Key
Takeaways
-
Women
with
HIV
are
more
susceptible
to
stress-related
cognitive
impairments
such
as
memory
and
verbal
learning
deficits. -
In
a
randomized
trial
of
women
with
virally
suppressed
HIV,
low-dose
hydrocortisone
significantly
improved
learning
scores
at
4
hours
after
dosing,
as
well
as
attention
scores
at
30
minutes
and
4
hours,
compared
with
placebo. -
Women
who
took
low-dose
hydrocortisone
daily
for
4
weeks
had
a
significantly
greater
improvement
in
delayed
recall
versus
the
placebo
group,
but
the
treatment
×
time
interaction
was
not
significant.
Low-dose
hydrocortisone
(LDH)
improved
aspects
of
cognition
in
women
with
virally
suppressed
HIV,
a
randomized
trial
showed.
In
the
first
phase
of
the
two-phase
study,
women
who
received
a
single
10-mg
dose
of
oral
LDH
had
significantly
improved
learning
scores
at
4
hours
after
dosing
(Cohen’s
d=0.35,
P=0.03),
as
well
as
significantly
better
attention
scores
at
30
minutes
(Cohen’s
d=0.38,
P=0.02)
and
4
hours
(Cohen’s
d=0.42,
P=0.01),
compared
with
those
in
the
placebo
group.
However,
there
were
no
significant
treatment
effects
for
working
memory,
visuospatial
abilities,
or
executive
function,
reported
Leah
Rubin,
PhD,
MPH,
of
Johns
Hopkins
University
in
Baltimore,
and
colleagues
in
JAMA
Network
Open.
In
the
trial’s
second
phase,
women
who
took
10-mg
LDH
daily
for
4
weeks
had
a
significantly
greater
improvement
in
delayed
recall
versus
the
placebo
group
(Cohen’s
d=0.71,
P=0.005),
but
the
treatment
×
time
interaction
was
not
significant
(Cohen’s
d=0.42,
P=0.22).
Both
the
LDH
and
placebo
groups
had
improvements
in
executive
function,
though
there
were
no
significant
treatment
effects
for
total
learning,
working
memory,
or
attention
in
either
group.
“These
findings
support
the
potential
clinical
relevance
of
the
observed
cognitive
effects
while
also
highlighting
variability
in
treatment
response
and
the
need
to
identify
characteristics
associated
with
treatment
responsiveness,”
Rubin
and
colleagues
wrote.
Dysregulation
of
the
hypothalamic-pituitary-adrenal
(HPA)
axis
is
tied
to
chronic
stress,
psychiatric
symptoms,
and
cognitive
impairment.
Women
with
HIV
are
more
susceptible
to
stress-related
cognitive
impairments
such
as
memory
and
verbal
learning
deficits.
The
trial’s
results
suggest
that
“transient
modulation
of
the
HPA
axis
can
enhance
domain-specific
cognitive
function,
particularly
verbal
learning,
memory,
and
attention,
in
populations
affected
by
chronic
stressors,
psychiatric
comorbidities,
and
cognitive
impairment,”
the
authors
noted.
While
LDH
was
linked
to
some
cognitive
improvements,
the
corticosteroid
is
likely
a
therapeutic
means,
not
an
end.
The
findings
support
LDH
“primarily
as
a
mechanistic
or
proof-of-concept
intervention
targeting
stress-system
dysregulation
rather
than
as
a
long-term
corticosteroid
treatment
strategy,”
Rubin
and
team
pointed
out.
Conducted
between
November
2017
and
July
2023,
the
two-phase,
double-blind
trial
randomized
81
women
with
virally
suppressed
HIV
to
either
LDH
or
placebo.
In
the
trial’s
first
phase,
74
women
received
either
a
single
dose
of
10-mg
LDH
or
placebo
and
were
analyzed
at
30
minutes
and
4
hours
after
dosing.
In
the
second
phase,
72
women
took
either
10-mg
LDH
daily
or
placebo
for
4
weeks.
Participants
had
elevated
self-reported
stress,
mood
or
anxiety
disorder,
or
both,
and
objective
impairment
in
at
least
one
cognitive
domain.
Mean
age
was
55.2
years,
90.1%
were
Black
or
African
American,
and
4.9%
were
white.
Median
HIV
infection
duration
was
20
years,
and
84.2%
had
an
undetectable
viral
load.
Most
women
had
memory
impairment
(71.6%)
or
learning
impairment
(50.6%).
The
study’s
primary
outcomes
were
verbal
learning
and
memory
(assessed
with
the
Hopkins
Verbal
Learning
Test-Revised),
working
memory
(assessed
with
the
Letter-Number
Sequencing
task),
and
visuospatial
abilities
(assessed
with
the
Repeatable
Battery
for
the
Assessment
of
Neuropsychological
Status
Line
Orientation
subtest).
Secondary
outcomes
included
attention
and
executive
function,
as
well
as
mechanistic
markers,
such
as
salivary
cortisol.
In
the
intervention
arm,
LDH
produced
a
cortisol
increase
peaking
75
minutes
post
dose
(Cohen’s
d=1.30,
P<0.001).
Four
weeks
of
LDH
therapy
was
linked
to
no
serious
adverse
events,
nor
were
there
clinically
meaningful
changes
to
patients’
metabolic,
hepatic,
kidney,
cardiovascular,
or
HIV-related
markers.
The
most
common
adverse
events
were
sleep-related
symptoms
and
changes
in
energy
or
fatigue,
which
occurred
with
similar
frequency
in
the
LDH
and
placebo
groups.
Limitations
included
the
study’s
small
size,
which
left
it
underpowered
to
detect
acute
and
sustained
effects
on
cognition
with
LDH.
The
study’s
size
also
precluded
identification
of
LDH
response
modifiers,
including
the
impact
of
stress
burden
or
psychiatric
symptoms
on
treatment-related
cognitive
changes.
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