Abstract
Association between hepatitis C virus (HCV) quasispecies and treatment outcome among patients with chronic hepatitis C has been the subject of many studies. However, these studies focused mainly on viral variable regions (E1 and E2) and usually did not include human immunodeficiency virus (HIV)-positive patients. The aim of the present study was to analyze heterogeneity of the 5'untranslated region (5'UTR) in HCV/HIV coinfected patients treated with interferon and ribavirin. The HCV 5’UTR was amplified from serum and peripheral blood mononuclear cells (PBMC) samples in 37 HCV/HIV coinfected patients treated for chronic hepatitis C. Samples were collected right before treatment, and at 2, 4, 6, 8, 12, 20, 24, 36, 44, 48, 60, and 72 weeks. Heterogeneity of the 5'UTR was analyzed by single strand conformational polymorphism (SSCP), cloning and sequencing. Sustained virological response (SVR) was achieved in 46% of analyzed HCV/HIV co-infected patients. Stable SSCP band pattern was observed in 22 patients (62.9%) and SVR rate among these patients was 23%. Decline in the number of bands and/or shift in band positions were found in 6 patients (17.1%), 5 (83%) of whom achieved SVR (p=0.009). A novel viral genotype was identified in all but one of these patients. In 5 of these 6 patients a new genotype was dominant. 5'UTR heterogeneity may correlate with interferon and ribavirin treatment outcome. In the analyzed group of HCV/HIV coinfected patients, viral quasispecies stability during treatment favored viral persistence, whereas decrease in the number of variants and/or emergence of new variants was associated with SVR. Among injection drug users (IDU) patients, a new genotype may become dominant during treatment, probably due to the presence of mixed infections with various strains, which have different susceptibility to treatment.
Highlights
Due to similar routes of transmission, coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is common [1, 2]
The Sustained virological response (SVR) rate in patients infected with HCV genotype 3a was 70%, whereas among patients infected with genotypes 1 or 4 only 37.5% cleared infection (Table 2)
No significant association was found between SVR and sex, age, IL28B genotype, baseline HCV and HIV viral load, HCV genotype, CD4+ cell count and highly active antiretroviral therapy (HAART) in univariate analysis, some positive trends were noted with respect to female gender (p = 0.078), age under 30 (p = 0.063), HCV genotype 3a (0.083) and no HAART treatment (p = 0.078); (Table 2)
Summary
Due to similar routes of transmission, coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is common [1, 2]. 10–15% of the 35 million HIV-infected individuals worldwide are coinfected with HCV, while among 150 million of humans infected with HCV, the HIV coinfection rate is close to 3%. Patients with dual HCV/HIV infection are at a higher risk of developing decompensated liver disease and hepatocellular carcinoma [4,5,6]. As a consequence of introduction of highly active antiretroviral therapy (HAART) and lowering the overall HIV-related death rate, liver disease became the leading cause of death among HIV-positive patients [7]. Despite the somewhat lower rate of treatment success, it is widely accepted that HCV/HIV coinfected patients are likely to benefit from treatment regimens aimed at HCV eradication [8]
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