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P16-28. The first year: early correlates of long-term HIV progression
Retrovirology volume 6, Article number: P257 (2009)
SIV studies reveal dramatic, systemic destruction of CD4+ T-cells in acute disease; this, and early levels of central memory (TCM) subsets predict progression to death independently of viral load. Similar data are not available for HIV, because samples from early disease are rare and long, untreated follow-up is usually not possible. We analyzed a large cohort of confirmed seroconverters to test whether T-cell and viral dynamics in early disease predict long-term progression.
Samples from 466 untreated, early infection individuals (median = 225 days), with substantial follow-up (median = 4 years), were studied using two 13-color flow cytometry panels, including: A) CD45RO, CD27, CD28, CCR5, CCR7, CD127, CD57, and Ki-67 (unstimulated) and B) IFNγ, IL2, TNFα, CD154, CD107a, CD45RO, CD27, CCR7, and CD57 (after stimulation with HIV antigens). We also measured cell-associated viral load (CAVL) in various CD4+ T-cell subsets. We correlated T-cell subset representation, CAVL, and the magnitude, quality, and phenotype of HIV-specific T cells with disease progression.
TCM levels at the earliest HIV+ visit did not predict long-term outcome. However, the following were associated with slow progression: high levels of long-lived cells (naive or CD127+ memory CD8), low Ki-67 expression, and low CAVL during the first 7.5 months. Notably, CAVL was present in naive cells. Also, no single T-cell function (e.g. IFNγ) had predictive value; however, rapid progressors (AIDS < 4.6 years) had "higher" levels of polyfunctional CD4+ T-cells in early disease than AIDS-free subjects. Finally, cytokine responses to Gag and Env differed dramatically.
These results suggest: 1) early depletion of precursor cells, mediated by proliferation/differentiation, is a poor prognostic factor independent of antigen load, 2) Ki-67 measurements can inform early treatment decisions, and 3) the quality of the T-cell response to HIV early in disease impacts long-term progression. These data inform experimental design in vaccine trials that test efficacy after breakthrough infections.
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Chattopadhyay, P., Brodie, T., Ganesan, A. et al. P16-28. The first year: early correlates of long-term HIV progression. Retrovirology 6, P257 (2009). https://doi.org/10.1186/1742-4690-6-S3-P257
- Viral Load
- Breakthrough Infection
- Naive Cell
- Early Depletion
- Systemic Destruction