Session 59Poster Presentations Viral Genetic Diversity Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall A
495 Early HIV-1 Viral Diversity Associated with Rapid Disease Progression Geoffrey S. Gottlieb*1, Mark A. Jensen1, David C. Nickle1, Kim G. Wong1, Fusheng Li1, Gerald H. Learn1, Joseph B. Margolick2, James I. Mullins1 1Univ of Washington, Seattle and 2Johns Hopkins Bloomberg Sch of Publ Hlth, Baltimore, MD
Background: The high levels of global and intra-patient viral diversity observed in HIV infection are a direct consequence of the rapid turnover and high mutation rates intrinsic to the virus, as well as selective forces encountered within the host. How this extensive viral diversity impacts HIV disease progression is unclear. Here we considered the possibility that either primary infection with, or early establishment of, a highly diverse virus population may enable the virus to more rapidly adapt to and exploit available cellular niches leading to more rapid disease progression.
Methods: We used phylogenetic methods to analyze intra-patient HIV-1 viral diversity present within the first year of infection by PCR, cloning, and sequencing of C2-V5 envelope region virus populations within 29 subjects from the Multicenter AIDS Cohort Study (MACS). We compared levels of this early viral diversity with rates of disease progression; time to clinical AIDS, time to CD4 < 200/ul, as well as set point plasma viral load.
Results: We found an inverse correlation between early viral diversity and time to clinical AIDS (R2 = 0.17, p = 0.027). In addition, there was an inverse trend between early viral diversity and time to CD4 < 200/ul (R2 = 0.11, p = 0.083) as well as a positive trend between early viral diversity and set point plasma viral load (R2 = 0.12, p = 0.066)
Conclusions: There appears to be an association between levels of HIV viral diversity early in infection and the rate subsequent disease progression. This association may result, in part, due to an increase in plasma viral load that appears to be associated with increasing viral diversity. Larger studies to further evaluate this association are needed.
