middle-aged [7%] vs. older [3%]). Our results demonstrated that with older age, sexual activity declines but inconsistent condom use remains commonly reported. Furthermore, STDs were identified among all age groups. This latter finding reinforces the need for secondary prevention efforts among all individuals living with HIV/AIDS.

Antiretroviral therapy has revolutionized the care of individuals infected with the human immunodeficiency virus (HIV) and has fundamentally altered the scope of the disease. Acute renal failure and chronic kidney disease from medication toxicity and comorbid noninfectious illnesses are just as likely today as end-organ injury from the virus itself. Chronic immunosuppression renders HIV-infected patients vulnerable to any of several unique urological infections not frequently seen in immunocompetent patients. A deeper understanding of renal and urological emergencies in the context of the HIV-infected patient will better prepare the emergency physician to render optimal care to this rapidly expanding and aging patient population.

Background: The impact of premature frailty in HIV-infected individuals on the prevalence of sexual behaviors and sexually transmitted infections (STIs) is unknown. Methods: We compared these factors among individuals aged ≥18 years, who had prior determination of a frailty phenotype at the Washington University HIV Clinic between June and December 2008. All P values were 2-tailed and considered significant at

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.

Treatment of human immunodeficiency virus (HIV) infection with highly active combination antiretroviral therapy has increased survival and shifted the spectrum of HIV-associated morbidity and mortality from opportunistic infections toward a variety of other medical conditions. The prospective cohort Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) monitors the clinical course of HIV-infected individuals treated with combination antiretroviral therapy in 4 US cities. Every 6 months, clinical assessments, medical record abstraction, audio computer-assisted self-interview, and neurocognitive measurements are completed and blood and urine specimens are banked centrally. At enrollment and periodically thereafter, additional techniques such as anal cytology, dual energy x-ray absorptiometry, carotid ultrasonography, echocardiography, and abdominal and cardiac computed tomography are performed. From March 2004 through June 2006, 700 participants were enrolled; median age was 41 years, 76% were men, 58% were non-Hispanic white, 62% were men who have sex with men, 78% were taking combination antiretroviral therapy (of whom 86% had an HIV viral load of

Fat distribution changes, including peripheral fat loss and central fat gain, in HIV infection were first described as a “lipodystrophy syndrome.”1 Subsequent studies suggested that concurrent infection with the hepatitis C virus (HCV) may be associated with a higher prevalence of clinical lipodystrophy, particularly lipoatrophy, than in those with HIV infection alone.2–4 These findings are of concern because approximately one third of HIV-infected individuals in the United States are concurrently infected with HCV5 and fat changes in HIV infection have been associated with decreased quality of life and potentially compromised adherence to otherwise effective antiretroviral therapy.6 Effective antiretroviral therapy has been shown to slow down the progression of HCV-associated liver disease.7–9 Published studies that have investigated the association between concurrent HCV infection and lipodystrophy have been small and have defined lipodystrophy using subjective criteria of self-report confirmed by examination. The presence of facial or limb fat loss with or without central fat gain defined lipodystrophy in one study.3 Two other studies2,4 defined lipodystrophy as having lipoatrophy alone, lipohypertrophy alone, or a combination of lipoatrophy and lipohypertrophy. Furthermore, these studies included mainly men and may not be generalizable to women. Peripheral and central fat loss seems to predominate in HIV-infected men when measured using magnetic resonance imaging (MRI) and compared with control men.10 In HIV-infected women, peripheral fat loss also seems to predominate, but some women may have more upper trunk fat and visceral fat than control women.11 We present our findings on the association of HCV infection confirmed by HCV RNA testing with MRI-measured regional adipose tissue volume in a large cohort of HIV-infected men and women from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).

Liver disease is a leading cause of mortality for HIV-infected individuals in the antiretroviral therapy era, and hepatitis C virus (HCV) coinfection is a major factor [1, 2]. The prevalence of HCV coinfection is estimated to be 15%–40% among HIV-infected individuals [3–5]. However, higher rates of HCV coinfection have been reported in specific groups, including injection drug users [6]. Given the clinical significance of HCV coinfection, national guidelines recommend HCV antibody screening for all HIV-infected patients [7, 8]. However, false-negative results of serologic tests for HCV can occur in persons with acute HCV infection(during the period from exposure to HCV antibody seroconversion) and in those with chronic HCV infection. Chronic HCV viremia, or having detectable HCV RNA in serum (HCV RNA positivity) in the absence of detectable HCV antibodies (anti-HCV negativity), has been reported in HIV-uninfected [9–12] and HIV-infected individuals [13–17]. Experimental HCV infection of chimpanzees has also resulted in chronic HCV viremia without the development of HCV antibodies [18]. HIV-infected individuals may be at particular risk for seronegative HCV infection, possibly as a result of immunosuppression, with resultant failure to mount or maintain HCV antibody titers for detection by standard serodiagnostic tests [14, 17, 19]. The reported prevalence of chronic seronegative HCV infection among anti-HCV–negative, HIV-infected patients has varied between 0% and 13.2% [13, 15, 16, 20], depending upon the population studied and the HCV EIA used. Because the total reported number of HIV-infected patients with seronegative HCV infection is small, it has been difficult to establish the risk factors for seronegative HCV infection. We determined the prevalence of chronic seronegative HCV infection in a large, multicenter, nationally representative cohort of HIV-infected men and women. Using data combined from that cohort and data from 3 previously described cohorts, we analyzed the predictors of HCV RNA positivity among anti-HCV–negative, HIV-infected subjects to determine which groups of anti-HCV–negative subjects are at risk for having HCV RNA positivity.

