Periodontitis and Cytomegalovirus Associate With Atherosclerosis Among HIV Patients After 5 Years on ART.

OBJECTIVES: Atherosclerosis has been linked with periodontitis in the general population and with persistent immune activation and a high burden of cytomegalovirus (CMV) in HIV patients responding to antiretroviral therapy (ART). Here, we assess risk factors for cardiovascular changes in younger HIV patients representative of patient populations in Asia. STUDY DESIGN: HIV-infected adults (n = 82) with <200 CD4 T-cells/µl were examined as they began ART at Cipto Mangunkusumo Hospital, Jakarta, and after 3 months. 32 patients were re-assessed after 5 years, alongside 32 age-matched healthy controls. METHODS: We assessed the community periodontal index of treatment needs, carotid -thickness (cIMT), plasma markers of immune activation (using commercial enzyme-linked immunosorbent assay) and CMV antibodies by in-house enzyme-linked immunosorbent assay. RESULTS: Periodontitis persisted in 16/32 patients after 5 years and was potentiated by greater age (P = 0.03) and poor oral hygiene (P = 0.05), with no effect of smoking, pulmonary tuberculosis, oral candidiasis, or low CD4 T-cell counts (P > 0.05). After 5 years on ART, right and left cIMT were greater in HIV patients with periodontitis (P = 0.02, 0.006, respectively). Moreover, cIMT values were higher in patients with periodontitis (P = 0.05-0.01) than in equivalent controls. Simple linear regressions showed that patients with periodontitis had greater right (P = 0.01) and left (P = 0.004) cIMT than those without periodontitis. Multiple linear regressions showed that periodontitis and CMV antibody levels optimally predicted poor right and left cIMT (Adjusted R = 0.36, P = 0.0013; Adjusted R = 0.40, P = 0.001, respectively). CONCLUSIONS: Our data identify periodontitis and CMV as independent predictors of atherosclerosis in young adult HIV patients.

Factors Affecting the Health of Retinal Vessels in Human Immunodeficiency Virus Patients Beginning Anti-Retroviral Therapy.

HIV patients responding to antiretroviral therapy (ART) have a high burden of cytomegalovirus (CMV) and display accelerated cardiovascular change assessed systemically. We assessed the effects of HIV, ART and CMV on retinal artery calibers (RAC), as a non-invasive measure of vasculopathy in HIV patients beginning ART. We analysed 79 HIV patients beginning ART in Jakarta, Indonesia, with a median (range) age of 31 (19-48) years. RAC was assessed using Image J software from fundus photos of both eyes, before ART (V0) and after 3-12 months (V3-V12). CMV DNA and antibodies were assessed. Systemic vascular pathology was assessed by carotid intima media thickness (cIMT). Multivariable models assessed which variables best predicted RAC values at V12. HIV patients had narrower retinal arteries and higher levels of CMV antibodies than healthy controls. RAC decreased over 12 months of ART (p < .0001). Right RAC correlated with CMV IE-1 antibody, while the left RAC at V3 correlated with cIMT. Multivariable models linked RAC at V12 with detectable HIV RNA at V12 and declared use of alcoholic drinks, while a smoking habit was protective. Decreases in RAC in HIV patients responding to ART suggest progressive microvascular change distinct from changes assessed in large vessels. Correlations with CMV IE-1 antibodies suggest the decline in RAC may be accelerated by frequent reactivations of CMV. This may be a feature of severe HIV disease before ART, confirmed by associations with high baseline HIV RNA in multivariable models. Links with alcohol consumption and smoking testify to a complex pattern of modifiable risk factors.

A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population.

OBJECTIVES: Meta-analyses have now confirmed that persistent infections with cytomegalovirus (CMV) can accelerate the onset of diseases of ageing, notably cardiovascular pathologies. We address the circumstances in which the association may be strong enough to warrant intervention to reduce the viral burden. RESULTS: We compare markers of the burden of CMV with established indices of vascular pathology in healthy adults (n = 82) and in renal transplant recipients (RTR; n = 81). Levels of all inflammatory and vascular biomarkers and CMV antibodies were higher in RTR, and flow-mediated dilation (FMD) values were lower indicating inferior endothelial function. In multivariable regression models without adjustment for estimated glomerular filtration rate (eGFR), CMV antibody levels, age and gender were independently associated with FMD in RTR, whilst only CRP associated with FMD in healthy adults. After adjustment for eGFR, associations between CMV antibody and FMD in RTR were reduced. METHODS: Carotid intima-media thickness, FMD, eGFR and plasma levels of CMV antibodies (reactive with a lysate, CMV IE-1 or CMV gB), ICAM-1, VCAM-1, P-selectin, sIFNαR2, sTNFR1, sCD14 and CRP were determined. CONCLUSION: Levels of CMV antibody predict declining endothelial health in RTR and not in healthy adults, presumably by reflecting a high burden of CMV. The levels of CMV antibodies were a poor reflection of plasma biomarkers thought to reflect 'inflammaging' or vascular damage.