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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
Disease Progression in HIV-1-Infected Viremic Controllers
Katherine C Groves1, David F Bibby, Duncan A Clark
1Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary University of London.
Journal of Acquired Immune Deficiency Syndromes (1999)
|August 21, 2012
Summary
In HIV-1 infection, "discord controllers" with low viral RNA but low CD4 T-cells show high viral DNA. This suggests HIV-1 DNA load, not RNA, may better predict disease progression.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- The mechanism of CD4 T-cell decline in HIV-1 infection is not fully understood, though viral replication is implicated.
- Viremic controllers typically maintain high CD4 T-cell counts despite detectable viral RNA.
- A subgroup of "discord controllers" with low CD4 T-cells despite low viral RNA presents clinical uncertainty.
Purpose of the Study:
- To investigate the viral and host immune dynamics in discord controllers.
- To compare cellular HIV-1 DNA load, T-cell populations, and activation markers between discord controllers, typical controllers, and progressors.
Main Methods:
- Compared discord controllers (viral RNA <2000 copies/mL, CD4 <450 cells/mm³) with typical controllers (viral RNA <2000 copies/mL, CD4 >450 cells/mm³) and progressors (viral RNA >10,000 copies/mL, CD4 <450 cells/mm³).
- Quantified CD4/CD8 naive/central memory/effector memory subsets and activation markers (CD38HLA-DR).
- Measured cellular HIV-1 DNA load.
Main Results:
- Discord controllers exhibited high HIV-1 DNA load and naive CD4 T-cell depletion, similar to progressors.
- Discord controllers showed higher CD4 T-cell activation across subsets compared to typical controllers.
- CD8 T-cell activation was lower in discord controllers and typical controllers compared to progressors.
Conclusions:
- CD4 T-cell activation is linked to HIV-1 disease progression.
- HIV-1 DNA load may be a more accurate marker of viral replication and disease progression than viral RNA load.
- Lower CD8 T-cell activation correlates with low viral RNA but not disease progression or viral DNA load.
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