Abstract
Background and Aims: HLA-diversity is a major host genetic risk factor in infectious diseases. In particular, several studies have described associations between distinct HLA alleles and outcomes of HCV and HIV infection. The objective of this study was to analyse the distribution of HLA Class I alleles in HIV/HCV co-infected individuals in order to identify HLA-disease associations that reflect the impact of this dual infection. Methods: Clinical data from 1110 Caucasian patients (HCV: n =477, HIV: n =181, HIV and HCV: n =346, healthy controls: n = 106) were retrieved by retrospective chart review. HLA-A and B allele distribution were determined by molecular methods (SSO and SSP) with HLA-resolution reduced to the 2-digit level to enable uniform comparisons. Fisher’s exact test and Chi-square tests with Yates correction for multiple testing were applied for statistical analysis. Results: Patients with HCV mono-infection were significantly older than patients in each other group (p < 0.001). MSM was the predominant risk factor for HIV infection (52%), while most HIV/HCV and HCV-infected patients had been infected via blood exposure (83%). The frequency of HLA alleles HLA-A*30 (p =0.023), HLA-B*08 (p =0.003), HLA-B*39 (p =0.003), and HLAB*49 (p =0.032) did not differ between the patient groups but was significantly reduced in infected patients as compared to healthy controls irrespective from the underlying type of infection. In contrast, HLA-B*57, which is assumed to increase chances of spontaneous HCV resolution and delay HIV progression, was selectively increased in patients with HIV mono-infection (13%) as compared to each other group (healthy controls: 9%, HIV/HCV and HCV mono-infection: 6% each; p =0.022). Conclusion: Reduced detection rates in HIVor HCV-monoand HIV/HCV co-infected patients indicate that alleles HLA-A*30, HLAB*08, HLA-B*39, and HLA-B*49 carry a poor prognosis but do not reflect interactions between HIVand HCV-infections. Patients with blood-borne infections usually acquire HCV first and HIV later on. Thus, finding a high HLA-B57 carrier rate in HIV+ patients but in none of the other groups indicates a protective role of this allele for both HIV and HCV infection. Taken together long-term exposure of Caucasian patients to HIV and HCV infection seems to induce subtle footprints in their HLA class I repertoire.
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