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OP 3.3
Neurocognitive Impairment in the HAART Era
Tozzi V, Balestra P, Vlassi C, Corpolongo A, Salvatori MF, Bellagamba R, Antinori A,
Narciso P
National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
There are three levels of HIV-related neurocognitive impairment (NCI): 1) Asymptomatic
NCI, with no decline in everyday functioning, 2) Mild Neurocognitive Disorder (MND), with
mild functional impairment, 3) HIV-dementia (HIV-D), with moderate to severe functional
decline. Although there has been a decline in the incidence of HIV-D as presenting
manifestation of AIDS, the overall prevalence of the HIV-related NCI might be increasing.
In HIV-infected patients the lifetime prevalence of HIV-D is 5 to 10%, and the prevalence
of MND is around 20% in patients with advanced diseases. Among general population
HIV-D is the most common cause of dementia in persons age 25-40 years.
Epidemiological studies indicate a change in risk factors for HIV-D. The CD4 cell count at
diagnosis of HIV-D, being 50 to 100 in the pre-HAART era, has now significantly
increased. New risk factors for HIV-related NCI have been identified: duration of HIV
infection, HCV co-infection, lower nadir CD4 count. Moreover, as patients are living
longer, they are now more exposed to other factors that could affect cognition like
testosterone deficiency, aging, and increased cholesterol and triglyceride levels. HIV-D is
a debilitating disorder, that negatively affects patient's ability to perform activities of daily
living, quality of life, adherence to antiretroviral therapy, and survival. Before the
introduction of HAART, HIV-associated NCI was recognized as an independent risk factor
for death. We have recently shown that the HIV-associated NCI is associated with a
significantly greater mortality even in patients receiving HAART and that, after adjustment
for confounding variables, the increased risk of death for neurocognitively impaired
patients persists only among patients with virological failure, while the survival probability
of patients with durable virological suppression is not affected by NCI. The optimal
treatment for HIV-D has not been established, but there are strong evidences HAART is
effective in treating the cognitive impairment. In patients with HIV-D the primary goal of
antiretroviral treatment is to achieve complete virological suppression both in plasma and
in the CSF. It remains controversial whether a combination drugs with good CSF
penetration is essential for an effective treatment of HIV-D. Although HAART can reverse
HIV-D, a substantial proportion patients may continue to show a persistent NCI despite
HAART. We have assess prevalence and predictors of persistent NCI despite long-term
HAART. Our data indicate, that although HAART is associated with an improvement in
cognitive abnormalities, the impairment may persist in more than fifty percent of patients
despite more than 5 years of HAART. Positive HCV serology, lower education and
greater impairment in measures exploring memory and concentration is associated with
persistent NCI. At multivariable analysis the severity of neurocognitive impairment
appears to be the strongest predictor of persistent NCI despite HAART. Our data indicate
that HAART should be initiated as soon as NCI is diagnosed to avoid a potentially
irreversible neurological damage. Additional treatment strategies are needed in patients
with persistent NCI despite HAART.
ABSTRACTS
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