Accelerated ageing of the immune system, caused by chronic
HIV infection, was strongly associated with harmful changes in the carotid
artery that may lead to long-term cardiovascular disease in women with HIV, US researchers report
in an article published in advance online by the Journal of Infectious Diseases.
People with HIV infection appear to have an elevated risk of
cardiovascular disease such as heart attack and stroke. People with HIV also
have a high frequency of subclinical signs of progressive cardiovascular
disease, or atherosclerosis, such as greater deposition of cholesterol and
other debris on the walls of arteries (plaques), and thickening of the walls of
the carotid artery.
In part these changes are due to lifestyle factors such as
smoking, which is more common in people with HIV, and raised cholesterol
levels caused by some antiretroviral drugs.
However there is growing concern that even in the absence of
multiple risk factors, long-term infection with HIV may directly increase the
risk of heart disease by promoting a permanent inflammatory state. Chronic
viral infections can also cause accelerated ageing of the immune system, which
may damage blood vessels in ways that promote the development of heart disease.
Dr Robert Kaplan of Einstein College of Medicine, New York,
led a study to investigate the effect of accelerated ageing of the immune
system on the cardiovascular health of women with HIV infection.
Ageing of the immune system (immunosenescence) is characterised
by a decline in the number of new naïve T cells manufactured, a loss of memory
T cells programmed to respond to specific infections, less aggressive
proliferation of T cells in response to infections and higher levels of some
inflammatory cytokines. All these defects explain why older people may be prone
to more infections, and to suffer more ill health when they do acquire an
These traits of an ageing immune system are usually seen in
the elderly, and have been linked to heart disease. This study set out to
determine if immunosenescence can also be found in younger people with HIV
infection, and the extent to which it predicted cardiovascular disease.
The study compared measures of carotid artery disease and
T-cell activation and immunosenescence in 115 HIV-infected women and 43 HIV negative
women matched by age and ethnicity. All were participants in the Women’s
Interagency HIV Study, a prospective study that included carotid artery
ultrasound scans in its investigations.
The investigators measured
T cell activation by looking at levels of co-expression of CD38 and
HLA-DR markers on CD+ and CD8+ T cells, and senescence by looking at the absence
of CD28 and presence of CD57 markers.
They found significantly higher frequencies of activated
CD4+ and CD8+ T cells, and of senescent CD8+ T cells, in HIV-positive women.
Activation was lower, but not absent, in women on fully suppressive
antiretroviral therapy, indicating that even very low levels of HIV continue to
cause immune dysregulation.
The level of activation in women with HIV was associated
with the extent of carotid artery lesions, after controlling for age, CD4
count, viral load and antiretroviral therapy. Activation in women without HIV
was lower and not associated with carotid artery lesions, suggesting either an
effect of HIV or concurrent pathogens such as CMV or hepatitis C on the
vascular wall, or the existence of a threshold of immune activation that is
necessary before it affects the vascular wall.
A higher level of CD8+ T cell senescence was significantly
associated with carotid artery lesions in HIV-positive women, but not in
HIV-negative women (p=0.009). This was not reversed by antiretroviral therapy.
The study is limited by its cross-sectional design which
relied on measurements and blood samples taken at one visit in women, and
prospective data are needed to further understand the links between immune
activation, immunosenescence and cardiovascular disease in people with HIV.
In an accompanying commentary Virginia Triant and Steven
Grinspoon of Massachusetts
say that long-term follow-up is needed to better understand the association
seen in this study, with further investigations required to see whether the same
phenomenon is found in men.
They also note that if the association holds in future
studies, attempts to treat immune senescence through immunosuppressive drugs,
cytokine inhibitors or teleomere-based therapies “will need to be balanced
against potential negative immunological effects. Indeed this balance may be
difficult to achieve.”