Total DNA was extracted from blood neutrophils with QIAmp DNA Blood Mini kits (Qiagen, Hilden, Germany)

Total DNA was extracted from blood neutrophils with QIAmp DNA Blood Mini kits (Qiagen, Hilden, Germany). 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 V6V12 correlated directly with the right cIMT. == Conclusions == Overall 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. Keywords:Anti-retroviral therapy, Cardiovascular disease, Cytomegalovirus, HIV == Introduction == Several studies have demonstrated accelerated age-related syndromes, such as vasculopathy, in HIV patients assessed in western settings. Most have addressed patients over 40 years of age, with consideration to traditional risk factors such as smoking, diet and exercise. In this context, the consensus view ascribes vascular pathology to systemic inflammation in untreated patients, where this declines on antiretroviral therapy (ART) and metabolic factors become dominant [13]. Cardiac parameters are less well studied, but Caucasian and African American patients receiving ART had a higher prevalence of diastolic dysfunction and higher left ventricular mass indices (LVMI) than healthy controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection [4,5]. However, ART changes patterns of cardiac dysfunction from myocarditis [caused by HIV itself or opportunistic infections including cytomegalovirus (CMV)] to syndromes mediated by autoimmunity and antiretroviral drug toxicities [6]. Hence cardiovascular risk in HIV patients on ART is more effectively predicted by the D:A:D algorithm based on Framingham scores and critical anti-retroviral drugs, than by Framingham scores alone [7]. Simulated interventions applied to an Asian population found smoking cessation had the greatest potential impact on 5-year predicted risks of cardiovascular disease, approximating the effect of (+)-Corynoline switching from abacavir to an alternate antiretroviral drug [8]. However abacavir is now used sparingly and the standard regimes cause minimal cardiovascular toxicity [9]. Several studies link a high burden of CMV with accelerated T-cell differentiation and cardiovascular disease in HIV patients stable on ART (e.g. [10]). One study showed that CMV prophylaxis can reduce immune activation [11], and may thus reduce vascular inflammation. Our study of Caucasian Australian patients stable after more than 2 years on ART correlated levels of antibody reactive with a lysate of CMV-infected fibroblasts with D:A:D scores [12]. However, studies of the younger HIV patients who predominate in Asian cohorts are rare, and the roles of persistent opportunistic infections (including CMV and tuberculosis; [6]) remain unclear. Here we address the effect of CMV and ART directly through standard measures of cardiovascular function applied to young adult Mouse monoclonal to Ractopamine patients beginning treatment with moderately advanced HIV disease in an inner city clinic in Jakarta, Indonesia. Patients from this clinic have high titres of antibody reactive with CMV [13] and many have tuberculosis. == Materials and methods == == Study population == The JakCCANDO Project is a comprehensive survey of clinical and immunological responses to ART undertaken in the outpatient clinic of Cipto Mangunkusumo Hospital (Jakarta, Indonesia). We enrolled 82 ART-nave HIV patients in 20132014 with <200 CD4 T-cells/l. The study was approved by Universitas Indonesia, Cipto Mangunkusumo Hospital and Curtin (+)-Corynoline University ethics committees. Written consent was obtained from each subject. Examinations were performed before ART initiation (V0) and at months 3, 6 and 12 (V3, V6, V12). Subjects were also tested for pulmonary tuberculosis (chest X-ray and sputum acid bacilli smear) at V0. Plasma HIV RNA loads were determined using AmpliPrep/COBASTaqManHIV-1 Tests (version 2.0) and CD4 T-cell counts were determined using standard flow cytometric techniques. == Cardiovascular assessments == Echocardiography and vascular Doppler examinations used an ESAOTE ultrasonography unit (Genova, Italy), with a LA522E ultrasound probe to evaluate the carotid artery and a PA230E probe to evaluate the heart. For cardiac examinations, the probe was (+)-Corynoline positioned on the chest wall to gain B-mode and M-mode views. Parameters recorded included the Ejection Fraction (EF; the percentage of blood leaving the heart at each contraction) and the E/A ratio [ratio of the early (E) to late (A) ventricular filling velocities marking the ability of the left ventricle.