1. Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment
- Author
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Hightower, George K, Wong, Joseph K, Letendre, Scott L, Umlauf, Anya A, Ellis, Ronald J, Ignacio, Caroline C, Heaton, Robert K, Collier, Ann C, Marra, Christina M, Clifford, David B, Gelman, Benjamin B, McArthur, Justin C, Morgello, Susan, Simpson, David M, McCutchan, JA, Grant, Igor, Little, Susan J, Richman, Douglas D, Pond, Sergei L Kosakovsky, Smith, Davey M, and Group, the CHARTER Study
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Mental Health ,Acquired Immunodeficiency Syndrome ,Adult ,Cohort Studies ,Female ,Genes ,pol ,Genetic Variation ,HIV Infections ,HIV-1 ,Humans ,Male ,Middle Aged ,Neuropsychological Tests ,RNA ,Viral ,HIV ,AIDS ,Genetic diversity ,Neuropsychological impairment ,Viral population dynamics ,CHARTER Study Group ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Agricultural ,veterinary and food sciences ,Biological sciences ,Biomedical and clinical sciences - 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.
- Published
- 2012