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Abstract
PERSISTENCE OF LOW-GRADE HIV-1 REPLICATION IN RESTING MEMORY T CELLS IN PERSONS INITIATING EARLY AND AGGRESIVE ANTIRETROVIRAL THERAPY
BRODIE S, BERREY M, PATTERSON B, MULLINS J, STEVENSON M, COREY L
BACKGROUND: Early combination antiretroviral therapy may preserve HIV-1-suppressive mechanisms important in the containment of viral replication following the interruption of therapy.
METHODS: We use well-standardized assays with single molecule sensitivity and methods for isolating extremely pure populations of activated and resting (nonactivated and nondividing) memory (CD45RO+/CD62L-) CD4+ T cells in patients undergoing combination antiretroviral therapy first administered during the acute retroviral syndrome.
RESULTS: Combination antiretroviral therapy when administered during the acute retroviral syndrome rapidly lowered plasma HIV-1 RNA to levels undetectable (<50 copies/ml, weeks 9 to 15, 95% CI) and significantly reduced the number of metabolically-active CD4+ T cells expressing HIV-1 RNA ?4-fold and the mean viral copy number within these cells >2 log10 (week 16, 95% CI). Still, a small population of memory CD4+ T cells (CD45RO+/CD62L-) with a quiescent phenotype (nonactivated [HLA-DR-, CD25-/38-/69-] and nonproliferating [G0]) produced viral transcripts at relatively unchanged levels during a 12 month course of therapy. These quiescent T cells also demonstrated tat fusion transcripts, 2-LTR circles, produced infectious virus, and showed time-ordered evolution of viral env sequence throughout therapy. Thus, potent antiretroviral therapy, when administered during acute infection, markedly reduced cell-associated HIV-1 gene expression, but did not fully inhibit virus replication, having its least effect on a small but remarkably uniform population of nonactivated and nondividing memory T cells.
CONCLUSIONS: The extraordinary stability of this reservoir may imply escape from immune surveillence by mechanisms other than viral mutation and gradual reseeding of the cellular pool by a very low level of ongoing viral replication. These findings have important implications for the clinical management of HIV-1-infected individuals and eradication strategies.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
24
Suggested Citation
"BRODIES, et al.
PERSISTENCE OF LOW-GRADE HIV-1 REPLICATION IN RESTING MEMORY T CELLS IN PERSONS INITIATING EARLY AND AGGRESIVE ANTIRETROVIRAL THERAPY.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
24"
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