Valerio Tozzi with the Italian
National Institute of Infectious Disease and colleagues looked at prevalence of
and risk factors for HIV-associated neurocognitive disorders, or HAND, from
the advent of combination antiretroviral therapy (ART) in 1996 through 2010.
They also assessed severity and qualitative changes in cognitive function.
This observational study included 1375 HIV-positive
patients on antiretroviral therapy at a single site in Italy. About 75% were
men, the median age was 42 years, and they had a median 13 years of education.
People with psychiatric or neurological conditions and active drug users were
Participants had been infected with HIV for a median
of six years and about one-third had an AIDS diagnosis. The current median CD4
cell count was near 400 cells/mm3, but the nadir or lowest-ever
count was 165 cells/mm3.
Participants underwent a series of about a dozen
neuropsychological tests to measured cognitive function in five domains. These
tests measured abilities such as verbal learning and ability to draw a complex
figure from memory. Performance was compared to normal values for the HIV
negative general population matched for sex and age.
The researchers used statistical methods to determine
factors associated with higher or lower risk of HAND, looking at three clinical categories of cognitive impairment:
HIV-associated dementia, mild neurocognitive disorder, and asymptomatic neurocognitive
Overall, HAND prevalence decreased only slightly over
the course of the study, falling from 46% during 1996-1998 to 38% during
2008-2010. Severity also shifted over time. During 1996-1998, 30% of
participants had dementia or mild neurocognitive impairment. Over time this fell
steadily, to 18% by 2008-2010, but the proportion of people with asymptomatic
In an unadjusted analysis, people with HAND were
significantly older on average, older when they had their first HIV test, and
had been infected for a longer duration than those without; they also had about
two years less education. . People with HAND were much more likely to have
received an AIDS diagnosis than those without (49% vs 24%). They had lower
current (349 vs 478 cells/mm3) and nadir (158 vs 231 cells/mm3)
CD4 counts and were more likely to have hepatitis C co-infection (51% vs 31%).
In a multivariate analysis that controlled for others
factors, five factors remained "strongly and significantly"
associated with HAND: older age, higher education level, AIDS diagnosis, and
current CD4 cell count.
Nadir CD4 count and hepatitis C status were no longer
significant predictors of HAND, conflicting with some other studies. Tozzi
explained that the strong association with AIDS diagnosis indicated that history
of immune deficiency had an influence, but suggested that persistent rather that past immunodeficiency is most
Looking only at 569 people with
dementia or mild symptomatic impairment, age, education, AIDS diagnosis, and
current CD4 count were again significant predictors in a multivariate analysis.
But here, having cardiovascular risk factors was also associated with a higher
likelihood of HAND. Tozzi suggested this link might be related to chronic
Impairment in specific domains was
variable. The researchers noted some evidence of reduced impairment in measures of visual memory and spatial perception, but most areas¾including attention and memory, motor skills, and processing speed¾remained about the same, indicating "very limited
evidence" for a change in HAND neurocognitive profile.