Publication Abstract Display
Type: Published Manuscript
Title: Dual-mixed HIV-1 co-receptor tropism is associated with HIV associated neurocognitive dysfunction.
Authors: Morris S, Woods SP, Deutsch R, Little SJ, Wagner G, Morgan EE, Heaton RK, Letendre SL, Grant I, Smith DM and the TMARC Group
Year: 2013
Publication: Journal of NeuroVirology
Volume: 19 Issue: 5 Pages: 488-494
Abstract:Background HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not been described. Methods This study assembled data on 72 recently HIV-infected men who had undergone up to 4 sequential comprehensive neurocognitive assessments over a median of 160 days (IQR 138-192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model regression was used to determine the association between HAND and viral tropism (X4, R5 or dual-mixed (DM)) adjusting for estimated date of infection (EDI), plasma viral load, CD4 count and methamphetamine use. Results Five subjects (6.9%, 95% CI 3, 15.2) had dual mixed tropism (DM) at their earliest available blood sample. One additional subjectís viral population converted to DM occurred before the first neurocognitive assessment and four converted to DM in subsequent sampling at a median EDI of 10.1 months (IQR 7.2-12.2). There were 44 (61.1%) subjects that demonstrated HAND on at least one study visit. Mixed effect multivariable logistic regression determined that HAND was associated with DM tropism (odds ratio 4.4, 95% CI 0.9, 20.5) and shorter EDI (odds ratio 1.1 per month earlier, 95% CI 1.0-1.2). Conclusion This study found that recent HIV-1 infection and the development of DM tropism were associated with HAND. The importance of viral factors in HAND reaffirms the need for early antiretroviral treatment to prevent tropism switching.

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