Can an Alzheimer’s Drug Help HIV+ People with Cognitive Dysfunction?

CROI 2012 Paper #482.  Rivastigmine for the Treatment of
HIV-associated Neurocognitive Disorders: A Randomized, Double-blind,
Placebo-controlled, Crossover Pilot Study
The prevalence of
HIV-associated neurocognitive disorders (HAND) remains high despite successful
antiretroviral therapy.  This study
performed by researchers from the HIV Swiss Cohort aimed at looking at the
effect of rivastigmine on HAND in patients with undetectable HIV viral load in
blood and cerebrospinal fluid but who had symptoms of neurocognitive
Rivastigmine (sold
under the trade name Exelon) is an approved agent used in  the treatment of mild to moderate dementia of
the Alzheimer’s type and dementia due to Parkinson’s disease.
 This was a 2-site, randomized, double-blind,
placebo-controlled, crossover study in 17 HIV+ patients (12 men, mean 54.7
years old, 660  CD4+) with HAND. All
patients had undetectable viremia in both plasma and cerebrospinal fluid at
study entry, and no lesions on brain MRI. Participants were randomized to
receive either rivastigmine by mouth (5 months) followed by identical placebo (5
months) after a 6-week wash-out period, or placebo followed by rivastigmine .
Dosage was progressively increased from 1 mg to reach 12 mg per day of
rivastigmine. Four study visits included neuropsychological examinations. The
primary outcome was the Alzheimer’s Disease Assessment Scale-Cognitive Subscale
(ADAS-Cog). Secondary endpoints were 8 cognitive measures of attention,
information processing speed, working memory and executive functioning, as well
as perceived quality of life (MOS-HIV). The difference between start/end values
during each 5-month study period was used as a combined outcome for each
Rivastigmine induced
mild to moderate adverse events in 9 patients that disappeared after slight
dose reduction. Four patients withdraw because of severe nausea,
nightmares/anxiety, and allergic reactions. One measure of attention/processing
speed improved on drug (Trail Making Test A). Executive functioning also
improved but did not reach statistical significance due to the small sample
size (CANTAB Spatial Working Memory). Patients showed a trend for a
self-reported enhanced cognitive functioning (MOS-HIV) on drug . There was no
significant improvement on the ADAS-Cog.
In small trials, drug
effects need to be very large to reach statistical significance. This pilot
study suggests that the use of rivastigmine in aviremic HIV+ patients with HAND
may improve cognitive functions that are typically affected in HAND, i.e.,
information processing speed and executive functioning.
This study used an
oral formulation.  It is known that a
transdermal patch formulation has been better tolerated in Alzheimer’s
patients, so it will be interesting to test this drug in a patch form in a
larger group of patients with HAND who have undetectable viral load.

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