US researchers have found that thickening of the carotid artery in patients with HIV appears to be associated with traditional risk factors, rather than those connected with either the severity of HIV disease or the use of antiretroviral therapy. However, in a study published in the online edition of AIDS, the investigators report that treatment with tenofovir had a protective effect against thickening of this artery.
“Traditional risk factors are more important in predicting levels of cIMT [carotid-intima media thickness] in HIV infection,” comment the investigators.
The life expectancy of patients with HIV has improved dramatically since the introduction of effective antiretroviral therapy and is now considered likely to be of near-normal duration.
However, increased rates of cardiovascular disease have been observed in patients with HIV. The exact reasons for this are unclear, but possible reasons include a high prevalence of traditional risk factors, the inflammatory effect of HIV disease, and the side-effects of anti-HIV drugs.
An important early warning sign of increased risk of cardiovascular risk is increased thickness of the carotid artery.
Therefore, investigators from the US Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) measured carotid-intima media thickness in 538 patients and then conducted analyses to see if increased thickness was due to traditional or HIV-related risk factors.
Using an ultrasound, thickness of the carotid artery was assessed in three locations: common; internal; and bulb.
A method of statistical analysis called Bayesian model averaging was used to calculate which factors were associated with carotid-intima media thickness. The investigators believed that this form of analysis was especially appropriate for use in an observational study.
The patients had an average age of 48 years, 69% were men and 41% were African Americans. The average common carotid-intima media thickness was 0.88 mm, with average internal carotid-intima media thickness being 1.16 mm.
Nearly all the patients (94%) had experience of antiretroviral therapy.
Factors with a 50% probability of being associated with carotid-intima media thickness were considered potentially significant and carried over into subsequent analysis.
For common carotid-intima media thickness these factors were: age; African American or Hispanic race (100% probability); blood pressure (systolic, 97% probability; diastolic, 95% probability; HDL cholesterol (85% probability); and treatment with tenofovir (51% probability of lower carotid-intima media thickness).
The risk factors associated with internal carotid-intima media thickness were age (100% probability) and smoking.
Further analysis confirmed that each year of treatment with tenofovir was associated with a reduction in common carotid-intima media thickness of a significant 0.009 mm (p = 0.0278).
Treatment with this drug was the only HIV-related factor with any association with thickness of the carotid artery.
“We did not find evidence of an association between markers of HIV disease severity or most antiretroviral drugs or classes and cIMT,” comment the investigators. However, they comment, “we are not able to rule out modest effects of HIV-related factors with the data available.”
The investigators were uncertain why treatment with tenofovir was associated with lower carotid-intima media thickness. Patients who had received treatment with tenofovir had a similar demographic profile to individuals who had received other antiretroviral drugs. Moreover, traditional cardiovascular risk factors were also comparable.
However, patients taking tenofovir had lower total cholesterol (p = 004).
But the investigators also found some evidence that patients taking tenofovir may have had more severe HIV disease in the past. Their nadir CD4 cell counts were significantly lower (p < 0.01), and they were more likely to have progressed to AIDS (p < 0.01). In these circumstances, the investigators find “the inverse association of tenofovir use and cIMT counterintuitive”.
They suggest “further research on the properties of tenofovir, especially randomized trials, will be required to see if this novel finding is replicated”.
In the meantime, the investigators believe that their research “may indicate that we need to examine HIV-infected cohorts at earlier stages of infection to understand the pathophysiology of vascular disease in those with HIV infection.”
Delaney JAC et al. Associations of antiretroviral drug use and HIV-specific risk factors with carotid intima-media thickness. AIDS 24: online edition, DOI: 10.1097/QAD. Obo13e32833d2132, 2010.