 | HIV
and Hepatitis.com
Coverage of
the 13th Annual Conference on Retroviruses and Opportunistic Infections February 5 - 8, 2006, Denver, CO |
Protease Inhibitor
Therapy Increases
Risk of Myocardial
Infarction:
D:A:D Study
Prior
data from the
D:A:D study
demonstrated
a progressive
increase in
the risk of
myocardial
infarction (MI)
with longer
exposure to
combination
antiretroviral
therapy (cART).
In a study presented
at the 13th
CROI, the D:A:D
investigators
evaluated if
the association
between cART
and MI differed
by drug class
and possible
mechanisms for
the association.
D:A:D
is an observational
study of 23,400+
HIV-infected
patients from
11 cohorts in
Europe, Australia
and USA. The
results of the
analysis were
based on follow-up
to February
2005, by which
time 345 patients
experienced
an MI over 94,469
PY (3.65/1000
PY). Increased
time on cART
was associated
with a risk
of MI (adjusted
RR 1.16/year
of exposure
[95% CI: 1.09-1.23]),
but the risk
has decreased
over calendar
time (RR for
2003/4 vs. 1999:
0.50 [0.32-0.77]);
however, this
difference is
lost following
adjustment for
latest lipid
levels
(RR for 2003/4
vs 1999: 0.82
[0.49-1.37]).
Total
exposure to
the PI drug
class was 72,846
PY (30,198 PY
in patients
with no NNRTI
exposure)
and to the NNRTI
drug class 52,457
PY (9,808 PY
in patients
with no PI exposure).
MI incidence
increased from
1.53/1000 PY
in those not
exposed to PIs
to 6.01/1000
PY in those
exposed for
>6 years
(RR/year of
exposure: 1.17
[1.12-1.23]).
The
incidence also
increased slightly
with NNRTI exposure
(RR/year: 1.07
[1.00-1.14]).
After adjustment
for the other
drug class and
other known
risk factors
for MI, the
relative rate
per year of
PI exposure
was 1.16 ([1.10-1.23],
p=0.0001), while
for NNRTIs it
was 1.05 ([0.98-1.13],
p=0.17). These
associations
persisted, although
were reduced
slightly, after
controlling
for years of
NRTI use. Total
cholesterol
(1.24/mmol/L
[1.14-1.34]),
HDL
cholesterol
(0.76/mmol/L
[0.53-1.08]),
and triglycerides
(1.42/doubling
[0.85-2.38])
were associated
with the risk
of MI; adjustment
for these reduced
the effect of
PI and NNRTI
exposure to
1.10 [1.03-1.17]
and 1.01 [0.93-1.10],
respectively. The
authors conclude,
“Increased PI
exposure is
associated with
an increased
risk of MI,
which is partly
explained by
dyslipidemia.
Conversely,
although there
were fewer years
of experience,
we found no
evidence that
increased NNRTI
exposure is
associated with
risk of MI.” 02/10/06 Reference
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