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Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection
M L Romiti1, C Colognesi, C Cancrini
1Division of Immunology and Infectious Diseases, Children's Hospital Bambino Gesù, University of Rome Tor Vergata, Italy.
Insights
The CCR5 delta32 gene deletion is linked to slower HIV-1 disease progression in children. This genetic marker may help identify children who do not need immediate antiretroviral treatment.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- The CCR5 delta32 gene deletion is associated with reduced HIV-1 infection risk and delayed disease progression in adults.
- Understanding this mutation's role in pediatric HIV-1 is crucial for disease management.
Purpose of the Study:
- To investigate the impact of the CCR5 delta32 gene deletion on HIV-1 disease progression in children.
- To assess the CCR5 delta32 mutation's correlation with mother-to-child HIV-1 transmission and disease outcomes.
Main Methods:
- Polymerase chain reaction was used to genotype 301 HIV-1 infected, 262 HIV-1 exposed-uninfected, and 47 HIV-1 unexposed-uninfected children.
- HIV-1 infected children were classified as rapid or delayed progressors, including long-term non-progressors (LTNP).
- Viral phenotype analysis was performed on 45 delayed progressors.
Main Results:
- No association was found between CCR5 delta32 and mother-to-child HIV-1 transmission.
- The CCR5 delta32 deletion was significantly more frequent in long-term non-progressors (LTNP) compared to delayed and rapid progressors.
- In children with the CCR5 delta32 mutation, MT-2 tropic viruses correlated with severe immune suppression, while MT-2 negative viruses correlated with LTNP status.
Conclusions:
- The CCR5 delta32 mutation is associated with delayed HIV-1 disease progression in children.
- The CCR5 delta32 mutation may serve as a predictive marker for identifying children with slower disease progression.
- Identifying children with delayed progression could help guide decisions regarding the initiation of antiretroviral therapy.
Background:
A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults.
Materials And Methods:
To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors.
Results:
No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010).
Conclusions:
Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.