people who are taking antiretroviral therapy (ART) and are hospitalised due to
heart failure are more likely to die because of cardiovascular disease if they
are taking a regimen containing a protease inhibitor, according to research
conducted in the United States and published in the Journal of the American College of Cardiology.
hospital readmission rates were twice as high among people taking a protease
inhibitor (PI) compared to a non-protease inhibitor (NPI) regimen. The relationship
between PI therapy and these adverse outcomes remained
significant after controlling for other risk factors.
“To our knowledge,
these findings are the first data linking PI-based ART to adverse structural
changes and outcomes among PWHIV [people with HIV] with HF [heart failure],”
comment the researchers.
But the authors of
an accompanying editorial are not convinced. They note that many of the
patients had ongoing HIV replication despite taking antiretrovirals, and they
suggest this could have been a cause of cardiovascular death.
Thanks to ART, most HIV-positive people have an excellent life
expectancy. The diseases of ageing, including cardiovascular disease, are now
an important cause of serious illness and death among HIV-positive people.
Heart failure occurs when the heart is unable to pump blood, because of damage to valves or muscles in the heart, or prolonged high blood pressure, or because of congestion in the arteries that supply the heart. The condition is progressive without treatment.
Treatment with PIs has been associated with adverse changes in cardiac
structure and an increased risk of cardiovascular events. Investigators at the
Mount Sinai Hospital in the Bronx wanted to see if PI treatment
was associated with adverse cardiovascular outcomes among HIV-positive people
hospitalised because of heart failure.
designed a retrospective study involving all antiretroviral-treated people
admitted to their hospital with heart failure in 2011. The patients were
stratified according to use of PI-containing and non-PI-containing regimens.
Data were collected on the baseline prevalence of cardiovascular risk factors.
The investigators compared cardiovascular mortality, and readmission due to
heart failure within 30 days according to use of PI and non-PI regimens.
population consisted of 394 people. The median duration of ART was 8.5 years. Mean CD4 cell count was 295 cells/mm3 and
median viral load was 274 copies/ml. Almost half (48%) of people had a
detectable viral load (above 200 copies/ml). The mean age was 60 years and 47%
of the sample were female.
Just over a third
(37%) were taking a PI-containing regimen and 67% were taking a non-PI
combination. All the PI regimens were ritonavir boosted.
PIs had a higher prevalence of several cardiovascular risk factors than
individuals treated with alternative regimens, including hyperlipidemia (52%
vs 35%, p < 0.001), diabetes mellitus (44% vs 31%, p = 0.012), coronary
artery disease (52% vs 33%, p < 0.001), higher pulmonary artery pressure
(PASP) (p < 0.001) and lower left ventricular ejection fraction (LVEF) (p =
During two years
of follow-up, 23% of people died because of a cardiovascular cause. Cardiovascular mortality was 35% among people who were taking a PI at the
time of their hospital admission with heart failure and 17% among people
taking a non-PI regimen at the time of their admission. This difference was
highly significant (p < 0.001).
Rates of hospital
readmission due to heart failure within 30 days were also significantly higher
among PI-treated people than non-PI-treated people (68% vs 34%, p < 0.001).
for other risk factors, PI therapy was associated with an almost twofold
increase in the risk of cardiovascular mortality (HR = 1.797; 95% CI, 1.257-2.567,
p = 0.001). A low CD4 cell count, abnormal cardiovascular structure and history
of coronary artery disease were also risk factors.
is needed to determine whether PI-based regimens, either individual regimens or
as a class effect, contribute pathophysiologically to processes leading to
worse outcomes in HF…and whether these findings can be replicated in
prospective cohorts,” conclude the investigators.
authors of an accompanying editorial believe the study’s findings are far from definitive.
They believe the
results are “intriguing” but also note that a very high proportion of people
had ongoing HIV replication and that the investigators did not present data on
medication adherence, one of many limitations they highlight in the study
“We suggest that immune dysregulation and inflammation are also
plausible mechanisms for the higher mortality seen in PHIV,” they write. “Data
on medication adherence and viral suppression should be carefully collected
because not only is medication adherence an important predictor of health
outcomes among PHIV, but also differences by drug class may serve as important
confounders for cardiovascular endpoints.”