Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment.
Title | Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Hightower, GK, Wong, JK, Letendre, SL, Umlauf, AA, Ellis, RJ, Ignacio, CC, Heaton, RK, Collier, AC, Marra, CM, Clifford, DB, Gelman, BB, McArthur, JC, Morgello, S, Simpson, DM, McCutchan, JA, Grant, I, Little, SJ, Richman, DD, Pond, SLKosakovs, Smith, DM |
Corporate Authors | CHARTER Study Group |
Journal | Virology |
Volume | 433 |
Issue | 2 |
Pagination | 498-505 |
Date Published | 2012 Nov 25 |
ISSN | 1096-0341 |
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 | 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. |
DOI | 10.1016/j.virol.2012.08.028 |
Alternate Journal | Virology |
PubMed ID | 22999095 |
PubMed Central ID | PMC3466337 |
Grant List | K24 AI100665 / AI / NIAID NIH HHS / United States R01 AI057167 / AI / NIAID NIH HHS / United States NS51132 / NS / NINDS NIH HHS / United States R21 AI077304 / AI / NIAID NIH HHS / United States R01 NS051132 / NS / NINDS NIH HHS / United States R01 AI047745 / AI / NIAID NIH HHS / United States K24 AI064086 / AI / NIAID NIH HHS / United States UM1 AI069432 / AI / NIAID NIH HHS / United States AI047745 / AI / NIAID NIH HHS / United States AI38858 / AI / NIAID NIH HHS / United States R01 AI043752 / AI / NIAID NIH HHS / United States AI36214 / AI / NIAID NIH HHS / United States U01 AI027670 / AI / NIAID NIH HHS / United States MH083552 / MH / NIMH NIH HHS / United States R21 AI047745 / AI / NIAID NIH HHS / United States DA12065 / DA / NIDA NIH HHS / United States AI29164 / AI / NIAID NIH HHS / United States R37 AI029164 / AI / NIAID NIH HHS / United States U01 AI069432 / AI / NIAID NIH HHS / United States AI27670 / AI / NIAID NIH HHS / United States U01 AI038858 / AI / NIAID NIH HHS / United States U01 AI043638 / AI / NIAID NIH HHS / United States DP1 DA034978 / DA / NIDA NIH HHS / United States R56 AI047745 / AI / NIAID NIH HHS / United States P30 AI027763 / AI / NIAID NIH HHS / United States DA034978 / DA / NIDA NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States R21 AI080353 / AI / NIAID NIH HHS / United States P01 DA012065 / DA / NIDA NIH HHS / United States AI64086 / AI / NIAID NIH HHS / United States MH62512 / MH / NIMH NIH HHS / United States P30 AI036214 / AI / NIAID NIH HHS / United States UL1 RR029887 / RR / NCRR NIH HHS / United States R01 MH083552 / MH / NIMH NIH HHS / United States AI57167 / AI / NIAID NIH HHS / United States R01 MH097520 / MH / NIMH NIH HHS / United States AI43638 / AI / NIAID NIH HHS / United States AI43752 / AI / NIAID NIH HHS / United States AI077304 / AI / NIAID NIH HHS / United States U19 AI090970 / AI / NIAID NIH HHS / United States AI47745 / AI / NIAID NIH HHS / United States AI69432 / AI / NIAID NIH HHS / United States R24 AI106039 / AI / NIAID NIH HHS / United States |