Polymorphisms of Cx(3)CR1 and CXCR6 receptors in relation to HAART therapy of HIV type 1 patients
A M Passam1, G Sourvinos, E Krambovitis
1Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
Insights
Certain chemokine gene variations impact HIV treatment effectiveness. Specific CX3CR1 alleles improve immune response to HAART, while the CXCR6-3K allele is linked to faster virologic failure in HIV-1 patients.
Area of Science:
- Immunogenetics
- Virology
- Pharmacogenomics
Background:
- Specific chemokine gene polymorphisms, including CXCR6-3E/K, In1.1T/C, H7 haplotype, and CX(3)CR1 variants (V249I, T280M), are known to influence HIV infection progression.
- Understanding these genetic factors is crucial for predicting and optimizing treatment outcomes in HIV-1 patients.
Purpose of the Study:
- To investigate the impact of selected chemokine polymorphisms on the immunologic and virologic response to highly active antiretroviral therapy (HAART) in HIV-1 infected individuals.
- To identify genetic markers that predict treatment success or failure in the context of HAART.
Main Methods:
- A cohort of 143 HIV-1 patients receiving HAART was studied.
- Kaplan-Meier survival analysis was employed to assess time-to-event endpoints, including time to undetectable viral load (<50 copies/ml), duration of viral suppression, CD4 count changes (elevation above 200 or 500 cells/microl, or reduction below baseline).
Main Results:
- Patients with CX(3)CR1-249I or CX(3)CR1-280M alleles demonstrated an improved immunologic response to HAART.
- Conversely, the presence of the CXCR6-3K allele was associated with a more rapid virologic failure after initial viral load suppression with HAART.
- No significant effect on HAART response was observed for the In1.1T/C polymorphism or the H7 haplotype.
Conclusions:
- CX(3)CR1 polymorphisms (V249I and T280M) are associated with better immune reconstitution during HAART for HIV-1.
- The CXCR6-3K allele may predict a poorer virologic outcome in HIV-1 patients undergoing HAART.
- These findings highlight the role of specific chemokine gene variants in modulating the response to antiretroviral therapy.
Abstract:
The chemokine polymorphisms CXCR6-3E/K, In1.1T/C, H7 haplotype, CX(3)CR1-V249I, and CX(3)CR1-T280M have been shown to affect the course of HIV infection. We studied their influence on immunologic and virologic response to HAART in a group of 143 HIV-1 patients. We performed Kaplan-Meier analysis using the following end-point criteria: (1) time from HAART initiation to undetectable viral load (VL < 50 copies/ml), (2) maximum duration of viral suppression, (3) time from HAART administration until CD4 elevation above 200 cells/microl for patients with baseline CD4 below 200 cells/microl and above 500 cells/microl for patients with baseline CD4 between 200 and 500 cells/microl, respectively, and (4) time from HAART initiation until CD4 reduction below baseline values. Our results revealed an improved immunologic response to HAART in patients with the CX(3)CR1-249I or CX(3)CR1-280M allele. On the contrary, patients with initial VL suppression due to HAART showed a faster virologic failure in the presence of the CXCR6-3K allele. The In1.1T/C polymorphism and H7 haplotype did not reveal any specific effect on HAART response.
