Publication Abstract Display
Type: Published Manuscript
Title: Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment.
Authors: Hightower GK, Wong JK, Letendre SL, Umlauf AA, Ellis RJ, Ignacio CC, Heaton RK, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Grant I, Little SJ, Richman DD, Pond SLK, Smith DM, and the CHARTER Study Group
Year: 2012
Publication: Virology
Volume: 433 Issue: 2 Pages: 498-505
Abstract:Standard methods used to estimate HIV-1 population diversity are often resource intensive (e.g., single genome amplification, clonal amplification and pyrosequencing) and not well suited for large study cohorts. Additional approaches are needed to address the relationships between intraindividual HIV-1 genetic diversity and 2 disease. With a small cohort of individuals, we validated three methods for measuring diversity: Shannon entropy and average pairwise distance (APD) using single genome sequences, and counts of mixed bases (i.e. ambiguous nucleotides) from population based sequences. In a large cohort, we then used the mixed base approach to determine associations between measure HIV-1 diversity and HIV associated disease. Normalized counts of mixed bases correlated with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who underwent neuropsychological and clinical assessments (n=187), increased HIV-1 population diversity was associated with both a diagnosis of AIDS and neuropsychological impairment.

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