title: Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment.
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.
authors.affiliation: University of California San Diego, La Jolla, CA 92093-0679, USA.
authors.forename: George K
authors.initials: GK
authors.lastname: Hightower
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Anya A
authors.initials: AA
authors.lastname: Umlauf
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Ignacio
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: J A
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Little
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kosakovsky Pond
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000523:psychology* / Q000821:virology*; D000328:Adult; D015331:Cohort Studies; D005260:Female; D015751:Genes, pol; D014644:Genetic Variation; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000523:psychology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D012367:RNA, Viral