People with HIV had
higher mortality than HIV-negative individuals after hospitalisation for acute
coronary syndrome, but the excess risk disappeared for people on
antiretroviral therapy with high CD4 cell counts, researchers reported last
week at the IDWeek 2013 conference in San Francisco.
People with HIV are at higher risk for cardiovascular disease,
but whether this is due to the virus itself, resulting inflammatory and
metabolic changes, antiretroviral toxicities or other factors is not yet fully
studies have looked at outcomes amongst people with HIV following acute
coronary syndrome (ACS), which includes heart attacks (myocardial infarction),
unstable angina (chest pains) and other conditions caused by blockage of blood vessels
supplying the heart muscle.
Silverberg and colleagues with Kaiser Permanente, a large managed-care organisation
in the US, asked whether HIV status, immune deficiency or antiretroviral
therapy (ART) use affects long-term survival following ACS hospitalisation. The
Kaiser team previously reported that HIV-positive people had a 40 to 50% higher
risk of myocardial infarction compared with HIV-negative people seen at their
analysis included all patients hospitalised for the first time with ACS at
Kaiser Permanente Northern California between 1996 and 2010. Of these, 226 were
HIV positive and 86,321 were HIV negative. Silverberg noted that, in the San Francisco
area, more than half the population of people with HIV are now over 50 years of
were included if they had ST-elevation myocardial infarction (STEMI) –
typically the more severe type, non-ST myocardial infarction (NSTEMI) or
unstable angina. Deaths were determined based on hospital
records, California death certificates and Social Security Administration
patients were more likely than their HIV-negative counterparts to be men (94
vs 63%, respectively) and were younger on average (54 vs 67 years). Within the
HIV-positive group, 75% were white, 17% were black and 9% were Hispanic, Asian
or 'other'; in the HIV-negative group the corresponding percentages were 78,
8 and 15%.
Amongst people with HIV,
58% were taking protease inhibitor-based ART, 26% were on protease-sparing ART
and 16% were not on ART. About 20% had CD4 counts under 200 cells/mm3,
nearly half had counts between 200 and 499 cells/mm3 and one-third had counts above 500
People with HIV were
more likely to be hospitalised with STEMI (37 vs 25%), both groups were
equally likely to have NSTEMI (about 33%) and HIV-negative patients were more
likely to have unstable angina (28 vs 42%).
About 13% in both groups
had elevated LDL or 'bad' cholesterol, but the HIV-positive group was significantly
more likely to have low HDL or 'good' cholesterol (59 vs 40%) and elevated
triglycerides (73 vs 50%). People with HIV were also significantly more likely
to be current or former smokers (70 vs 55%).
Absolute all-cause mortality
rates at one and three years after an ACS diagnosis were similar – actually a
bit lower – in the HIV-positive group compared with the HIV-negative group: 7.6
vs 9.8% at one year and 16.6 vs 18.6% at three years.
However, after adjusting
for confounding factors including age, sex, race, ACS type, blood lipid levels
and smoking, the HIV-positive group had a significantly greater hazard of death.
Adjusted hazard ratios were 2.2 at one year and 2.5 at three years, or more
than twice the risk of death.
Comparing the different
CD4 cell levels, absolute three-year mortality rates were 29.8, 17.9 and 4.9%
for HIV-positive people with less than 200 cells/mm3, 200 to 499
cells/mm3 and more than 500 cells/mm3, respectively.
After adjusting for confounders, people with 200 to 499 cells/mm3 had a
three-year adjusted hazard ratio of 2.5 relative to HIV-negative people – the
same as the HIV-positive group as a whole. Those with under 200 cells/mm3
had substantially higher mortality, with an adjusted hazard ratio of 5.6, or more
than a five-fold increase. On the other hand, people with CD4 counts above 500
cells/mm3 had a slightly lower risk of death (adjusted hazard ratio
0.7 relative to HIV-negative patients), though this difference was not
antiretroviral treatment, HIV-positive people who were not on ART had the
greatest absolute risk of death at 22.0%, compared with 16.9 and 12.1% for
those on protease inhibitor-based and protease-sparing regimens, respectively.
Untreated individuals had an adjusted hazard ratio of 3.4 relative to the HIV-negative
group, or triple the risk of death. Adjusted hazard ratios for patients taking protease
and non-protease regimens were 2.5 and 1.8, respectively, the latter of which
was not significantly different from HIV-negative patients. However, when
comparing protease-based and protease-sparing regimens directly, the difference
in mortality between them did not reach statistical significance.
"HIV patients, in adjusted models, had higher
all-cause mortality at one and three years after an ACS hospitalisation," the researchers
summarised. There was "no mortality difference at three years for
HIV-positive ACS patients with CD4 >500 compared with HIV-negative
As a limitation of their
study, they noted that they did not look at cause-specific mortality – so they
could not determine how many died of cardiovascular-related causes – and they
did not account for treatments such as revascularisation surgery or cardiac
that it was hard to separate the effects of CD4 cell count and ART use in
this analysis, and he said numbers were too small to see if there was a
difference in ACS outcomes amongst people who took abacavir (Ziagen), which has been linked to heart
attacks in some but not all studies.
observed higher mortality after an ACS hospitalization for HIV patients appears
to be driven by HIV-related factors, including low CD4 and lack of ART
use," the investigators concluded. "These results strengthen
recommendations for earlier initiation of ART."
In response to an audience question, however, Silverberg said there were
not enough people in the study to address the current controversy as to whether
ART use is beneficial amongst those with CD4 cell counts of more than 500 cells/mm3.