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Left ventricular dysfunction in HIV infected anti-retroviral therapy naive patients
1National Institutes of Health, National Institute of Allergy and Infectious Diseases - Bethesda - United States of America
2Leidos Biomedical Research, AIDS Monitoring Laboratory - Frederick, MD - United States of America
Background Cardiovascular disease is one of the leading causes of mortality in individuals with chronic human immunodeficiency virus (HIV) infection. In particular, antiretroviral therapy (ART) naïve patients with low CD4+ counts have higher incidence of co-infections, systemic inflammation and coagulopathy which can be associated with both ischemic and non-ischemic cardiomyopathy. The prevalence of heart failure/left ventricular dysfunction in ART naïve individuals with severe CD4 lymphopenia is unknown.
Objective Identify the prevalence of left ventricular dysfunction/heart failure in patients with less than 100 CD4+ T cells/µL at the time of ART initiation and identification of immunological correlates that can guide management.
Methods 206 HIV+ ART naïve patients with CD4<100 cells/µL were included in a prospective study and followed longitudinally for 192 weeks after ART initiation. Demographic, virologic and clinical data were analyzed. Plasma cytokines were measured with ELISA and electrochemiluminescence assays. Echocardiograms were performed as clinically indicated. Statistical analyses were performed using Mann-Whitney non-parametric tests.
Results The median age at enrollment was 38 years old (yo),(range: 21-75), 75.7% of the patients were male and 57.7% were African American. The median HIV viral load (VL) was 138,005 copies/ml and the median CD4 was 24 cells/µl. Out of the 206 patients, 80 had an echocardiogram, 67 of which were performed in the first 100 days of ART (64% male, median age 41yo). 13 out of these 67 patients (19%) had reduced ejection fraction (EF <50%) and 6 out of these 13 had EF<40%. Four patients had right ventricular systolic pressure > 40 mm Hg. The median CD4 count and HIV viral load of the patients with echocardiographic abnormalities on the day of the study did not differ from those without echocardiographic abnormalities (14 cells/µl vs 32 cells/ µl, p=0.0793, and 108,444 copies/ml vs 28,279 copies/ml, p=0.3059). Patients with ventricular dysfunction had significantly higher plasma levels of D-Dimer (1719 vs 949.8 ng/ml), (p=0.0271) and IL-6 (4.288 vs 1.656 pg/ml), (p<0.0001) prior to ART. No significant differences were found in plasma levels of TNF, CRP and sCD14.From the 17 patients with evidence of ventricular dysfunction, 11 had a follow up echocardiogram, out of which 5 had ventricular function improvement (EF>50) after therapy (median follow up 9 months, range 4-24 months). Two patients died during the first 100 days of ART initiation, of whom one had heart failure with EF<40% and one did not.
Conclusions Left ventricular dysfunction is an important comorbidity in ART naïve patients with severe lymphopenia and is associated with higher levels of IL-6 and D-dimer. These data suggest that specific cardiac screening for ART-naïve HIV patients with severe lymphopenia should be further evaluated.
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