People with HIV have an increased risk of
cardiovascular disease, and the risk is higher still for those taking
antiretroviral therapy, results of a meta-analysis published in HIV Medicine show.
Overall, infection with HIV increased the
relative risk of cardiovascular disease by 61%, and the risk was doubled for
those taking HIV treatment. The risk differed between classes of
antiretrovirals and specific anti-HIV drugs.
However, most of the increased risk was due
to higher rates of coronary heart disease (CHD). The investigators note that
this “refers to atherosclerosis of the coronary arteries. It is important to
note this distinction from other manifestations of CVD [cardiovascular
disease], especially as there is less evidence on the impact of ART associated
with other CVD events than CHD.” Moreover, the majority of cardiovascular
events associated with HIV treatment “were confined to patients who were
already at increased risk of CVD”.
Cardiovascular disease is an increasingly
important cause of death in people with HIV. There is no consensus about the
reasons for this, especially the role of antiretroviral therapy.
Because of this lack of certainty,
investigators from Sydney, Australia, conducted a systematic review and
meta-analysis of studies comparing the risk of cardiovascular disease between
HIV-positive and HIV-negative individuals; studies comparing the risk between
people taking antiretroviral therapy and those who were treatment naive;
research comparing the risk between classes of antiretroviral drugs; and
studies exploring the association between specific drugs and the risk of
Observational studies and
randomised-controlled trials involving adults, conducted before August 2010, were
eligible for inclusion in the analysis. Cardiovascular disease was defined as
heart attack, ischaemic heart disease, cardiovascular and cerebrovascular
events and coronary heart disease.
A total of 23 studies, including two
randomised-controlled trials, met the investigators’ inclusion criteria.
Three studies looked at the overall
cardiovascular risk of HIV-positive people. Their pooled results showed that,
compared to HIV-uninfected controls, HIV-positive people had a higher
relative risk of cardiovascular disease (RR = 1.61; 95% CI, 1.43-1.81; < 0.001).
A further three studies compared risk
between people taking antiretroviral therapy and HIV-negative controls. Their
pooled results showed that participants taking HIV treatment had twice the relative
risk of cardiovascular disease (RR = 2.00; 95% CI, 1.70-2.37; p < 0.001).
“In summary,” comment the investigators, “the risk of CVD is two times higher
among ART-treated PLHIV [people living with HIV] than HIV-uninfected people.”
The results of eight studies were used to
compare the risk of heart disease for people taking HIV therapy compared to
HIV-positive study participants who were treatment naive. Their pooled results showed that
treatment-experienced participants had an increased risk (RR = 1.52; 95% CI,
1.35-1.70; p = 0.001). “PLHIV who are on ART have a 52% higher risk of CVD
compared with PLHIV unexposed to any ART,” comment the authors.
Next, they compared the risk of
cardiovascular disease between people taking each of the three main classes
of antiretrovirals and treatment-naive patients.
Analysis of specific NRTIs showed
that abacavir (Ziagen, also in Kivexa), non-abacavir and ddI (Videx)-containing regimens were all
associated with an increase in risk (all p < 0.001).
Risk was also compared between types of HIV
Pooled results of four studies showed that
treatment containing a protease inhibitor resulted in a higher risk of
cardiovascular disease than non-protease inhibitor regimens (RR = 1.41; 95% CI, 1.21-1.65;
p < 0.001).
Duration of treatment was also an important
risk factor. Each year of therapy with a protease inhibitor increased the risk
by 11% (RR = 1.01-1.10) and each additional year of treatment with NRTIs was
associated with a 5% increase in risk (RR = 1.05; 95% CI, 1.01-1.10).
Cumulative exposure to specific anti-HIV
drugs also increased the risk. Each year of therapy with the protease inhibitor
increased the relative risk by almost a fifth (RR = 1.19; 95% CI, 1.03-1.39; p
= 0.022), whereas each year of therapy with abacavir was associated with a 9%
increase in risk (RR = 1.05; 95% CI, 1.02-1.16).
The investigators stress that it is
important to place their results within wider contexts and to understand
potential confounders. “Despite being a risk factor for CVD, ART use has
increased the quality and length of life of PLHIV…it is possible that the use
of ART increases life expectancy and hence increases the average age of those
taking ART in comparison to the reference group, which may lead to confounding
They conclude: “The reasons for the excess
risk of CVD among HIV-infected people are not very well known and require
considerable attention as CVD is likely to be on of the major conditions to be
confronted in the future by populations of PLHIV.”