Starting HIV treatment with a CD4 cell count below 350 associated with a key marker of cardiovascular risk

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 years.

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 = 0.007).

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 = 0.02).

“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 the authors.

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 inflammation.

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.”