No abstract

Older HIV-infected persons have a higher prevalence of hypertension, hypertriglyceridemia, low BMD, and lipodystrophy than matched controls, suggesting that HIV and treatment-related factors exceed "normal" aging in the development of those problems.

Background Identifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies. Methods Coronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multi-color flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV -related risk factors. Results Baseline characteristics for the analysis cohort (n=436) were: median age 42 years, median CD4 count 481cells/mm3, and 78% receiving ART. Higher frequencies of CD16+ monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors (OR per doubling was 1.66 for CD14+/CD16+ [p=0.02], 1.36 for CD14dim/CD16+ [p=0.06], and 1.69 for CD14var/CD16+ [p=0.01]). Associations for CD16+ monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers. Conclusions Circulating CD16+ monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.

Plasma inflammatory biomarkers that predict morbidity and mortality were strongly associated with monocyte activation and migration, modestly associated with T-cell maturation, and not associated with CD8(+) T-cell activation phenotypes. These findings suggest that strategies to control monocyte activation warrant further investigation.

HIV-associated neurocognitive disorders (HAND) persist despite great advancements in combination antiretroviral therapy (cART). The gold standard for diagnosing cognitive impairment consists of a time-consuming neuropsychological battery of tests given by a trained neuropsychologist, however in the outpatient HIV clinic this is not feasible. The International HIV Dementia Scale (IHDS) was developed to help identify individuals with cognitive impairment in the outpatient setting. The IHDS is moderately sensitive for detecting more symptomatic forms of HAND but sensitivity has been shown to be poor in mild impairment. The IHDS has not been evaluated in developed countries in large cohort populations. We conducted a prospective cross-sectional study of only HIV+ individuals in an urban clinic and evaluated the prevalence of HAND and associated risk factors for cognitive impairment using the IHDS. A total of 507 HIV+ individuals participated in the study of which the majority were male (65%) and African American (68%); and 41% had cognitive impairment. On multivariate analysis, African American race (p=2.21), older age (p=1.03), high school education or less (p=2.03) and depression (p=1.05) were associated with cognitive impairment. The high prevalence of HAND in this group suggests that more severe forms of HAND persist despite cART. Identified risk factors were non-HIV-related and suggest that environmental and sociodemographic factors have a significant impact on cognitive functioning and should be given more attention. The IHDS should be further evaluated in large cohort HIV+ and HIV− populations in the United States, as there remains a significant need to identify an effective brief screening tool for cognitive impairment.