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

Type: Published Abstract
Title: Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment.
Authors: Hightower G, Wong J, Letendre S, Umlauf A, Ellis R, Ignacio C, Heaton R, Grant I, Richman D, Smith D, and the CHARTER Group
Year: 2011
Publication: 18th Conference on Retroviruses and Opportunistic Infections, Boston, Mass
Volume: Issue: Pages:
Abstract:Background: There are conflicting reports as to whether or not genetic diversity in the HIV population is associated with disease progression. Previous studies have used relatively small cohorts because conventional methods of measuring viral diversity are often expensive and laborious. We validated a novel method of measuring viral diversity using mixed bases in population-based sequences and then investigated the relationship between genetic diversity and HIV disease state and neuropsychological functioning in a relatively large (n=177) well-characterized cohort. Methods: Participants enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) received neuromedical, neuropschological, and laboratory examinations. HIV RNA was extracted from collected paired blood and CSF samples, pol sequenced and manually edited (Viroseq v2.6). Viral population diversity was estimated by calculating the number of mixed bases over the length of the sequence, i.e. Total Mixed Base Index, using HyPhy (Kosakovsky Pond 2005). Multivariable analysis included CD4 count, antiretroviral (ARV) use, resistance associated mutations (RAMs), AIDS, duration of infection, blood and CSF viral load, and blood and CSF Total Mixed Base Index. Results: Participants were mostly White men in their mid-30s and 34% were receiving ARV at sampling. Median blood and CSF HIV RNA levels were 4.6 and 3.6 log10 copies/ml, and current and nadir CD4 count of 365 and 253 cells/ul. In multivariable logistic regression analysis, Total Mixed Base Index in blood and CSF were independently and positively associated with AIDS (blood p=0.009, CSF p=0.02) and neuropsychological impairment (blood p=0.02, CSF p=0.03). The RAMs M184V and K103N were detected in 4% and 8% of participants and were not associated with neuropsychological impairment. Conclusions: Using a novel method for estimating diversity, we provide evidence that HIV-1 population diversity is positively associated with disease progression, specifically AIDS and neuropsychological impairment. The presence of M184V and K103N were not associated with neuropsychological performance; however, this analysis was limited by the low prevalence of RAMs.