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1.  Pilot Study of Pioglitazone and Exercise Training Effects on Basal Myocardial Substrate Metabolism and Left Ventricular Function in HIV-Positive Individuals with Metabolic Complications 
HIV clinical trials  2013;14(6):303-312.
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.
doi:10.1310/hct1406-303
PMCID: PMC3934557  PMID: 24334183
exercise; HIV; insulin resistance; left ventricular dysfunction; metabolic syndrome
2.  The Alzheimer Disease-8 and Montreal Cognitive Assessment as Screening Tools for Neurocognitive Impairment in HIV-Infected Persons 
Journal of neurovirology  2013;19(1):109-116.
The diagnosis of HIV-associated neurocognitive impairment is time-intensive and often omitted in busy outpatient settings. Brief screening tools are needed. The Montreal Cognitive Assessment (MoCA) and the Alzheimer’s disease (AD)-8 have been used in neurodegenerative disorders. We evaluated the sensitivity and specificity of these brief screening tools in HIV-infected persons. The AD-8, MoCA, and formal neuropsychological testing were administered to 200 HIV-infected patients followed at a single institution. Normalized scores on formal neuropsychological testing were used to define neurocognitive impairment. The sensitivity and specificity of the MoCA and AD-8 were assessed to diagnose impairment. Neurocognitive impairment was highly prevalent in this cohort: 127 persons (64%) were diagnosed with neurocognitive impairment based on formal testing. Using the AD-8 and MoCA, 113 (57%) and 101 (51%) persons were identified with neurocognitive impairment, respectively. The sensitivity and specificity of MoCA were 63% and 71%, respectively. The sensitivity and specificity of AD-8 were 61% and 51%, respectively. Our findings highlight that brief screening tools correlate with formal neuropsychological testing. However, the sensitivities of these screening tools are lower than desired. Nevertheless, given their ease in administration, these tools could assist as a first line for identifying individuals who may subsequently require formal neuropsychological testing.
doi:10.1007/s13365-012-0147-5
PMCID: PMC3655767  PMID: 23345074
HIV; Neurocognitive Disorder; MoCA; AD-8; Neuropsychological Testing; Cognition
3.  Reduced Diastolic Function and Left Ventricular Mass in HIV-Negative Pre-Adolescent Children Exposed to Antiretroviral Therapy in Utero 
AIDS (London, England)  2012;26(16):2053-2058.
doi:10.1097/QAD.0b013e328358d4d7
PMCID: PMC3641749  PMID: 22874520
antiretroviral therapy; in utero; heart; children; diastolic
4.  Urban Farming: A Non-Traditional Intervention for HIV-Related Distress 
AIDS and behavior  2012;16(5):1238-1242.
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.
doi:10.1007/s10461-011-0061-5
PMCID: PMC3604898  PMID: 21986870
5.  Alcohol Consumption is Associated with Poor Health in HIV Clinic Patient Population: A Behavioral Surveillance Study 
AIDS and behavior  2011;15(1):209-213.
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.
doi:10.1007/s10461-009-9652-9
PMCID: PMC3621137  PMID: 20013042
HIV; Alcohol use; Screening; Viral load suppression
6.  Sexual Behaviors and Results of Bacterial Sexually Transmitted Infections Testing Among Frail HIV-Infected Individuals 
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 <.05.
Results
Of 445 individuals (71% male, 30% Caucasian, median age 43 years)assessed, the prevalence of frailty was 9%. Reports of recent sexual activity (44%) did not differ by frailty status. Consistent condom use (69% overall) was similar between sexually active frail and nonfrail individuals, and there was no significant difference in STI prevalence between groups (0 vs 32 [9%], P ¼ .08).
Conclusion
In this relatively young population, frailty did not affect reports of recent sexual activity or consistent condom use and no significant difference in STI prevalence was observed.
doi:10.1177/1545109709356946
PMCID: PMC3608415  PMID: 20071595
HIV; frailty; sexual behaviors; sexually transmitted infections
7.  Comparisons of sexual behaviors and STD prevalence among older and younger individuals with HIV infection 
AIDS care  2010;22(6):711-717.
