BackgroundWe present a small longitudinal study of how demographic factors and persistent burdens of HIV and cytomegalovirus (CMV) influence cardiovascular health in young adults beginning ART in an inner-city clinic in Jakarta, Indonesia.MethodsART-naïve HIV patients [n = 67; aged 31 (19 to 48) years] were enrolled in the JakCCANDO Project. Echocardiography and carotid Doppler ultrasonography were performed before ART (V0) and after 3, 6, and 12 months (V3–12). Antibodies reactive with CMV lysate or IE-1 protein were assessed at each timepoint and CMV DNA was identified at V0.ResultsMarkers of adverse cardiovascular prognosis [left ventricular mass index, ejection fraction and carotid intimal media thickness (cIMT)] were similar to healthy controls, but increased at V12. Internal diameters of the carotid arteries and systolic blood pressure correlated with HIV disease severity at V0, but cardiac parameters and cIMT did not. E/A ratios (left ventricular diastolic function) were lower in patients with CMV DNA at V0, but this effect waned by V6. Levels of antibody reactive with CMV IE-1 correlated inversely with CD4 T cell counts at V0, and levels at V6–V12 correlated directly with the right cIMT.ConclusionsOverall the severity of HIV disease and the response to ART have only subtle effects on cardiovascular health in this young Asian population. CMV replication before ART may have a transient effect on cardiac health, whilst antibody reactive with CMV IE-1 may mark a high persistent CMV burden with cumulative effects on the carotid artery.

Periodontitis is a chronic inflammatory disease caused by the colonization of teeth by the bacterial plaque biofilm and the resultant host immune responses in adjacent periodontal tissues. Disease severity can vary dramatically between patients with periodontitis, with some subjects displaying inflammation without bony destruction (gingivitis), while others experience chronic progressive or rapidly aggressive gingival connective tissue damage and bone loss. To determine whether peripheral immune dysregulation is associated with periodontitis, we performed extensive analysis of immune cell subsets in peripheral blood from patients with chronic or aggressive periodontitis versus periodontally healthy control subjects. Peripheral blood mononuclear cells (PBMC) from patients with chronic periodontitis or aggressive periodontitis and from periodontally healthy controls were analysed by 8-10-colour flow cytometry for the frequencies of various lymphocyte subsets, including interleukin (IL)-17-, interferon (IFN)-γ-, tumour necrosis factor (TNF)-α- and IL-10-producing cells, and the frequencies and phenotype of monocytes. Cytokine levels in serum from the different groups were determined by Luminex assay. We found no significant differences in the frequencies of major immune cell populations [CD4 T cells, CD8 T cells, γδ T cells, CD4 CD45RO CD25 CD127 regulatory T cells (T ), CD19 B cells, CD14 monocytes] or of cytokine-producing T cells, or in the phenotype of CD14 monocytes in peripheral blood from these patient cohorts. Additionally, no significant differences were observed in serum levels of prototypical inflammatory cytokines. These results suggest that the local gingival inflammatory response is not reflected by obvious changes in major blood immune cell subset frequencies.

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 R2 = 0.36, P = 0.0013; Adjusted R2 = 0.40, P = 0.001, respectively). Conclusions: Our data identify periodontitis and CMV as independent predictors of atherosclerosis in young adult HIV patients.

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.