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Treatment of HIV/AIDS infection with C-C antagonists What is the role of chemokine receptor status?



Treatment of HIV/AIDS infection with C-C antagonists What is the role of chemokine receptor status?



Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 41: 347



Background: Some of the new antiretroviral medications are targeted against C-C chemokine protein receptors CCR5 (SCH-C, TAK-779, AOP-RANTES, met-RANTES, PRO140, PRO367) or CXCR4 (AMD-3100, SDF-1alpha, T-7). Genes coding these proteins can be damaged due to mutations, resulting in poor function or reduced number of such receptors. Mutations in two C-C receptors genes are described: four main allelic variants of the CCR5-gene - deletion of 32-bp, deletion 1-bp, deletion 1-bp with ARG223GLN substitution, polymorphism with ALA335VAL substitution, and VAL64ILE polymorphism of the CCR2-gene. The truncated receptor did not allow fusion with C-C antagonists. Detection of the most frequent allelic variants of known mutations should precede the start of the treatment with C-C antagonists. Methods: 110 HIV-positive (23 female) residents of Czech Republic were included in the study. Genomic DNA samples were amplified using a novel simplified PCR method for 32-bp deletion of CCR5-gene detection with new primer pair yielding a 250-bp product. Amplification product was electrophoretically separated and visualized in UV light. Results: 32-bp heterozygous deletion was observed in 21 of 110 (19%) HIV-positive patients, comparable with non-HIV population. Conclusions: Unexpectedly, we have found relatively high number of heterozygous 32-bp deletions among tested persons in HIV-positive group. Therefore, we suggest to test HIV-positive patients for the presence of deletion of 32-bp for CCR5 gene before the start of the treatment with C-C antagonists. The influence of the chemokine receptor status on the treatment with C-C antagonists should be subject to further research.

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