This study was developed to evaluate differences in sexual behaviors and incident bacterial sexually transmitted diseases (STDs) between older HIV-infected individuals and their middle-aged and younger counterparts. We conducted a prospective cohort study of HIV-infected individuals ≥ 18 years who had completed an annual standard of care assessment. Analyses were performed to examine differences in sexual behaviors and incident STDs between age groups: (30%) were 18–35 years (younger), (46%) were 36–49 years (middle-aged) and (24%) were ≥ 50 years (older). 541 individuals completed the assessment. Older individuals were most likely to be male and Caucasian with longest time since HIV diagnosis, greatest receipt of HAART and highest rates of HIV RNA < 50 copies/mL (all p<0.001). Reports of recent sexual activity decreased with age, (56% younger vs. 43% middle-aged vs. 27% older) (p<0.001), the median number of sex partners was 1 (range 1–25) and 68% overall reported using condoms consistently. The number of sexual partners and consistency of condom use did not differ by age group. The STD incidence rate was 8% (gonorrhea [9], chlamydia [7] and syphilis [20]) and was higher among younger than older individuals (11% younger vs. 7% middle-aged vs. 3% older) (p=0.02). Our results demonstrated that reported sexual activity decreases with advancing age but did not improve consistency of condom use. Regardless of age, STDs continue to be identified and this finding reinforces the need for secondary prevention efforts among all individuals living with HIV/AIDS.
doi:10.1080/09540120903373573
PMCID: PMC3587156  PMID: 20467941
8.  Serostatus Disclosure Among Adults with HIV in the Era of HIV Therapy 
AIDS Patient Care and STDs  2012;26(1):29-35.
Abstract
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.
doi:10.1089/apc.2011.0183
PMCID: PMC3279708  PMID: 22107039
9.  Progression of Carotid Intima-Media Thickness in a Contemporary Human Immunodeficiency Virus Cohort 
Carotid artery intima-media thickness progression is associated with human immunodeficiency virus replication as well as with exposure to certain antiretroviral therapy regimens.
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.
doi:10.1093/cid/cir497
PMCID: PMC3174096  PMID: 21860012
10.  18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors 
Background
Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk.
Methods
We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m2, median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18FDG uptake into both carotid arteries and the aorta was compared between the two groups.
Results
Right and left carotid 18FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). 18FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18).
Conclusions
Carotid artery 18FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk.
doi:10.1186/1476-9255-9-26
PMCID: PMC3469335  PMID: 22726233
Pathophysiologic molecular-level biomarker; Atherogenesis; Non-invasive imaging; Infectious disease
11.  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
doi:10.1186/1475-2840-10-111
PMCID: PMC3258269  PMID: 22151886
insulin resistance; cardiac metabolism and function; PET-imaging
12.  Factors Associated with Seronegative Chronic Hepatitis C Virus Infection in HIV Infection 
Background
Chronic seronegative hepatitis C virus (HCV) infection is defined as being HCV antibody (anti-HCV) negative, but HCV RNA positivity occurs in individuals infected with human immunodeficiency virus (HIV). However, associated factors are not well established because of the small number of reported cases.
Methods
Multivariate logistic regression analysis of HIV-infected subjects from 4 cohorts (Tien et al., 2006; Bonacini et al., 2001; George et al., 2002; and Hall et al., 2004) determined factors associated with HCV RNA positivity in anti-HCV–negative subjects. HCV enzyme immunoassay 2.0 was used to determine anti-HCV status.
Results
Among 1174 anti-HCV–negative, HIV-infected subjects, the prevalence of seronegative HCV infection was 3.2% (95% confidence interval [CI], 2.2%–4.3%). History of injection drug use (IDU; OR, 5.8; 95% CI, 2.7–12.8), higher alanine aminotransferase (ALT) level (OR, 2.0 per doubling; 95% CI, 1.3–3.2), and CD4 cell count <200 cells/μL (OR, 2.3; 95% CI, 1.1–4.8) were associated with HCV RNA positivity in anti-HCV–negative subjects. Among those with a history of IDU who had either a CD4 cell count <200 cells/μL or an ALT level greater than the upper limit of normal, the prevalence of seronegative HCV infection was 24% (95% CI, 13%–39%).
Conclusions
Detectable HCV RNA in the context of a negative HCV enzyme immunoassay 2.0 result in HIV-infected patients is low, but higher than the reported prevalence in HIV-uninfected patients. Our findings suggest that HCV RNA testing should be performed in anti-HCV–negative, HIV-infected patients, especially those with a history of IDU and either a CD4 cell count <200 cells/μL or an abnormal ALT level.
doi:10.1086/511038
PMCID: PMC3170414  PMID: 17243063
13.  Association Between Hepatitis C Virus Coinfection and Regional Adipose Tissue Volume in HIV-Infected Men and Women 
Objective
Coinfection with hepatitis C virus (HCV) is reported to be associated with a higher prevalence of lipodystrophy than HIV infection alone. We examine the association between HCV and adipose tissue volume in HIV-infected men and women.
