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CMV Antibody Levels Linked to Heart Disease Markers in Women On and Off ART
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2nd International Workshop on HIV and Aging, October 27-28, 2011, Baltimore, Maryland
Mark Mascolini
Cytomegalovirus (CMV) IgG antibody levels were associated with two carotid artery markers of cardiovascular disease in a Women's Interagency HIV Study (WIHS) comparison of 644 women with HIV and 100 without HIV [1]. Among women with an undetectable HIV load thanks to combination antiretroviral therapy (cART), WIHS researchers linked higher CMV IgG to an increased prevalence of carotid artery lesions.
Once a person becomes infected with CMV, this herpesvirus remains latent or persistent in that person for life. An earlier comparison of adults with and without HIV found that the proportion of CMV-specific CD8 cells was consistently higher in the HIV group [2]. CMV-specific cell levels measured in people with HIV were comparable to those observed in elderly people without HIV. A randomized, placebo-controlled study of 30 antiretroviral-treated people with a CD4 count persistently below 350 found that the anti-CMV drug valganciclovir significantly reduced CD8-cell activation [3]. Prior research also linked higher CMV IgG antibody levels to cardiovascular disease and all-cause mortality in elderly California Latinos not screened for HIV [4].
In the WIHS study, Robert Kaplan (Albert Einstein College of Medicine, Bronx) and colleagues hypothesized that circulating CMV IgG is associated with subclinical measures of vascular disease in HIV-positive women [1]. WIHS enrolls HIV-positive women and demographically similar women at risk for HIV in 6 US centers.
Kaplan and coworkers derived data for this analysis from a single WIHS visit women made in 2004 or 2005. The study group consisted of 601 HIV-positive women and 90 women without HIV, and the groups were well matched for age (median 41 to 42 years), race (predominantly black), and smoking status (half smoked). Most women in both groups were overweight or obese. The study excluded women negative for CMV IgG. The researchers divided HIV-positive women in three groups: treated/aviremic, treated/viremic, and untreated.
The investigators assessed the association between CMV IgG and five cardiovascular disease markers: carotid artery intima-media thickness, carotid artery distensibility, Young's elastic modulus, systolic and diastolic blood pressures, and pulse pressure.
Mean serum CMV IgG was significantly higher in women with than without HIV (25.4 +/- 9.9 versus 19.4 +/- 9.2 IU/mL, P < 0.01). CMV IgG level did not differ by race, smoking status, or diabetes status in HIV-negative women. But among women with HIV, mean CMV IgG was significantly higher in smokers (27.5 versus 23.7 IU/mL, P < 0.01) and diabetics (27.3 versus 24.9 IU/mL, P = 0.02) and marginally higher in blacks than in women of another race or ethnicity (25.9 versus 24.5 IU/mL, P = 0.11).
In HIV-positive women, older age correlated with higher CMV IgG (r = 0.24, P < 0.01), as did lower nadir CD4 count (r = -0.22, P < 0.01) and (marginally) current CD4 count (r = -0.08, P = 0.06). Older age also correlated with higher CMV IgG in HIV-negative women (r = 0.33, P < 0.01). Neither C-reactive protein (a marker of inflammation) nor body mass index correlated with CMV IgG in either group.
In an analysis adjusted for age, race, smoking status, diabetes, body mass index, C-reactive protein, and study site, lower carotid artery distensibility (indicating greater stiffness) correlated with each 10 IU/mL higher CMV IgG (r = -1.1, 95% confidence interval [CI] -1.7 to -0.4, P < 0.01). Vascular stiffness is a marker of early vascular disease.
Carotid artery intima-media thickness was not associated with CMV IgG in this analysis. But in an analysis of the three HIV-positive subgroups, the 226 treated and aviremic women with carotid lesions (carotid intima-media thickness greater than 1.5 mm, a precursor to atheroma) had significantly higher CMV IgG than women without carotid lesions (P< 0.05). That correlation was not found in the 148 treated/viremic women or the 227 untreated women.
In women with HIV, the researchers proposed, CMV may contribute to cardiovascular risk. They suggested that the impact of CMV on cardiovascular risk may differ by HIV disease stage. The association found between carotid lesions and CMV IgG in treated women with an undetectable HIV load could reflect their longer survival with HIV and/or immune dysregulation or reconstitution. In untreated women with a detectable HIV load, the impact of other vascular disease mechanisms may overshadow the impact of CMV.
"While emerging evidence suggests that control of CMV may improve control of HIV" [3], Kaplan and coworkers proposed, "our data suggest that treating CMV infection may also reduce cardiovascular risk in HIV-infected adults."
References
1. Parrinello CM, Sinclair E, Landay Al, et al. Cytomegalovirus IgG antibody is associated with subclinical carotid artery disease among HIV-infected women. 2nd International Workshop on HIV and Aging. October 27-28, 2011. Baltimore, Maryland. Abstract: O_16.
2. Naeger DM, Martin JN, Sinclair E, Hunt PW, Bangsberg DR, Hecht F, Hsue P, McCune JM, Deeks SG. Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS One. 2010;5(1):e8886. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008886.
3. Hunt PW, Martin JN, Sinclair E, Epling L, Teague J, Jacobson MA, Tracy RP, Corey L, Deeks SG. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis. 2011;203:1474-1483.
4. Roberts ET, Haan MN, Dowd JB, Aiello AE. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010;172:363-371. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950794/?tool=pubmed.
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