HIV-associated Neurocognitive Impairment Remains Prevalent in the Era of Combination ART: The CHARTER Study
R Heaton1, D Franklin1, D Clifford2, S Woods1, M Rivera Mindt3,4, O Vigil1, M Taylor1, T Marcotte1, H Atkinson1, and Igor Grant*1
1Univ of California, San Diego, US; 2Washington Univ, St Louis, MO, US; 3Mt Sinai Sch of Med, New York, NY, US; and 4Fordham Univ, New York, NY, US
Background: Combination ART (cART) typically
suppresses HIV viral replication in plasma and cerebrospinal fluid (CSF), but
its long-term effects on neurocognitive impairment (NCI) are unclear. This
multi-site study examined the prevalence and predictors of NCI in the cART era,
within an HIV+ sample. We hypothesized that cART would be associated
with a lower prevalence of NCI.
Methods: We gave comprehensive neuromedical and
neuropsychological evaluations to 1555 HIV+ patients at 6 university
clinics across the United States (age 43.2±8.6; education 12.7±2.5 years; 77%
male; ethnicity = 49% African American; 9% Hispanic; 39% non-Hispanic white; 3%
other; 28% intravenous drug users; 58% men who have sex with men) received.
Participants were unselected in that there were no neuromedical or psychiatric
exclusions. Participants were classified according to severity of their co-morbidity
(factors that might contribute to NCI independent of HIV, e.g., epilepsy): minimal,
n = 843; moderate, n = 473; and severe, n = 240.
Results: Overall, 45% of the cohort had NCI based on
a global rating ≥5 derived from comprehensive neuropsychological testing,
with rates increased in groups with greater co-morbidity (39% vs 54% vs 79%,
respectively; p <0.01). NCI prevalence was higher with AIDS diagnosis
and low nadir CD4 only in the minimal co-morbidity group. In this group, a
higher rate of NCI was found in those currently on cART (43% vs 31%, p <0.01),
probably because 74% of AIDS vs 27% of non-AIDS (p <0.01) were on cART.
In contrast, the rates of NCI in the moderate or severe co-morbidity groups
were 64% on cART and 58% off cART (p=.13). For treated patients in the minimal
co-morbidity group with no history of severe immunosuppression (nadir CD4 >200;
n = 184), those with HIV suppression on treatment had lower NCI rates (29% vs
45% for those with detectable plasma viral load, p = 0.02).
Conclusions: A high prevalence of NCI was found in
this large geographically and demographically diverse HIV+
population despite the majority receiving cART. Substantial impairment was seen
even among participants without significant co-morbidity. Biological and
clinical indicators of HIV disease severity were related to NCI only in
patients without significant co-morbidities. Thus, both HIV and co-morbidity
contribute to NCI in the cART era. The results also indicate the importance of
clinical studies to determine whether cART-related HIV suppression may protect
the central nervous system more effectively if started earlier in the course of