Methods
Cross-sectional analysis of HIV-infected subjects from the study of Fat Redistribution and Metabolic Change in HIV Infection. MRI measured regional adipose tissue volume. Detectable HCV RNA defined HCV infection.
Results
Twenty percent of 792 men and 26% of 329 women were HIV/HCV-coinfected. HIV/HCV-coinfected and HIV-monoinfected women had similar amounts of subcutaneous adipose tissue (SAT) in the leg, lower trunk, upper trunk, and arm and similar amounts of visceral adipose tissue (VAT). Similar findings were seen in men, except in the leg and VAT. After adjustment, HCV infection remained associated with more leg fat in men (12.2%, 95% confidence interval [CI]: 0.3 to 25.3; P = 0.043). Among those on stavudine, HIV-monoinfected men had less leg fat (−7% effect per year of stavudine use, 95% CI: −9 to −5; P < 0.001); a weaker association was seen in HIV/HCV-coinfected men (−2% effect, 95% CI: −7 to 3; P = 0.45). Indinavir was associated with less leg fat (−4% in HIV-monoinfected men, 95% CI: −6 to −1; P = 0.002; −5% in HIV/HCV-coinfected men, 95% CI: −11 to 2; P = 0.14).
Conclusions
Our findings suggest that HIV/HCV coinfection is not associated with less SAT in men and women. HCV infection seems to mitigate the loss of leg fat seen in HIV-infected men on stavudine.
doi:10.1097/QAI.0b013e3180423a95
PMCID: PMC3164885  PMID: 17356466
adipose tissue volume; fat distribution; hepatitis C virus; HIV; lipodystrophy
14.  Bone Disease in HIV Infection: A Practical Review and Recommendations for HIV Care Providers 
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.
doi:10.1086/656412
PMCID: PMC3105903  PMID: 20839968
15.  The Interplay of Sociodemographic Factors on Virologic Suppression Among a U.S. Outpatient HIV Clinic Population 
AIDS Patient Care and STDs  2010;24(4):229-235.
Abstract
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.
doi:10.1089/apc.2009.0275
PMCID: PMC2864061  PMID: 20397898
16.  Regional Adipose Tissue and Elevations in Serum Aminotransferases in HIV-Infected Individuals 
Background
The association of fat distribution with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations is not well-defined in HIV-infected individuals. Obesity is associated with hepatic steatosis, and ALT is a marker of steatosis in the general population.
Methods
Cross-sectional analysis of 1119 HIV-infected and 284 control subjects. Hepatitis C virus (HCV) RNA testing determined HCV infection. Magnetic resonance imaging measured regional adipose tissue volume.
Results
After adjustment for demographic and lifestyle factors, visceral adipose tissue (VAT) was positively associated with ALT in HIV/HCV-coinfected subjects (+9.8%, 95% confidence interval [CI]: 2.8 to 17.6), HIV-monoinfected subjects (+8.0%, 95% CI: 4.2 to 12.1), and controls (+5.9%, 95% CI: 2.0 to 10.1). In contrast, lower trunk subcutaneous adipose tissue (SAT) was negatively associated with ALT in HIV/HCV-coinfected subjects (−14.3%, 95% CI: −24.7 to −4.2) and HIV-monoinfected subjects (−11.9%, 95% CI: −18.4 to −5.3); there was a trend toward an association in controls (−7.1%, 95% CI: −22.7 to 5.9). Estimated associations between regional adipose tissue and AST were small and did not reach statistical significance.
Conclusions
More VAT and less lower trunk SAT are associated with elevated ALT, which likely reflects the presence of steatosis. There was little association with AST. HCV infection and having more VAT or less lower trunk SAT are independently associated with elevated ALT in HIV infection. Study regarding the association between VAT, trunk SAT, HCV, and progression of steatosis and fibrosis is needed in HIV-infected individuals.
doi:10.1097/QAI.0b013e3181685700
PMCID: PMC2776053  PMID: 18285711
adipose tissue; aminotransferase levels; hepatitis C virus; HIV; lipodystrophy

Results 1-16 (16)