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Starting ART below 350 CD4 Cells is Associated with Impaired Artery Function

HIV positive people who ever had a CD4 T-cell count below 350 cells/mm³ are more likely to have reduced flow-mediated dilation, a sign of blood vessel dysfunction linked to cardiovascular events such as heart attacks, according to a study described in the June 1, 2012, issue of AIDS. These findings suggest that starting antiretroviral treatment above this CD4 level may be beneficial.

Several observational studies have found that HIV positive people have higher rates of cardiovascular disease and related events, but it is not yet clear whether this is due to HIV infection itself, resulting immune activation and inflammation, side effects of antiretroviral drugs, traditional risk factors, or some combination thereof. It is not yet clear how timing of HIV treatment might influence cardiovascular risk.

Jennifer Ho from Massachusetts General Hospital in Boston and colleagues looked at the association between endothelial function and CD4 cell counts in HIV positive men on combination antiretroviral therapy (ART) with undetectable plasma HIV viral load.

This cross-sectional (single time-point) study included 74 men with a median age of 47 years. The median current CD4 count was high, at 659 cells/mm³, with a median nadir or lowest-ever count of 314 cells/mm³. One-third had hyperlipidemia (abnormal blood lipid levels), 28% had hypertension (high blood pressure), and 14% were smokers.

Participants underwent non-invasive assessment of endothelial function using brachial artery flow-mediated dilation (FMD), which measures how well arteries in the upper arms respond to changes in blood flow. Healthy blood vessels are elastic and can expand when called on to carry more blood. As atherosclerosis develops, cholesterol, calcium and other material builds up in the artery walls, making them stiff and non-responsive. Eventually arteries can become blocked, leading to heart attack or stroke.

Results

• People with CD4 nadirs below 350 cells/mm³ and those with higher levels had some significant differences:

o      Older age (52 vs 44 years, respectively);

o      Longer duration of HIV infection (14 vs 5 years);

o      Lower median current CD4 count (598 vs 810 cells/mm³);

o      Lower median nadir CD4 count (180 vs 500 cells/mm³.

• Having a nadir CD4 count below 350 cells/mm³ was significantly associated with reduced flow-mediated dilation after adjusting for age and race/ethnicity.
• Nadir CD4 count remained an independent predictor of reduced FMD after adjusting for cardiovascular risk factors including smoking, hyperlipidemia, hypertension, and diabetes.
• CD4 nadir continued to predict reduced FMD after adjusting for HIV-related characteristics including duration of infection and ART use.
• In a multivariate analysis, people with CD4 nadirs below 350 cells/mm³ had 1.22% lower FMD compared to those with higher nadirs, a statistically significant difference.
• Current CD4 cell count, however, showed little association with FMD.

"Among treated HIV-infected individuals, nadir CD4 T-cell count less than 350  [cells/mm³] is independently associated with lower FMD, suggesting that delayed therapy results in sustained harm to endothelial function," the study investigators concluded. "Our data support future prospective studies evaluating cardiovascular effects of [combination ART] initiation at higher CD4 cell counts."

In their discussion, the authors noted that the reduction in FMD associated with nadir CD4 count below 350 cells/mm³ was greater than the reduction associated with traditional cardiovascular risk factors such as smoking and diabetes.

6/5/12

Reference

JE Ho, R Scherzer, FM Hecht, et al. The association of CD4+ T-cell counts and cardiovascular risk in treated HIV disease. AIDS 26(9):1115-1120. June 1, 2012.