Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND).

HIV-associated neurocognitive disorders (HAND) continues to be prevalent (30-50%) despite plasma HIV-RNA suppression with combination antiretroviral therapy (cART). There is no proven therapy for individuals on suppressive cART with HAND. We have shown that the degree of HIV reservoir burden (HIV DNA) in monocytes appear to be linked to cognitive outcomes. HIV infection of monocytes may therefore be critical in the pathogenesis of HAND. A single arm, open-labeled trial was conducted to examine the effect of maraviroc (MVC) intensification on monocyte inflammation and neuropsychological (NP) performance in 15 HIV subjects on stable 6-month cART with undetectable plasma HIV RNA (<48 copies/ml) and detectable monocyte HIV DNA (>10 copies/10(6) cells). MVC was added to their existing cART regimen for 24 weeks. Post-intensification change in monocytes was assessed using multiparametric flow cytometry, monocyte HIV DNA content by PCR, soluble CD163 (sCD163) by an ELISA, and NP performance over 24 weeks. In 12 evaluable subjects, MVC intensification resulted in a decreased proportion of circulating intermediate (median; 3.06% (1.93, 6.45) to 1.05% (0.77, 2.26)) and nonclassical (5.2% (3.8, 7.9) to 3.2% (1.8, 4.8)) CD16-expressing monocytes, a reduction in monocyte HIV DNA content to zero log10 copies/10(6) cells and in levels of sCD163 of 43% by 24 weeks. This was associated with significant improvement in NP performance among six subjects who entered the study with evidence of mild to moderate cognitive impairment. The results of this study suggest that antiretroviral therapy with potency against monocytes may have efficacy against HAND.

Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder.

We assessed ferumoxytol-enhanced brain MRI to identify monocyte/macrophage accumulation in HIV-associated neurocognitive disorder (HAND). Four HIV-infected subjects with undetectable HIV RNA levels on antiretroviral therapy, HIV DNA level in CD14+ cells ≥10 copies/10(6) cells, and cognitive impairment underwent ferumoxytol-enhanced brain MRI. On post-ferumoxytol susceptibility-weighted images, all HIV-infected subjects demonstrated a diffuse "tram track" appearance in the perivascular regions of cortical and deep white matter vessels suggesting ferumoxytol uptake in monocytes/macrophages. This finding was not present in an HIV-seronegative control. While ferumoxytol may have potential as an imaging biomarker for monocyte/macrophage accumulation in patients with HAND, future study is needed.

Oxidative mitochondrial DNA damage in peripheral blood mononuclear cells is associated with reduced volumes of hippocampus and subcortical gray matter in chronically HIV-infected patients.

Cross-sectional relationships were examined between regional brain volumes and mitochondrial DNA (mtDNA) 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral blood mononuclear cells (PBMCs) of 47 HIV patients [mean age 51years; 81% with HIV RNA ≤50copies/mL] on combination antiretroviral therapy. The gene-specific DNA damage and repair assay measured mtDNA 8-oxo-dG break frequency. Magnetic resonance imaging was performed at 3T. Higher mtDNA 8-oxo-dG was associated with lateral ventricular enlargement and with decreased volumes of hippocampus, pallidum, and total subcortical gray matter, suggesting the involvement of systemic mitochondrial-specific oxidative stress in chronic HIV-related structural brain changes and cognitive difficulties. Clarification of the mechanism may provide potential therapeutic targets.

Frailty Characteristics in Chronic HIV Patients are Markers of White Matter Atrophy Independently of Age and Depressive Symptoms: A Pilot Study.

