Abstract

E-mail Abstract Author Add To Itinerary Session Search Abstracts Program

Session 71 Poster Session IL-2 and Other Forms of Immunotherapy Session Time: 4:30-6:30 pm Room 4E-F

526-M. Activation of an HIV-1 Reservoir during Hematopoietic Progenitor Cell Mobilization R. Rapaport*, D. Kuritzkes, R. T. Schooley, and T. B. Campbell Univ. of Colorado Hlth. Sci. Ctr., Denver Background: Although latently infected resting CD4+ T cells serve as a reservoir for HIV-1, other undefined viral reservoirs may also exist and contribute to viral persistence. This study investigated the possibility that increased viral replication during G-CSF-mediated hematopoietic stem cell (HSC) mobilization resulted from activation of a unique HIV-1 reservoir. Methods: Subjects (n=3) who experienced a > 1.0 log10 increase in plasma HIV-1 RNA during HSC mobilization by G-CSF during ACTG 285 were studied. For each subject the env C2-V3 region was amplified by RT-PCR of plasma specimens collected at study entry and peak viremia during HSC mobilization. The C2-V3 nucleotide sequence of 10 molecular clones from each time point was determined. Genetic relationships of C2-V3 sequences were inferred by neighbor-joining methods (DNADIST, NEIGHBOR and SEQBOOT in PHYLIP 3.5). Results: All C2-V3 sequences from each subject grouped in phyletic clusters distinct from clusters formed by sequences from other subjects and from commonlaboratory strains. For all 3 subjects, 50-70% of the clones generated from plasma collected during HSC mobilization grouped into unique intrasubject subclusters. The unique intrasubject subclusters accounted for 53-71% of the peak increase in plasma HIV-1 RNA observed during HSC mobilization. For the 2 subjects on antiretroviral therapy during HSC mobilization the the unique post-mobilization subcluster and the baseline quasispecies were distantly related and predicted to share a most recent common ancestor. In contrast, the unique post-mobilization subcluster from the subject who did not receive antiretroviral therapy was closely related to the pre-mobilization plasma quasispecies. Conclusions: HSC mobilization with G-CSF caused a rapid change in the plasma quasispecies. This change was associated with the appearance of a new majority virus not detected at baseline. Our findings suggest that most of the increase in plasma HIV-1 RNA observed during HSC mobilization reflected production of HIV-1 by a pool of infected cells different from those that contributed to the plasma quasispecies at baseline.

©2002 9th Conference on Retroviruses and Opportunistic Infections