HIV infection, viral load and injecting drug use linked to early signs of cardiovascular disease

HIV-positive patients have signs of damage to the lining of blood vessels, according to a study published in the 1^st May edition of Clinical Infectious Diseases. The study found that blood vessel damage was more pronounced in the patients who had higher viral loads, particularly injection drug users.

Reduced flexibility of blood vessels in response to blood flow is the earliest detectable sign of the development of cardiovascular disease. This reduced flexibility, called ‘endothelial dysfunction’, is caused by the failure of cells lining blood vessels to stimulate the vessels to widen when blood flow increases.

Several studies have suggested that HIV-positive patients receiving antiretroviral therapy, particularly protease inhibitors, may be at risk of developing heart disease or strokes. To assess the effects of HIV infection and its treatment on endothelial function, investigators used ultrasound scans to measure the responses of a large artery in the arm in 75 HIV-positive patients from the Boston Medical Center Infectious Disease Clinic.

After constricting the blood flow through the arm with a blood pressure cuff for five minutes, the investigators measured the dilation of the brachial artery and blood flow after the cuff had been removed. They found that the dilation of the artery in the patients was significantly lower than in a group of 223 control patients from the same clinic (mean 7.3 vs. 11.1%, p

The difference between the two groups was similar when they adjusted the measurement for smoking, sex and body mass index (BMI), a measurement of body weight relative to height (p

Being a smoker, being male and having a BMI above 30 kg/m² were also independently linked to impaired endothelial function.

“The present study showed a strong association between HIV-1 infection and endothelial dysfunction,” write the investigators. “This finding is consistent with several studies that have described the association of coronary artery disease with HIV infection.”

Using a multivariate analysis, the investigators found that current injection drug use had a significant association with artery dilation in the HIV-positive patients (p = 0.007). Fifteen (20%) of the patients were current intravenous drug users, with seven using heroin, three using cocaine and five using both drugs.

The researchers noted that when they did not include injecting drug use in their calculations, HIV viral load emerged as being significantly associated with endothelial dysfunction (p = 0.04). This demonstrates that the effects of intravenous drug use on endothelial function may be caused by higher viral loads in the injecting drug users, possibly due to reduced adherence to their anti-HIV medication.

“Injection drug use (mainly cocaine use) is a well known risk factor for coronary artery disease,” the investigators explain. “At least part of the effect of current drug use is mediated by the HIV load. … Of note, twelve (80%) of the current drug users studied had viral loads that were not fully suppressed.”

Low levels of alpha-high-density lipoprotein triglyceride in the blood, a marker of disrupted fat metabolism, were also independently linked to endothelial dysfunction (p = 0.002). However, there were no differences between the patients who had been taking protease inhibitors for more than three months and those who had not, in contrast to previous studies.

“The role of metabolic abnormalities in HIV-infected patients receiving protease inhibitor therapy and the potential association of such abnormalities with accelerated cardiovascular and cerebrovascular disease in HIV-infected patients therefore [remains] controversial,” the investigators write.

The investigators confirmed that the differences in dilation of the blood vessels were due to the endothelial cells not working properly, by giving the patients a dose of the drug glyceryl trinitrate. This drug stimulates the blood vessels to dilate independently of the endothelial cells. Since it caused similar levels of dilation in the HIV-positive and control groups, the investigators concluded that the vessels were physically able to dilate, but problems with the endothelial cells were preventing dilation in response to blood flow.

The control subjects for this study were selected retrospectively from the clinic’s database of information on past patients. As they were not tested for HIV, the investigators could only presume that they were HIV-negative, casting some doubt on the study’s findings.

The study is also limited by its failure to take long-term diet and levels of exercise into account, and its use of a ‘surrogate’ marker of cardiovascular disease, which may not be directly associated with heart attacks or strokes in HIV-positive patients.

“Although HIV infection appears to be associated with substantial impairment of endothelial function, the degree to which this impairment translates into increased risk for cardiovascular disease in persons with HIV infection is still unknown,” the researchers write. “Prospective studies are needed to determine whether effective antiretroviral treatment can lead to improved endothelial function in HIV-infected persons.”