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Updated: Jul 26, 2026
11:10
Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
Published on: December 27, 2010
Causal pathways for CCR5 genotype and HIV progression.
1Department of Biostatistics, University of Michigan, Ann Arbor 48109-0848, USA.
Journal of Acquired Immune Deficiency Syndromes (1999)
|March 29, 2000
Summary
CCR5 heterozygosity offers protection against HIV-1 progression by preserving CD4+ T-cell counts and delaying AIDS development. This protective effect is mediated through CD4+ T-cell levels, not initial viral load.
Area of Science:
- Immunogenetics
- Virology
- Epidemiology
Background:
- The CCR5 receptor is crucial for HIV-1 entry into host cells.
- A 32-base pair deletion in the CCR5 gene confers HIV-1 resistance.
- CCR5 heterozygosity is linked to delayed disease progression in HIV-1-infected individuals.
Purpose of the Study:
- To investigate the impact of CCR5 heterozygosity on HIV-1 disease progression.
- To determine if CCR5 heterozygosity affects CD4+ T-cell counts and clinical AIDS.
- To elucidate whether the effect of CCR5 heterozygosity on AIDS is direct or mediated by CD4+ T-cell counts.
Main Methods:
- Utilized a unified statistical model to analyze CD4+ T-cell count decline and AIDS occurrence.
- Employed data from the Multicenter AIDS Cohort Study.
- Assessed the mediating role of CD4+ T-cell counts and adjusted for initial viral load.
Main Results:
- CCR5 heterozygosity demonstrated a protective effect on both CD4+ T-cell count progression and AIDS occurrence.
- The protective effect against AIDS was found to be entirely mediated by CD4+ T-cell counts.
- CCR5 heterozygosity did not predict CD4+ T-cell progression or AIDS development beyond its association with early viral load.
Conclusions:
- CCR5 heterozygosity plays a significant protective role in HIV-1 disease progression.
- The mechanism of protection involves maintaining higher CD4+ T-cell counts.
- Early viral load is a key factor, and CCR5 heterozygosity's impact is largely explained by its effect on viral load and subsequent CD4+ T-cell levels.
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