BACKGROUND: Chronic HIV disease is associated with neurocognitive impairment and age-related conditions such as frailty. OBJECTIVE: To determine whether regional brain volumetric changes correlate with frailty parameters in older (≥ 40 years) HIV+ patients on stable combination antiretroviral therapy. METHOD: Thirty-five HIV-infected participants in the Hawaii Aging with HIV Cohort - Cardiovascular Disease study underwent T1-weighted brain magnetic resonance imaging, frailty assessment and neuropsychological testing. Five physical frailty traits were assessed: low physical activity; exhaustion; unintentional weight loss; weak hand grip strength; slow walking speed. Linear regression quantified cross-sectional relationships of 12 brain regions to walking times and hand grip strength. RESULTS: Participants were 50.6 ± 6.8 years old and 77% had undetectable plasma viral load. One subject was frail (possessing ≥ 3 frailty traits); 23% were pre-frail (1-2 frailty traits) and had worse composite learning and memory z-scores than did non-frail individuals (p=0.06). Pre-frail or frail subjects had reduced hand grip strength relative to the non-frail group (p=0.001). Longer walking times (slower gait) related independently to lower volumes of cerebellar white matter (p<0.001, ß=-0.6) and subcortical gray matter (p<0.05, ß=-0.30). Reduced thalamus volume was linked to weaker grip strength (p < 0.05, ß=0.4). Caudate volume was negatively associated with grip strength (p<0.01, ß=-0.5). CONCLUSION: Volumetric changes in cerebellar white matter and subcortical gray matter, brain regions involved in motor control and cognition, may be connected to frailty development in well-controlled HIV. Gait speed is particularly sensitive to white matter alterations and should be investigated as a predictor of frailty and brain atrophy in chronically infected patients.

Neurocognitive deficits associated with the hepatitis C virus among incarcerated men.

The purpose of this preliminary study was to examine cognitive functioning in inmates with the hepatitis C virus (HCV) and to investigate relationships among performance on the Repeatable Battery for the Assessment of Neuropsychological Status-Form A (RBANS; Randolph, 1998). Data from 43 HCV+ inmates were reviewed retrospectively and compared with a sample of HCV- inmates. Significant differences were found on two of five indices (Attention: U = 537.5, p = .003; r = -.32; Total: U = 643.0, p = .048; r = -.22) and four subtests: Coding (U = 326.0, p <.001, r = -.53), Digit Span (U = 634.0, p = .038, r = -.22), Story Memory (U = 625.5, p = .032, r = -.24), and Story Recall (U = 548.5, p = .004, r = -.31), with the HCV group scoring lower on all significant measures. In this study the RBANS proved to be an efficient measure with clinical utility among an HCV population. Within this incarcerated population patterns of performance were "typical" of current literature, with impaired attention appearing earlier in the disease process, and the study invites further exploration into proposed cognitive deficits among this population where HCV is highly prevalent.

Predictors of 25-hydroxyvitamin D levels in HIV-infected patients in Hawai'i.

HIV-infected individuals are at increased risk for several metabolic diseases, including low 25-hydroxyvitamin D [25(OH)D]. Data on the prevalence and risk factors for low 25(OH)D in HIV patients living in the tropics is scarce. Patients ≥ 40 years old on stable antiretroviral therapy were enrolled from March 2009 to July 2011 in Hawai'i (latitude 21° North). Chemiluminescent immunoassay (DiaSorin) was used to determine plasma 25(OH)D levels. Patients were grouped by whether 25(OH)D was collected in summer (May 1 - September 30) or winter (October 1 - April 30). Of 158 patients enrolled, 88 (56%) and 70 (44%) were enrolled in winter and summer, respectively. There were 57.6% Caucasians and 88% men. Over-all median (quartile1, quartile3) age was 51 (46, 57) years and median 25(OH)D was 32.4 (24.0, 41.0) ng/ml. Forty-three percent (n=68) had 25(OH)D<30.0 ng/ml. Median 25(OH)D levels were 29.6 (22.0, 38.0) ng/ml in winter and 36.9 (25.0, 44.5) ng/ml in summer (P = .01). Median body mass index (BMI) of winter patients was significantly higher (P = .03). By simple linear regression, log-transformed 25(OH)D was significantly associated with winter visit (ß = -.0737, P = .01), ethnicity (Caucasian versus non-Caucasian, ß = .1194, P < .01), BMI (ß = -.0111, P < .01) and current use of zidovudine (ß = -.1233, P = .03). In multiple linear regression, only Caucasian ethnicity (ß = .1004, P < .01) and BMI (ß = -.0078, P = .02) retained statistical significance. Seasonal variation in 25(OH)D was observed but the significance of winter visit was not preserved in the final multivariate model. Ethnicity and BMI were better predictors of 25(OH)D levels than season in the tropics.

Poorer neuropsychological performance increases risk for social services among HIV-infected individuals.