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/m2). 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

Current antitretroviral therapy, although very effective in reducing the mortality and morbidity of HIV infection, remains challenged by the emergence of antiviral resistance. The development of a new class of antiretroviral drugs, based on the unique use of the chemokine receptor, CCR5, for initial viral entry into cells, offers an opportunity to overcome current resistance. Chemokine receptor antagonists, of which maraviroc is the leading product in development, are active in vitro and in vivo against both wild-type HIV and strains resistant to current drugs. Current Phase III trials help determine their place in HIV therapeutics, as well as the relative importance of viruses that utilize an alternative receptor, CXCR4.

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.

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.

(See the Major Article by Vanhommerig et al on pages 1678–85, and the Editorial Commentary by Reiberger on pages 1694–5.) Hepatitis C virus (HCV) coinfection is a leading cause of hospitalization and death among human immunodeficiency virus (HIV)-infected individuals in the United States and Europe [1–3]. Prevalent HCV infection is commonly associated with a history of current or past injection drug use (IDU) [4, 5]. Patients with a history of IDU who are not HCV infected remain at an increased risk of developing incident HCV infection [6, 7]. Furthermore, over the previous decade, cohort studies have demonstrated a rising HCV incidence among HIV-infected men who have sex with men (MSM) [7–20]. Most of these men with newly acquired HCV infection reported no history of IDU—their risk appears to be related to unprotected anal intercourse and noninjection drug use, especially amphetamines [21]. In 2010, the European AIDS Treatment Network published screening guidelines for incident HCV infection among HIV-infected individuals, recommending testing twice a year using serum alanine aminotransferase (ALT) and annually with HCV antibody (Ab) among MSM engaging in unprotected anal sex, as well as screening within 3 months of diagnosis of a new sexually transmitted infection (STI) or IDU exposure [22]. Mathematical modeling suggests that such a strategy would extend life expectancy and be cost-effective [23]. In the United States, STI guidelines published by the Centers for Disease Control and Prevention suggest considering annual HCV Ab screening for individuals at high risk of infection [24], but the definition of “high risk” is vague. Understanding current practices, as well as the rate of uptake of more routine screening for incident HCV infection, is essential to inform the development of evidence-based HCV screening strategies. We therefore used the Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) to investigate current and historical patterns of screening for HCV among HIV-infected individuals in the United States.

IntroductionHuman 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.MethodsParticipants 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.ResultsAmong 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).DiscussionPain 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.

OBJECTIVE Abnormalities in left ventricular morphology and function have been reported in HIV-negative infants exposed to antiretroviral therapy (ART) in utero that persists throughout preschool age. The objective of this study was to determine if these abnormalities persist, resolve, or worsen during preadolescence. DESIGN Cross-sectional observation study. METHODS Thirty HIV-negative children born to HIV-positive women and exposed to ART in utero (mean age 8 ± 2 years, 37% female, 74% African-American) and 30 HIV-negative children born to HIV-negative women (mean age 8 ± 3 years, 37% female, 76% African-American) underwent two-dimensional Doppler, tissue Doppler, and strain echocardiography to evaluate left ventricular systolic and diastolic function. RESULTS Weight, body surface area, heart rate and blood pressure were similar between groups. For the ART-exposed group, left ventricular mass index was lower (60 ± 9 vs. 67 ± 12 g/m, P < 0.02) and early diastolic annular velocity was lower (15.0 ± 2.2 vs. 16.3 ± 2.5 cm/s, P < 0.03) compared to controls. Left ventricular systolic function did not differ between groups. Lower maternal third trimester CD4 count was associated with lower early diastolic annular velocity; other non-HIV-related variables including cocaine use and increased maternal age correlated with lower left ventricular mass index. CONCLUSIONS Abnormalities in left ventricular systolic performance previously reported in HIV-negative infants and preschool aged children exposed to ART in utero were not apparent in preadolescent children. Left ventricular diastolic relaxation was reduced compared with controls suggesting residual effects of ART exposure on left ventricular diastolic function. Larger, longitudinal studies are necessary to confirm these observations.

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.

