Factors affecting affect cardiovascular health in Indonesian HIV patients beginning ART

Abstract

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.

Active and Persistent Cytomegalovirus Infections Affect T Cells in Young Adult HIV Patients Commencing Antiretroviral Therapy

“…Levels of CMV lysate antibody at any visit correlated with age, whilst high levels of CMV IE-1 antibody associated with low CD4 T-cell counts at V0. This supports CMV lysate antibody as a marker of the lifelong burden of CMV, whilst CMV IE-1 antibody may mark recurrent CMV reactivations in patients with a history of severe immunodeficiency (6,19).…”

“…Associations between these measures of CMV burden and cardiovascular change in our cohort have been described (19). Table 1: The presence of CMV DNA before ART associated with higher CMV antibody levels on ART.…”

“…The JakCCANDO study cohort (Jakarta CMV Cardiovascular ART Neurology Dentistry Ophthalmology) at the HIV/AIDS clinic of Cipto Mangunkusumo Hospital (Jakarta, Indonesia) comprised 82 ART-naive HIV patients aged 18 -40 years, beginning ART with <200 CD4 T-cells/µl in 2013-14 (19). Blood samples were collected before ART (V0) and 1, 3, 6, and 12 months later (V1-V12).…”

“…Primer and probe sequences targeting the UL54 gene have been described previously (19). Total DNA was extracted with QIAmp DNA Blood Mini kits (Qiagen; Hilden, Germany) and stored at -80°C.…”

“…We also assessed the activation and differentiation of CD4 and CD8 T-cells before and on ART, with plasma C-reactive protein (CRP) as a marker of immune activation, and levels of a soluble receptor of type 1 interferons (sIFNR). This can regulate the activity of IFN through competition at high concentrations and stabilization at lower concentrations (19). Whilst HIV and CMV induce sIFNin vitro, the short half-lives of these molecules hamper meaningful analyses in vivo.…”