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

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

来源：Virology, 2012, 433(2): 498-505.

DOI：10.1016/j.virol.2012.08.028

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

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. Published by Elsevier Inc.

• 出版日期2012-11-25