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
An important early warning sign of
increased risk of cardiovascular risk is increased thickness of the carotid
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.”