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Heart Disease Signal Higher With 1 to 40 RNA Copies Than With 0 Copies
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
A viral load as low as 1 to 40 copies/mL was associated with increased carotid artery intima-media thickness (cIMT), a signal of cardiovascular disease, in a small comparison of patients with a 1- to 40-copy load and patients with completely undetectable viremia [1].
A growing body of research addresses associations between cIMT and HIV disease and treatment in adults [2,3] and adolescents [4]. But until this study by clinical investigators in Paris [1], no one had addressed the impact of detectable but sub-50-copy viremia on cIMT.
The investigators focused on 47 patients enrolled in a larger study of HIV, inflammation, and heart disease between March 2008 and June 2009. All enrollees were men who had taken antiretroviral therapy for at least 4 years and had a viral load below 40 copies. None of these men smoked. The researchers measured total cIMT and common carotid artery IMT (ccaIMT) in all 47 study participants at a single visit (the single-visit definition) and in a subset of 37 participants who had a viral load recorded 12 months before the study visit (the longitudinal definition).
In the total group, 14 people had detectable viremia between 1 and 40 copies and 33 had no detectable viremia. Age was similar in the two groups (43.7 in the detectable group and 40.6 in the undetectable group), as were an array of HIV and CD4 variables, including duration of HIV infection (13 versus 10.4 years, P = 0.5). Three people in the detectable group and none in the undetectable group were taking statins (P = 0.02).
Levels of proinflammatory markers, anti-inflammatory markers, and chemokines were largely similar between the people with 1 to 40 copies and the completely undetectable group.IL-10 was higher in the detectable group (0.94 versus 0.65 pg/mL, P = 0.03), as were IL-18 (213.8 versus 89.7 pg/mL, P = 0.06) and total adiponectin (3.61 versus 2.54 ug/mL, P = 0.07). But levels of 18 other markers did not differ between the two groups.
The researchers used three models to weigh the impact of low-level viremia on cIMT thickness: Model 1 adjusted for age, uncontrolled hypertension, and nadir CD4 count; model 2 adjusted for all those variables plus duration of antiretroviral therapy; and model 3 adjusted for all variables in model 1 plus time since most recent viral load above 50 copies.
With the single-visit definition, ccaIMT was significantly greater in people with 1 to 40 copies than in the completely undetectable group in all three statistical models (P < 0.05). With the longitudinal definition, both total cIMT and ccaIMT were significantly greater in people with low-level viremia in all three statistical models. (See poster link below for details of these analyses.)
The researchers called for larger longitudinal studies "to determine the clinical applicability of these findings, specifically using other measures of subclinical atherosclerosis and/or cardiovascular events."
References
1. Boyd A, Meynard JL, Morand-Joubert L, et al. IMT is associated with residual plasma viremia in treated patients with controlled HIV infection. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 803. http://www.retroconference.org/2012b/PDFs/803.pdf.
2. Mangili A, Polak JF, Skinner SC, Gerrior J, Sheehan H, Harrington A, Wanke CA. HIV infection and progression of carotid and coronary atherosclerosis: the CARE study. J Acquir Immune Defic Syndr. 2011;58:148-153.
3. Baker JV, Henry WK, Patel P, et al; Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy Investigators. Progression of carotid intima-media thickness in a contemporary human immunodeficiency virus cohort. Clin Infect Dis. 2011;53:826-835.
4. Vigano A, Bedogni G, Cerini C, et al. Both HIV-infection and long-term antiretroviral therapy are associated with increased common carotid intima-media thickness in HIV-infected adolescents and young adults. Curr HIV Res. 2010;8:411-417.
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