Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study.

Department of Infectious Diseases, Odense University Hospital, Denmark.
AIDS (London, England) (Impact Factor: 4.91). 06/2011; 25(13):1637-46. DOI: 10.1097/QAD.0b013e3283493fb0
Source: PubMed

ABSTRACT To assess the risk of cerebrovascular events (CVEs) in HIV-infected individuals and evaluate the impact of proven risk factors, injection drug abuse (IDU), immunodeficiency, HAART and family-related risk factors.
Nationwide, population-based cohort study.
The study population included all Danish HIV-infected individuals, a population-based comparison cohort and parents of both cohorts - all with no prior cerebral comorbidity. We computed incidence rate ratios (IRRs) of overall CVEs and CVEs with and without proven risk factors, stratifying the analyses on IDU. Impact of immunodeficiency, HAART, protease inhibitors, indinavir, didanosin, tenofovir and abacavir on risk of CVEs was analyzed using time-dependent Cox regression analyses.
HIV-infected individuals had an increased risk of CVEs compared with the comparison cohorts [(non-IDU HIV adjusted IRR 1.60; 95% confidence interval [CI] 1.32-1.94), (IDU HIV adjusted IRR 3.94; 95% CI 2.16-7.16)]. The risk was increased with and without proven risk factors. A CD4 cell count of 200 cells/μl or less before the start of HAART and exposure to abacavir increased the risk of CVE [(adjusted IRR 2.26; 95% CI 1.05-4.86) and (adjusted IRR 1.66; 95% CI 1.03-2.68)]. Protease inhibitors, indinavir, didanosin, tenofovir and HAART in general had no impact. Risk of CVEs was only increased in the parents of IDU HIV-infected individuals.
HIV-infected individuals have an increased risk of CVEs with and without proven risk factors. The risk is associated with IDU, low CD4 cell count and exposure to abacavir, but not with HAART. An association with family-related risk factors seems vague except for parents of IDU individuals.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Atherosclerosis is an inflammatory disease that is accelerated in human immunodeficiency virus (HIV) infection. Individuals with HIV infection have an activated type I interferon (IFN) monocyte phenotype, which may enhance uptake of modified low-density lipoprotein (LDL) thereby initiating a prefoam cell pathology and recruitment into atherosclerotic plaques. In a sampling of HIV-infected subjects, an increase in monocyte activation genes, MX1 and CXCL10, correlated with monocyte expression of the scavenger receptor A (SR-A), a major receptor for lipid uptake and foam cell formation. Monocytes from HIV-infected subjects accumulated more lipid than control uninfected subjects. We modeled increased activation in HIV infection by priming human monocytes with IFNα followed by exposure to acetylated LDL (acLDL). Exposure to IFNα increased acLDL uptake, which generated increased cellular reactive oxygen species (ROS). We posit that HIV infection augments formation of arterial plaques by triggering monocyte activation with a type I IFN profile, which induces SR-A expression, lipid uptake, and subsequent ROS production. These findings may explain in part why HIV-infected individuals with chronic immune activation have an increased risk of atherosclerosis.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 04/2014; · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract White matter (WM) abnormalities are frequently seen on brain MRI of HIV positive (HIV+) patients. We aimed to determine the prevalence of unexplained WM abnormalities and their associations with HIV disease and cardiovascular risk factors. We conducted a retrospective, cross-sectional study of brain MRI of HIV+ patients conducted between 2004 and 2009 at our center. Clinical and laboratory data were compiled, and images were independently reviewed for WM lesions. Images were obtained from 254 patients: 70% male, 53% white, 40% black, mean age 42 years, median current CD4 count 240 cells/mm(3), and 41% not taking antiretroviral therapy (ART). Hyperintense WM lesions were present in 161 patients (63.4%): 89 scans (35.0%) showed diffuse WM signal abnormality (DWMSA), 61 (24.0%) were consistent with small vessel disease (SVD, graded by Fazekas' scale), and 37 (14.6%) showed large asymmetrical focal WM lesions. SVD changes were associated with age and cardiovascular risk factors, and while cerebral SVD may be related to HIV infection, the MRI findings were not associated with HIV-related factors. The only risk factor for DWMSA was black race, and no correlation with cardiovascular risk factors, CD4 count, or clinical presentation was identified. DWMSA are therefore of uncertain neurological significance in HIV+ patients and could represent more than one clinicopathological entity.
    AIDS patient care and STDs 05/2014; · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most infectious pathogens have anecdotal evidence to support a link with stroke, but certain pathogens have more robust associations, in which causation is probable. Few dedicated prospective studies of stroke in the setting of infection have been done. The use of head imaging, a clinical standard of diagnostic care, to confirm stroke and stroke type is not universal. Data for stroke are scarce in locations where infections are probably most common, making it difficult to reach conclusions on how populations differ in terms of risk of infectious stroke. The treatment of infections and stroke, when concomitant, is based on almost no evidence and requires dedicated efforts to understand variations that might exist. We highlight the present knowledge and emphasise the need for stronger evidence to assist in the diagnosis, treatment, and secondary prevention of stroke in patients in whom an infectious cause for stroke is probable.
    The Lancet Infectious Diseases 05/2014; · 19.97 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014