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Epidemiology and Natural History of HIV/HCV Co-Infection
Tuesday, 1:30 - 3:30 pm
Background: Chemokines and their receptors are crucial for the immune response in HIV and HCV infection. The natural course of HIV infection is altered by RANTES gene polymorphisms through up- or down-regulation of this chemokine. As RANTES is involved in the recruitment of HCV-specific T cells to the liver in hepatitis C virus infection such mutations may also influence the natural course of chronic HCV and especially HCV/HIV co-infection.
Methods: We determined the RANTES-403 (G -->A), RANTES-28 (C -->G) and RANTES-IN1.1 (T -->C) gene polymorphisms using real time PCR and hybridization probes in patients with HIV infection (n = 85), HCV infection (n = 130), HIV/HCV co-infection (n = 121), and 109 healthy blood donors. Each group was stratified into according RANTES genotypes, and the resulting subsets were compared with respect to HIV and HCV loads.
Results: The frequencies of RANTES-403 A (15.4%), RANTES-28 G (1.7%), and RANTES-IN1.1 C (12.0%) alleles were lower in HCV/HIV co-infected patients than in HIV mono-infected individuals (28.2%, p = 0.002; 5.4%, p = 0.048; 19.0%, p = 0.066), but did not differ from HCV-infected patients (19.6%; 1.5%; 11.5%) and healthy controls (15.1%; 2.8%; 11.0%). HIV-infected patients with the RANTES-403 G/G showed a trend to higher HIV loads compared to RANTES-403 A/A (p = 0.067). In contrast, HCV viral loads were significantly higher in HCV/HIV co-infected patients with RANTES-403 G/A than in RANTES-403 A/A patients (p = 0.045).
Conclusions: The RANTES-403 A, RANTES-28 G and RANTES-IN1.1 C alleles are more frequent in HIV mono-infection than in HCV/HIV coinfection or healthy controls. Thus, RANTES polymorphisms seem to be of less importance in HCV/HIV co-infection. As HCV-NS5A and HCV-core proteins are known to augment RANTES promoter activity in vitro, the low frequency of RANTES polymorphisms in HCV/HIV coinfection may indicate, that influence of these mutations in this setting is neutralized by the effect of HCV infection on RANTES transcription.
Keywords: Hepatitis C virus co-infection; rantes polymorphism; chemokine