US research published
in the online edition of Clinical
Infectious Diseases suggests that both uncontrolled HIV replication and therapy with some types of
antiretroviral drug contribute to hardening of the arteries, an important early
warning sign of cardiovascular disease.
Investigators from the
Study to Understand the Natural History of HIV/AIDS in the Era of Effective
Therapy (the SUN study), found that suppressing viral load to undetectable
levels lessened the progression of atherosclerosis. Patients whose HIV therapy
included a non-nucleoside reverse transcriptase inhibitor (NNRTI) were less
likely than those who received a protease inhibitor to experience hardening of
“Our findings suggest
that maintaining a clinically suppressed VL [viral load] protects against
atherosclerotic progression,” comment the authors. “After adjusting for the
protective effects of viral suppression, use of NNRTI-based cART [combination
antiretroviral therapy] was associated with less [hardening of the arteries]
than was PI-based cART.”
is now an important cause of illness and death in patients with HIV. The exact
reasons are unclear but appear to include a number of factors. These include
the ageing of the HIV population and the high prevalence of traditional risk
factors, for example smoking.
However, some research
has suggested that uncontrolled HIV replication may be an important risk
factor. This is probably related to the inflammatory effects of the virus.
taking antiretroviral therapy have a lower risk of cardiovascular disease than
individuals not taking anti-HIV drugs. But, studies have suggested that
protease inhibitors increase the risk of cardiovascular disease. There is also
controversy about the risk of heart attack associated with abacavir (Ziagen, also in the combination pill Kivexa).
Researchers from the
SUN study wanted to clarify the causes of cardiovascular disease in patients
early-warning sign of cardiovascular disease is hardening of the carotid
artery. Therefore the investigators monitored the carotid artery intima-media
thickness (CIMT) of 389 HIV-positive patients over a two-year period. The
patients were recruited between 2004 and 2006.
At baseline the
patients had a median age of 42 years, and 77% were men. A third of patients
were smokers and 36% had a diagnosis of hypertension when they entered the
The median baseline
CD4 cell count was 485 cells/mm3 and 78% of patients were taking HIV
therapy. At the start of the study, 88% of the treated patients had an
undetectable viral load and 61% maintained a viral load below the limit of
detection for the two years of the research.
Similar proportions of
patients were taking NNRTI-based and PI-based HIV therapy. Approximately a
quarter of patients were taking abacavir and 36% were prescribed tenofovir (Viread, also in the combination pills Truvada and Atripla).
Median CIMT at baseline
was 0.707 mm and this increased to 0.721 mm after two years. The median
two-year change of 0.016 mm was significant (p < 0.001).
Less CIMT progression
was seen in patients who were prescribed HIV therapy at baseline than in those
who were not (0.014 mm vs. 0.019 mm) and in patients with a suppressed baseline
viral load (0.013mm vs. 0.021 mm). These differences approached significance.
investigators found that patients who maintained an undetectable viral load
throughout the two years of the study had less CIMT progression than patients
with detectable virus (0.015 mm vs. 0.019 mm, p < 0.001).
CIMT progression was
also less in those prescribed an NNRTI than in those taking a protease
inhibitor (0.011mm vs. 0.019 mm, p = 0.012).
first analysis showed that a higher body mass index was
associated with hardening of the arteries (p < 0.01), as was poorer kidney
function (p = 0.029), a persistently detectable viral load (p = 0.023) and
treatment with a protease inhibitor (p = 0.004).
Further analysis controlled for
potentially confounding factors. This showed that a detectable viral load at
baseline (p = 0.015) and during follow-up (p < 0.001) both remained
associated with CIMT progression, as did a higher body mass index (p <
HIV replication is associated with greater CIMT,” comment the authors.
Analysis was then
restricted to the patients taking HIV therapy.
After adjusting for
traditional risk factors and HIV suppression during follow-up, the
investigators found that therapy with a protease inhibitor was associated with
more extensive hardening of the arteries than treatment based on an NNRTI (p =
persisted when the analysis only included individuals who did not switch
between NNRTIs and protease inhibitors during the course of the study (p =
There was no evidence
that abacavir increased the risk of CIMT progression.
implicating PI exposure are consistent with data from the D:A:D study,” write
the investigators, “but we observed no differences in CIMT progression between
abacavir and tenofovir.”
“Persistent suppression of HIV replication below clinical thresholds was
associated with less atherosclerotic progression. Future controlled studies are
needed to replicate these findings and better characterise the proatherogenic
mechanisms of HIV replication as well as evaluate the net benefit of specific
antiretrovirals on long-term CVD risk.”