Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment. 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., & CHARTER Study Group Virology, 433(2):498–505, November, 2012.
doi  abstract   bibtex   
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.
@article{hightower_higher_2012,
	title = {Higher {HIV}-1 genetic diversity is associated with {AIDS} and neuropsychological impairment},
	volume = {433},
	issn = {1096-0341},
	doi = {10.1016/j.virol.2012.08.028},
	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.},
	language = {eng},
	number = {2},
	journal = {Virology},
	author = {Hightower, George K. and Wong, Joseph K. and Letendre, Scott L. and Umlauf, Anya A. and Ellis, Ronald J. and Ignacio, Caroline C. and Heaton, Robert K. and Collier, Ann C. and Marra, Christina M. and Clifford, David B. and Gelman, Benjamin B. and McArthur, Justin C. and Morgello, Susan and Simpson, David M. and McCutchan, J. A. and Grant, Igor and Little, Susan J. and Richman, Douglas D. and Kosakovsky Pond, Sergei L. and Smith, Davey M. and {CHARTER Study Group}},
	month = nov,
	year = {2012},
	pmid = {22999095},
	pmcid = {PMC3466337},
	keywords = {Acquired Immunodeficiency Syndrome, Adult, Cohort Studies, Female, Genes, pol, Genetic Variation, HIV Infections, HIV-1, Humans, Male, Middle Aged, Neuropsychological Tests, RNA, Viral},
	pages = {498--505}
}

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