Despite a new analysis of data from the Fat Redistribution and Metabolic Change in HIV (FRAM) study, it’s still unclear which HIV-specific factors—HIV infection itself or the antiretrovirals (ARVs) used to treat it—contribute to an increased risk of heart disease in people living with the virus. Interestingly, the FRAM report, published online July 27 in the journal AIDS, stated that tenofovir—found in Viread, Truvada and Atripla—appears to be modestly associated with a lower risk of carotid artery thickness, a predictor of cardiovascular disease (CVD).

Numerous studies have shown that people with HIV have a higher risk than their HIV-negative counterparts of developing CVD, especially heart attacks. When researchers have tried to pinpoint the specific characteristics that would explain this increased risk, however, different studies have yielded different results. While most studies find at least some evidence that traditional CVD risk factors are partially to blame—such as smoking, age, hypertension and diabetes—other studies have found that HIV itself, and ARVs, might also contribute.

To determine the influence of a variety of risk factors on CVD risk in people with HIV, Joseph Delaney, PhD, from the University of Florida in Gainesville, and his colleagues examined the medical record of 538 FRAM participants who had at least one ultrasound measurement of the thickness of the carotid artery—called carotid-intima media thickness (cIMT)—taken during the course of the study. The thicker the walls of a person’s carotid arteries, located on both sides of the neck, the greater his or her risk of developing CVD.

The average age of the FRAM participants at the time of the cIMT scan was 48, and the estimated duration of HIV infection was 13 years. About 70 percent of the participants were male, 40 percent were African American, and more than half were current or former smokers. Nearly all had been on ARV therapy.

Delaney and his colleagues found that some traditional CVD risk factors—such as age, smoking history and race—were associated with greater cIMT thickness, while others—such as cholesterol levels and blood pressure—were not. Similarly, the findings on CVD risk from HIV-related characteristics were mixed.

Several previous studies have shown an increased CVD risk in people with very low CD4s or high viral loads and people on protease inhibitors. In this study, those factors did not predict an increased cIMT. The authors explain, however, that because people in the FRAM study have been infected for so much longer than in other similar studies, any additional CVD risk from protease inhibitors, low CD4s or high viral load may have evened out over time. Also, because Delaney’s team didn’t have participants’ cIMT measurements from before they became infected or before they started ARVs, it is difficult to interpret these results too broadly.

As for tenofovir, it was the only HIV-related characteristic that was at all associated with cIMT—and the association was actually inverse—meaning that the longer a person took tenofovir, the less likely he or she was to have thicker carotid arteries.

Delaney and his coauthors caution that the association was modest, and that there might have been characteristics about tenofovir users that would explain their lower risk for having thicker carotid arteries. Previous studies have also suggested a cardio-protective effect from tenofovir, including the possibility that it lowers low-density lipoprotein (LDL) cholesterol.

Future studies that measure cIMT in people who are randomly assigned to take tenofovir or another drug would be needed, said the authors, to solidly confirm their findings.

The authors concluded that their study wasn’t able to provide an explanation for increased CVD in people with HIV. They hypothesized that future studies, which include people earlier in HIV disease and follow them over longer periods of time, might help characterize why people with HIV appear to have greater CVD risks than similar HIV-negative people.