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Publication Abstract Display
Type: Poster
Title: HIV-Associated neurocognitive disorders are correlated with X4/dual mixed tropism.
Authors: Morris S, Little S, Woods SP, Grant I, Smith DM, and the TMARC Study Group
Date: 03-05-2012
Abstract:Background: To determine if HIV-associated neurocognitive disorders (HAND) is correlated with CXCR4 or dual mixed HIV tropism (X4/DM), we investigated the emergence of X4/DM virus following primary HIV infection and its association with HAND. Methods: Persons with acute or early HIV infection (estimated duration of infection [EDI] within previous 6 months) were enrolled in an observational study to assess neurocognitive status, methamphetamine use, viral load, CD4 counts, and HIV co-receptor tropism (Trofile ES, Monogram) over 24 weeks. If Trofile assays were unreportable (e.g., low viral load), viral tropism was predicted using bulk sequences of the V3 loop. Univariate and multivariate analyses using a general estimating equation (GEE) model (SAS v9) were performed to determine the association of HIV tropism, demographics, EDI, viral load (log10copies/mL), CD4 (cells/mL), and methamphetamine use with neurocognitive measures. Results: Seventy-two subjects were enrolled with a median EDI of 70 days (IQR 25 to 86) and the baseline neurocognitive assessment was performed at a median EDI of 82.5 days (IQR 31 to 123). During follow up, the mean nadir CD4 was 503 cells/mL, and the mean peak viral load was 4.9 log10copies/mL. On study, methamphetamine use was reported by 20% of participants. Four of 72 (5.5%) subjects had X4/DM tropic virus at baseline, and 5 other subjects had X4/DM identified at a later time point (total 9/72 = 12.5%). HAND was detected in 49% of participants at baseline and 47% of participants during at least one follow-up visit (maximum of 2 additional evaluations). HAND was found in 78% of individuals who harbored X4/DM tropic virus compared to 59% with R5 only. The presence of X4/DM tropism was the only factor independently associated with HAND (adjusted odds ratio of 4.40 [95%CI 1.00 to 19.23]) in a multivariate GEE model that included repeated measures of tropism, EDI, CD4, viral load, and methamphetamine use. Conclusions: This study found that a large proportion of individuals with recent HIV infection have neurocognitive impairment. X4/DM viral tropism occurs in the earliest stages of HIV infection and is a unique predictor of HAND. Possible biological reasons for this finding could be systemic immune activation or direct collateral effects of virus on CXCR4 receptors in brain tissues.

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