Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment

George K. Hightower, Joseph K. Wong, Scott L. Letendre, Anya A. Umlauf, Ronald J. Ellis, Caroline C. Ignacio, Robert K. Heaton, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin B. Gelman, Justin C. McArthur, Susan Morgello, David M. Simpson, J. A. McCutchan, Igor Grant, Susan J. Little, Douglas D. Richman, Sergei L. Kosakovsky Pond, Davey M. Smith

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)498-505
Number of pages8
JournalVirology
Volume433
Issue number2
DOIs
StatePublished - Nov 25 2012

Keywords

  • AIDS
  • Genetic diversity
  • HIV
  • Neuropsychological impairment
  • Viral population dynamics

ASJC Scopus subject areas

  • Virology

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    Hightower, G. K., Wong, J. K., Letendre, S. L., Umlauf, A. A., Ellis, R. J., Ignacio, C. C., Heaton, R. K., Collier, A. C., Marra, C. M., Clifford, D. B., Gelman, B. B., McArthur, J. C., Morgello, S., Simpson, D. M., McCutchan, J. A., Grant, I., Little, S. J., Richman, D. D., Kosakovsky Pond, S. L., & Smith, D. M. (2012). Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment. Virology, 433(2), 498-505. https://doi.org/10.1016/j.virol.2012.08.028