Date Published:
2012 Nov 25

Publication Type:
Journal Article

Authors:

G.K. Hightower
J.K. Wong
S.L. Letendre
A.A. Umlauf
R.J. Ellis
C.C. Ignacio
R.K. Heaton
A.C. Collier
C.M. Marra
D.B. Clifford
B.B. Gelman
J.C. McArthur
S. Morgello
D.M. Simpson
J.A. McCutchan
I. Grant
S.J. Little
D.D. Richman
S.L.Kosakovs Pond
D.M. Smith

Secondary:
Virology

Volume:
433

Pagination:
498-505

Issue:
2

PMID:
22999095

URL:
https://pubmed.ncbi.nlm.nih.gov/22999095

DOI:
10.1016/j.virol.2012.08.028

Keywords:
Acquired Immunodeficiency Syndrome;Adult;CHARTER;Cohort Studies;Female;Genes, pol;Genetic Variation;HIV Infections;HIV-1;Humans;Internal;Male;Middle Aged;Neuropsychological Tests;RNA, Viral

Abstract:
<p>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.</p>