HIV-Associated Neurocognitive Disorder (HAND) is a prevalent condition among persons with HIV resulting in cognitive impairments that may impact daily functioning. The relationship between neuropsychological (NP) test performance and functional status was investigated based on social services received (SSR) among 285 HIV-infected and 242 HIV-negative participants enrolled in the Hawai'i Aging with HIV Cohort. HIV-infected participants scored significantly lower than the HIV-negative group on all measures of NP testing and also reported receiving SSR at a higher rate. Among HIV-infected participants, more SSR correlated with poorer overall global NP performance (ρ = -0.25, P < .001), as well as poorer performance in NP domains assessing psychomotor speed (ρ = -0.25, P < .001), and learning and memory (ρ = -0.19, P = .02). NP test performance did not correlate with the number of SSR among HIV-negative participants. Supplemental Security Income (SSI) was the most commonly utilized social service among HIV-infected. Receiving SSI was associated on multivariate analysis with poorer NP performance independent of lack of full time work, or nadir CD4 count. Poorer NP performance among HIV-infected individuals is associated with increased risk for social services. Interventions to address causes of cognitive dysfunction in this population may decrease demand for social services.

Albuminuria as a marker of cardiovascular risk in HIV-infected individuals receiving stable antiretroviral therapy.

UNLABELLED: Albuminuria (urinary excretion of more than 30 milligram of albumin per gram of creatinine) serves as an indicator of microvascular injury, which has been associated with atherosclerosis and cardiovascular disease in HIV-seronegative individuals. Albuminuria has been reported to be prevalent among HIV-seropositive individuals, however, the relationship between albuminuria and risk for cardiovascular disease in this population has not been well-studied. We examined the relationships between albuminuria and parameters of atherosclerosis including carotid intima-media thickness and traditional cardiovascular risk assessment among HIV-seropositive individuals receiving stable antiretroviral therapy. We utilized a cross-sectional baseline data from the Hawai'i Aging with HIV-Cardiovascular Study cohort. RESULTS: Data was available on 111 HIV-infected patients (median age of 52 (Q1,Q3: 46, 57), male 86%; diabetes 6%; hypertension 33%; dyslipidemia 50%; median CD4 count of 489 cells/mm(3) (341, 638); HIV RNA PCR < 48 copies/ml of 85%). Eighteen subjects (16.2%) had microalbuminuria, and two subjects (1.8%) had macroalbuminuria. Albuminuria was significantly associated with increased Framingham Risk Score (P=.002), insulin resistance by HOMA-IR (P=.02), diastolic blood pressure (P=.01), and carotid intima-media thickness (P =.04). The correlation between the amount of albuminuria and carotid intima-media thickness remained significant even after adjusting for age, gender, ethnicity, current smoking status, diabetes mellitus, diastolic blood pressure, fasting insulin level, CD4 count, and HIV-RNA viral load. CONCLUSION: Albuminuria is prevalent among HIV-infected patients receiving stable antiretroviral therapy. It is significantly related to previously defined markers of cardiovascular disease and metabolic syndrome among HIV-infected patients receiving stable antiretroviral therapy.

The psychology of patient compliance: a focused review of the literature.

BACKGROUND: Excellent patient compliance to periodontal maintenance is absolutely necessary for successful long-term therapy. However, absolute (100%) compliance is rare, having been reported as low as 16%. Although social, behavioral, cultural, and economic factors have been implicated as determinants in patterns of compliance, the influence of personality characteristics on attitudes remains to be carefully explored. This focused review of the literature explores current research addressing psychologic factors associated with compliance to periodontal maintenance therapy. METHODS: A literature search of PubMed electronic database was conducted, inclusive of the years 1990 to 2011. The search used MeSH terminology such as periodontal maintenance, emotional intelligence, personality, patient compliance, etc. In addition, searches were conducted of reference lists from original research and review articles. Studies were assessed with respect to methodology and design, statistical analysis, and psychologic measurements. RESULTS: Non-compliant patients appear to have a higher frequency of stressful life events. Studies suggest that initial patient response to periodontal therapy may be related to emotional intelligence. Regarding personality factors, high neuroticism and low conscientiousness are most widely associated with non-compliance. As such, increased knowledge of the "Big Five" personality factors (i.e., neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) could assist clinicians in potentially increasing compliance among patients. Clinicians could also incorporate a working knowledge of the Health Belief Model and Theory of Planned Behavior to develop individualized treatment strategies for patient compliance. CONCLUSION: Non-compliance to periodontal maintenance cannot be solely explained by one determinant but rather may involve an individual's health beliefs, emotional intelligence, psychologic stressors, and personality traits.