Does CMV underlie the increased risk of cardiovascular disease in patients with HIV?

Michael Carter
Published: 16 April 2012

Cytomegalovirus (CMV) antibody levels are associated with some important markers of vascular disease in HIV-positive women, US researchers show in a study published in the online edition of the Journal of Infectious Diseases.

"Our findings suggest that CMV IgG [antibody level] is associated with increased carotid artery stiffness and carotid artery lesions in HIV-infected women," write the investigators. 

An association was also found between antibody levels and an increased risk of lesions in the carotid artery, but only for women taking HIV therapy and with an undetectable viral load.

The authors of an accompanying editorial believe the study takes us "one step closer to understanding the relationship between CMV and development of coronary heart disease."

Infection with CMV was linked to faster HIV disease progression and poorer outcomes in HIV-positive people in the era before highly active antiretroviral therapy (HAART) was available. Research conducted in the general, HIV-negative population has established a relationship between the infection and the development of cardiovascular disease.

It is well established that people with HIV have an increased risk of diseases such as heart attack and stroke. Investigators from the Women’s Interagency Health Study (WIHS) speculated that this could, in part, be because CMV infection causes subclinical vascular disease. They tested this hypothesis in a prospective study involving 601 HIV-positive women and 90 HIV-negative women.

All the study participants underwent a carotid artery ultrasound. The key measures of vascular disease assessed were arterial intima-media thickness (cIMT), distensibility (ability to be distended or stretched under pressure) and elasticity.

To see if CMV antibody level was associated with these key measures of arterial stiffness, the investigators performed a series of analyses which controlled for established risk factors of vascular disease.

Most of the women (64%) were African American and their mean age was 40 years. There was a high prevalence of risk factors for cardiovascular disease. Half the women were smokers, 20% were diabetic and the mean body mass index (BMI) was within the overweight/obese range.

Analysis of vascular health found little difference between the HIV-positive and HIV-negative women. Nor were there any significant differences between the HIV-positive women according to their use of antiretroviral therapy and viral load.

However, the investigators found that CMV antibody levels were significantly higher among the HIV-positive women compared to their HIV-negative peers (p < 0.01).

In the HIV-positive women, there was no significant relationship between CMV antibody levels and either CD4 cell count or viral load.

Nevertheless, the investigators identified a highly significant relationship between CMV antibody levels and carotid artery distensibility and elasticity (both p < 0.01) in HIV-positive women, but not in the HIV-negative control group.

“No associations between CMV IgG levels and subclinical cardiovascular disease parameters were observed in an HIV-uninfected control group that was studied using similar methods,” comment the researchers.

The magnitude of this association in the HIV-positive patients was similar to that associated with each additional two to three years of ageing.

Among the HIV-positive women, there was no overall association between CMV antibody levels and either cIMT or the presence of arterial lesions.

However, the presence of arterial lesions differed significantly according to the use of antiretroviral therapy and viral load.

For women taking virologically suppressive HIV therapy, each 10 iu/ml increase in CMV antibody titers was associated with a significant increase in the prevalence of lesions (prevalence ratio = 1.58; 95% CI, 1.09-2.30). This association was not observed in women with a detectable viral load.

“CMV-specific T-cell responses may expand among HIV-infected patients once they are placed on effective antiretroviral therapy, as compared with patients in the early or untreated phases of HIV infection or in HIV-uninfected controls,” suggest the authors. However, they believe that future research is needed to clarify this apparent association. This research should also “test the hypothesis that therapies directed against CMV infection may reduce HIV disease progression and associated vascular complications.”

The authors of the accompanying editorial hypothesise that the lesions observed in the women taking suppressive HIV therapy were due to immune reconstitution inflammatory syndrome (IRIS). They also believe that CMV may contribute towards the “aging” of the immune system, thereby increasing the risk of cardiovascular disease.

They conclude, “with a growing literature supporting the role of CMV in immune aging, inflammation and cardiovascular disease…further research on the immunology and epidemiology of CMV in HIV infected and non-infected populations is crucial.”

Reference

Parrinello CM et al. Cytomegalovirus IgG antibody is associated with subclinical carotid artery disease among HIV-infected women. J Infect Dis, online edition, 2012.

Aiello AE et al. CMV and immunological aging: the real driver of HIV and heart disease? J Infect Dis, online edition, 2012.