Serostatus disclosure is an important component of secondary HIV prevention with potential benefits for both the individual by experiencing increased social support and society by reducing HIV transmission risk behaviors. This cross-sectional study assessed disclosure patterns to sex partners, family members, and friends by sociodemographic and HIV-related factors among an urban, Midwestern U.S. HIV clinic population (n = 809); a majority of whom were African American and male with a mean age of 41 years. Almost three quarters (n = 596) of the sample was currently receiving HIV therapy, with 68% (n = 404) successfully suppressing their HIV viral loads. Among sexually activity individuals, 97% reported disclosing their serostatus to sex partners. This high rate of disclosure to sex partners suggests that social desirability may play a role in this self-reported measure. Approximately half of the sample (n = 359) disclosed to at least one family member and 60% (n = 474) disclosed to at least one friend. Disclosing to family members occurred more often among participants who were unemployed and endorsed depressive disorder symptoms (p < 0.05 for all). Disclosing to friends occurred more frequently among women, Caucasians and those who completed higher levels of education (p < 0.001 for all). HIV disclosure and disease severity were unassociated. Given the chronic nature of HIV care, additional research is needed to develop interventions to facilitate timely disclosure of HIV serostatus.

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.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.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-diagnosed5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02-2.91 vs. drinking3 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).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.

Low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected subjects. Initiation of antiretroviral therapy is associated with a 2%-6% decrease in BMD over the first 2 years, a decrease that is similar in magnitude to that sustained during the first 2 years of menopause. Recent studies have also described increased fracture rates in the HIV-infected population. The causes of low BMD in individuals with HIV infection appear to be multifactorial and likely represent a complex interaction between HIV infection, traditional osteoporosis risk factors, and antiretroviral-related factors. In this review, we make the point that HIV infection should be considered as a risk factor for bone disease. We recommend screening patients with fragility fractures, all HIV-infected post-menopausal women, and all HIV-infected men ⩾50 years of age. We also discuss the importance of considering secondary causes of osteoporosis. Finally, we discuss treatment of the more severe cases of bone disease, while outlining the caveats and gaps in our knowledge.

Understanding challenges to virologic suppression is essential to optimizing health outcomes among individuals with HIV. This cross-sectional behavioral assessment was conducted among 514 individuals presenting at an urban U.S. HIV clinic between June and September 2007. The majority of the sample was African American and male, with a mean age of 42 years. Most of the sample was receiving highly active antiretroviral therapy (HAART), and the majority of those had suppressed viral loads (HIV viral loads less than 400 copies per milliliter). By logistic regression analyses, African American/other minorities had 2.9 increased odds, those less than high school degree had 2.3 increased odds, those who were receiving ritonavir-boosted protease inhibitor therapy had 1.4 increased odds, and those who had expressed symptoms indicative of depressive disorders had 2.5 increased odds of having unsuppressed viremia as compared to Caucasians, those with more education, receiving non-nucleoside reverse transcriptase inhibitor-based therapy, and who had minimal depressive symptoms, respectively. These findings signify the importance of individualized interventions to enhance virologic suppression, both based on medication choices and individual characteristics.

HIV-related immunological and multisystem accelerated aging contributes to the premature occurrence of age-related comorbidities. Such non-AIDS-defining comorbidities include cardiovascular disease, dyslipidemia, osteoporosis and frailty, and are of increasing importance with improved survival on antiretrovirals. This review will describe the underlying pathogenesis of HIV-related accelerated aging and will thereafter focus on frailty, a clinical concept which has only recently been studied in the HIV field.A literature search was performed using PubMed. Cited articles were peer reviewed and included prospective, retrospective and basic science studies, systematic reviews and Center for Disease Control and Prevention data.HIV infection is characterized profound immune dysregulation, which can hasten cardiovascular, renal, cerebrovascular and bone disease and precede their overt manifestation by years. Viral mediated atherogenesis further accelerates end organ dysfunction and increases mortality. Frailty, a clinical syndrome characterized by multisystem dysregulation and increased vulnerability to stressors, occurs prematurely in HIV-infected persons especially those with advanced disease. Frailty prevalence and clinical characteristics are similar in affected older adults and HIV-infected persons. Its presence is associated with a number of negative outcomes including greater comorbidity and hospitalization.Premature frailty, like other non-AIDS-defining comorbidities, is a manifestation of HIV-related accelerated aging. The synergism of HIV infection and aging has alarming clinical and socioeconomic implications. Research is needed to identify the factors that predict the development of premature frailty among HIV-infected persons and the optimal prevention and management strategies.

With the aging of the Human immunodeficiency virus (HIV) epidemic, we are now faced with unprecedented and complex challenges, which need to be addressed in order to maximize care of the older HIV-infected population. Older persons have greater comorbidity than their younger counterparts. The compound effects of HIV infection, its treatment and increasing age on the incidence and prevalence of cardiovascular disease, malignancies, cognitive impairment, depression and frailty are of increasing concern.