Starting HIV treatment with a CD4 cell
count below 350 cells/mm3 may increase the long-term risk of
cardiovascular disease, US research published in AIDS suggests. Investigators found that men who started therapy
with a CD4 cell count below this threshold had much poorer endothelial
function, a key measure of vascular health, than individuals who started
treatment when their CD4 cell count was above 350 cells/mm3.
The magnitude of the effect of starting HIV
therapy with a lower CD4 cell count was greater than that associated with
traditional risk factors for heart disease, including smoking or diabetes.
“A nadir CD4 T-cell count less than 350
cells/mm3 was associated with worse endothelial function in
HIV-infected men on stable HAART [highly active antiretroviral therapy],”
comment the authors. “Studies examining early HAART initiation with respect to
cardiovascular outcomes are needed.”
Cardiovascular disease is an increasingly
important cause of serious illness and death in patients with HIV. The exact causes
are controversial, but may include the side-effects of some antiretroviral
drugs and the inflammatory effects of HIV itself.
A low CD4 cell count may also have a role.
Investigators in San Francisco found that a lower nadir CD4 cell count was associated
with an increased risk of hardening of the arteries in HIV-positive men who
were taking long-term antiretroviral therapy.
Endothelial dysfunction (a condition when
the inner lining of blood vessels does not work properly) is another marker of
cardiovascular risk. The same team of investigators therefore designed a
cross-sectional study assessing the impact of lowest ever and current CD4 cell
count on endothelial function.
Their study population comprised 74
HIV-positive men. All were taking antiretroviral therapy and had an
undetectable viral load.
Endothelial function was assessed by
monitoring flow-mediated dilation in the right brachial artery.
Information on the patients’ cardiovascular
risk profile and nadir and current CD4 cell counts was obtained. A series of
analyses were then conducted to see if starting HIV therapy with a CD4 cell
count below 350 cells/mm3 (the then threshold for initiating
antiretroviral treatment) was associated with poorer endothelial function.
The patients had a median age of 47 years.
There was a high prevalence of traditional risk factors for cardiovascular
disease: 28% had high blood pressure, 32% elevated cholesterol and
triglycerides and 14% smoked. The median duration of HIV therapy was seven
The median nadir CD4 cell count was 314
cells/mm3 and the median current CD4 cell count was 659 cells/mm3.
Compared to individuals with a nadir CD4
cell count above 350 cells/mm3, those with a CD4 cell count below
this threshold were older (52 vs 44 years; p = 0.001), had been infected with
HIV for longer (14 vs 5 years; P < 0.0001), had a lower current CD4 cell
count (598 vs 810 cells/mm3; p < 0.0001), had a median nadir CD4
cell count of just 180 cells/mm3 vs 500 cells/mm3 (p
< 0.0001) and had been taking HIV therapy for longer (9 vs 4 years; p =
A nadir CD4 cell count was associated with
poorer endothelial function (p = 0.014).
This remained the case after controlling
for traditional risk factors for cardiovascular disease. Individuals with a
nadir CD4 cell count below 350 cells/mm3 had a 1.22% lower flow-mediated
dilation than individuals with a lowest ever CD4 cell count above this level (p
“This reduction in FMD [flow-mediated
dilation] represents a greater impairment than that associated with the
presence of diabetes, smoking, or prevalent cardiovascular disease,” comment
This association between nadir CD4 cell
count and poorer endothelial function remained significant in other analyses. These
took into account factors such as smoking intensity and other markers of
However, there was no evidence that current
CD4 cell count was associated with endothelial function.
“A low nadir CD4 T-cell count was the
strongest clinical predictor of endothelial dysfunction as assessed by brachial
artery FMD,” write the authors. “These findings suggest that delaying the
initiation of antiretroviral therapy until late in the disease process…may be
associated with adverse cardiovascular consequences.”