HIV-associated neurocognitive disorder (HAND) in acute and early HIV infection.

Type: Poster
Title: HIV-associated neurocognitive disorder (HAND) in acute and early HIV infection.
Authors: Moore DJ, Letendre SL, Deutsch R, Little S, Smith D, Franklin DR, Rosario D, Heaton RK, Grant I, for the CHARTER Group
Date: 02-16-2010
Abstract:Background: HIV-associated neurocognitive disorder (HAND) persists despite potent antiretroviral therapy (ART). Most research focuses on chronic HIV infection (CH) but events during acute and early HIV infection (AEH) may set the stage for development and persistence of HAND. Methods: To determine prevalence of HAND in AEH, we examined 77 participants (pts) within <1 year of estimated date of infection (mean duration 20 weeks), with comprehensive neuropsychological (NP) testing and compared them to 52 HIV seronegative pts (HIV-) of similar background. To assess potential mechanisms of HAND in AEH, we compared biomarker levels in AEH pts to those in 83 pts with CH, defined as ≥ 1 year of infection (mean 7.0 years) selected to be similar on comorbidity factors. The majority of AEH pts were ART naïve (77%) as compared to 33% of CH pts. We calculated a global NP deficit score (GDS), and determined NP impairment from this score. We evaluated mean comparisons with ANOVAs and calculated Cohen’s d effect sizes. Using linear regression, we examined possible predictors of NP functioning: stage of infection, plasma viral load, peak plasma viral load, CD4 count, nadir CD4 count, a panel of 11 serum biomarkers, current ART status, and HCV coinfection. Results: AEH pts had an NP impairment rate of 26% as compared to 29% of CH and 13% of HIV- participants (p=0.02). There was a medium effect between HIV- and AEH (d=.40), a slightly larger effect between HIV- and CH (d=.52), and a minimal effect between AEH and CH (d=.14). There were trends toward elevated levels of MCP-1 (p=.07) and IP-10 (p=.09) in AEH as compared to CH. In univariable analyses of all pts, worse NP functioning (p<.10) was associated with higher plasma viral load, lower nadir CD4+ cell counts, AIDS diagnosis, current ART use, and higher IL-6 levels (all p’s <.10). Using all pts, a model examining main effects and interactions of candidate predictors revealed that ART use (p=.02) and higher levels of IL-6 (p=.03) were associated with worse NP functioning (R2=.08, p=.005). Disease stage (AEH vs. CH) was not. Conclusions: Even in the earliest stages of HIV infection, NP impairment rates are double those in HIV- persons. Regardless of chronicity, those who were on ART (associated with worse HIV disease) and those with elevated serum levels of IL-6 were more likely to have worse NP performance. Because most of the AEH pts were untreated, it remains to be determined if earlier ART may lessen the burden of HAND