| Authors: Letendre S, Bharti A, Perez Valero I, Landay A, Hanson, Franklin D, Woods S, Heaton R, Grant I, Lurain N, for the CHARTER Group |
| Abstract:Background:
In
people
without
HIV,
CMV
reactivation
occurs
more
frequently
with
advancing
age
and
is
associated
with
immune
senescence,
inflammation,
cognitive
impairment,
and
earlier
mortality.
People
with
HIV
disease
are
nearly
universally
infected
with
CMV
and
maintain
high
levels
of
CMV-‐specific
T-‐cells,
even
during
antiretroviral
therapy
(ART).
We
measured
CMV
antibody
(Ab)
concentrations
in
138
HIV+
subjects
to
determine
their
associations
with
demographic,
disease,
and
NC
characteristics.
Methods:
138
subjects
were
selected
from
882
who
enrolled
in
the
CHARTER
project
and
had
one
assessment.
Subjects
with
severe
neurocognitive
comorbidities
were
excluded.
CMV
Ab
concentrations
were
measured
by
enzyme-‐linked
immunosorbent
assay.
NC
functioning
was
determined
by
standardized
comprehensive
testing
and
was
summarized
by
the
global
deficit
score
(GDS)
method.
Analyses
were
performed
using
routine
univariable
and
multivariable
regression
methods.
Results:
The
selected
subjects
were
mostly
middle-‐aged
(median
43
years)
men
(81%)
without
AIDS
(51%)
who
were
taking
ART
(67%)
and
had
global
NC
impairment
(58%).
Among
those
taking
ART,
HIV
RNA
was
undetectable
in
58%
of
plasma
and
82%
of
CSF
specimens.
Subjects
were
similar
to
the
other
744
subjects
except
that
they
were
more
likely
to
have
AIDS
and
had
lower
current
and
nadir
CD4+
cell
counts.
CMV
Ab
levels
ranged
from
3.96
to
46.1
U/mL
(median
24.1).
Higher
CMV
Ab
levels
were
associated
with
older
age
(r
=
0.23,
p
=
0.006),
lower
nadir
CD4+
cell
counts
(r
=
-‐0.34,
p
<
0.0001),
ART
use
(t
=
3.0,
p
=
0.004),
and
worse
GDS
(r
=
0.17,
p
=
0.04).
Among
subjects
who
were
not
taking
ART,
higher
CMV
Ab
levels
were
also
associated
with
higher
HIV
RNA
levels
in
CSF
(r
=
0.29,
p
=
0.05)
but
not
in
plasma.
Multivariable
analysis
identified
that
worse
GDS
was
associated
with
higher
CMV
Ab
levels,
more
comorbid
conditions,
and
an
interaction
between
CMV
Ab
level
and
plasma
HIV
RNA
(R2
=
0.09,
p
=
0.02).
Analysis
of
the
interaction
identified
that
higher
CMV
Ab
levels
were
only
associated
with
worse
GDS
among
subjects
who
had
undetectable
HIV
RNA
in
plasma.
Conclusion:
Higher
CMV
antibody
levels
were
associated
with
worse
global
NC
functioning.
Together,
the
findings
have
implications
for
earlier
initiation
of
ART,
for
the
aging
of
the
HIV
population,
and
for
the
effect
of
CMV
on
HIV
in
the
central
nervous
system.
These
findings
add
to
existing
data
that
suggest
that
CMV
prophylaxis
may
be
beneficial. |