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
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
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
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 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
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.”