Introduction.
The human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) are major threats to public health. Presumably, because of the similar transmission routes (e.g., drug injection), co-infection with HIV and HCV is very common [1], [2]. It is estimated that over 5 million people worldwide live with chronic HIV/HCV co-infection. However, the prevalence of HIV/HCV co-infection largely varies in different risk groups, with an especially high rate among HIV-positive injective drug users (IDUs) [3].

In China, over 90% of HIV-positive IDUs are co-infected with HCV [1].

Several studies have explored the viral interactions between HCV and HIV infection. However, little is known either about the molecular basis of the interactions or the consequences of host responses. It has been shown that HIV co-infection significantly affected the natural history of hepatic fibrosis in HCV-infected persons[4]. Obviously, a concomitant HIV infection increased the evolution of HCV quasispecies, the level of viremia, and the extrahepatic viral reservoirs [5], [6], [7]. These factors decreased the effects of anti-HCV treatment. Cytokines (IFN-γ, TNF-α and IL-4, etc.) in peripheral blood mononuclear cells (PBMC) and dehydroepiandrosterone sulphate in plasma were greatly decreased in HIV/HCV-co-infected patients [8], [9]. In addition, HIV viral loads displayed additive effects on HCV-triggered mitochondrial DNA depletion, which seems to be associated with the nucleoside analogs' toxicities [10], [11]. However, the impact of HCV infection on HIV/AIDS was not conclusive, even controversy [12], [13]. Some evidence suggests that the increased HCV viral load was associated with AIDS progression. HCV seems to impair the immune reconstitution, leading to an increased rate of AIDS-related death [14], [15]. In other studies, however, HCV did not show any significant effect on HIV-associated disease [16].

Although highly active antiretroviral treatment (HAART) is very successful for treating HIV mono-infection, its impact on HCV has been debated [17], [18]. Sulkowski et al. showed that the co-infected individuals experienced an increased risk of hepatotoxicity after HAART [19]. Similarly, the toxicities of interferon-based HCV therapies were also exacerbated in HIV/HCV-co-infected patients with a higher rate of relapses [20], [21]. Therefore, the management of HIV/HCV-co-infected patients is still a major challenge. The underlying mechanisms of highly increased mortality remain elusive.

CD8+ T cells play a crucial role in the eradication of viruses and the infected target cells. It has been shown that the high viral load of HCV in HIV/HCV-co-infected patients was associated with profound defects in HCV-specific CD8+ T cell responses [22]; however, the gene expression profiles have been monitored only in the total T cells or in the liver biopsy in HIV- or HCV-mono-infected patients [23], [24]. To the best of our knowledge, no-one has reported the global gene expression profiles in HIV/HCV-co-infected individuals. In this study, we investigated the global gene expression patterns of CD8+ T cells in the HIV/HCV-co-infected and the HIV- or HCV-mono-infected treatment-naïve individuals without symptoms of liver disease and AIDS.

Abstract.
Background
Co-infection with HIV and HCV is very common. It is estimated that over 5 million people are co-infected with HIV and HCV worldwide. Accumulated evidence shows that each virus alters the course of infection of the other one. CD8+ T cells play a crucial role in the eradication of viruses and infected target cells. To the best of our knowledge, no one has investigated the gene expression profiles in HIV/HCV-co-infected individuals.

Methodology
Genome-wide transcriptomes of CD8+ T cells from HIV/HCV-co-infected or mono-infected treatment-naïve individuals were analyzed by microarray assays. Pairwise comparisons were performed and differentially expressed genes were identified followed by quantitative real-time PCR (qRT-PCR) validation. Directed Acyclic Graphs (DAG) from Web-based Gene SeT AnaLysis Toolkit (WebGestalt) and DAVID bioinformatics resources 6.7 (the Database for Annotation, Visualization, and Integrated Discovery) were used to discover the Gene Ontology (GO) categories with significantly enriched gene numbers. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were also obtained by using WebGestalt software.

Results and Conclusions
A total of 110, 24 and 72 transcript IDs were shown to be differentially expressed (> 2-fold and p<0.05) in comparisons between HCV- and HIV-mono-infected groups, HIV/HCV-co-infected and HIV-mono-infected groups, and HIV/HCV-co-infected and HCV-mono-infected groups, respectively. In qRT-PCR assay, most of the genes showed similar expressing profiles with the observation in microarray assays. Further analysis revealed that genes involved in cell proliferation, differentiation, transcriptional regulation and cytokine responses were significantly altered. These data offer new insights into HIV/HCV co-infections, and may help to identify new markers for the management and treatment of HIV/HCV co-infections.