RESUMO
CONTEXT: Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population. OBJECTIVE: To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis. DESIGN: Cross-sectional study nested within the Multicenter AIDS Cohort Study. SETTING: Four US academic medical centers. PARTICIPANTS: There were 578 HIV-infected and 344 HIV-uninfected men. MAIN OUTCOME MEASURES: Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors. RESULTS: OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque. CONCLUSIONS: OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.
Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Infecções por HIV/complicações , Osteoprotegerina/sangue , Ligante RANK/sangue , Centros Médicos Acadêmicos , Adulto , Idoso , Cálcio/análise , Estudos de Coortes , Vasos Coronários/patologia , Estudos Transversais , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Estados UnidosRESUMO
OBJECTIVE(S): : To determine the effect of viral suppression on cross-sectional incidence testing. METHODS: : In 2001 and 2003, patients entering the Johns Hopkins Hospital (JHH) Emergency Department (ED) were enrolled into an interview-based identity-unlinked serosurvey. All HIV-positive samples were tested by the Vironostika-less sensitive (LS) enzyme immunoassay (EIA) (Organon-Teknika, Charteston, SC) and an avidity assay to determine recent HIV infection. Additionally 16 samples from 8 previously characterized elite suppressors (ES) were tested by cross-sectional incidence assays. RESULTS: : HIV prevalence was 12% for the 2001 survey and 11% for the 2003 survey. Of the HIV-infected subjects, 18% did not know they were infected. The Vironostika-LS EIA determined that 6% (11 of 183) and 7% (17 of 243) of HIV-positive individuals in 2001and 2003, respectively, were recently infected. Avidity testing confirmed that 6 of 11 in 2001 and 5 of 17 in 2003 were newly infected, leaving 17 discrepant samples. All 17 discrepant samples were Western blot-positive and viral load undetectable, and 7 of 17 had antiretroviral drugs (ARVs) in their serum. Ten individuals were virally suppressed without ARVs and seemed incident by the Vironostika-LS EIA but chronic by avidity testing. These 10 subjects had similar testing profiles to the known 16 ES samples, because 9 of 16 were incident by the Vironostika-LS EIA and 0 of 16 were incident by avidity testing. CONCLUSIONS: : By removing the viral load-negative individuals and confirming the initial Vironostika-LS EIA results by avidity testing, the incidence estimate was lowered from 1.73% to 0.94% per year in 2001 and from 1.90% to 0.56% per year in 2003. Viral suppression affects the performance of the cross-sectional incidence tests, which rely on antibody titer. In addition, 2% (10 of 426) of all HIV-infected individuals who use the JHH ED for medical care seem to suppress HIV to undetectable levels without ARVs.