Abstract
ObjectiveInjection drug use (IDU) remains a major risk factor for HIV-1 acquisition. The complex interplay between drug use, non-sterile injection, and Hepatitis C remains poorly understood. We conducted a pilot study to determine the effect of IDU on immune parameters among HIV-uninfected and -infected individuals. We hypothesized that IDU could further augment immunological changes associated with HIV-1 infection, which could in turn affect HIV pathogenesisMethodsHIV-uninfected and -infected subjects with IDU, and non-IDU controls were recruited to obtain socio-demographic and drug-related behaviours. Blood (PBMC) and mucosal (MMC) mononuclear cells were analysed for cellular markers of immune activation (CD38 and Ki67). Serum ELISA was performed to determine levels of soluble CD14, a marker of immune activation.ResultsNo significant quantitative differences in CD4+ and CD8+ T cell levels were observed between IDU and non-IDU subjects when accounting for the presence of HIV-1 infection. However, increased levels of cellular and soluble markers of immune activation were documented in cells and plasma of HIV-uninfected IDU subjects compared to non-injectors. Additionally, sharing of injection paraphernalia was related to immune activation among HIV-uninfected IDU subjects.ConclusionIDU, with or without HIV-1 infection, results in a significant increase in immune activation in both the peripheral blood and the GI tract. This may have significant impact on HIV transmission, pathogenesis, and immunologic responses to combination antiviral therapy. This study provides compelling preliminary results which in turn support larger studies to better define the relationship between IDU, infection with HIV-1, co-infection with Hepatitis C and immunity.
Highlights
The devastating consequences of untreated HIV-1 infection on the human immune system have spurred investigations aimed at better understanding disease pathogenesis
No significant quantitative differences in CD4+ and CD8+ T cell levels were observed between injection drug users (IDU) and non-IDU subjects when accounting for the presence of HIV-1 infection
Increased levels of cellular and soluble markers of immune activation were documented in cells and plasma of HIV-uninfected IDU subjects compared to non-injectors
Summary
The devastating consequences of untreated HIV-1 infection on the human immune system have spurred investigations aimed at better understanding disease pathogenesis. More recently it has been suggested that there is selective depletion of the Th17 cells from the GI tract- and that the loss of these cells may result in loss of mucosal integrity, translocation of microbial products, immune activation and subsequent CD4+ T cell loss [7] These findings have emerged primarily from studying non-injection drug using HIV-1 infected cohorts, predominantly men who have sex with men (MSM). In order to expand the findings derived from studies of MSM to others at risk and infected populations, it is essential to examine these relationships for injection drug users (IDUs) of both sexes It remains unknown whether active injection drug use when superimposed on HIV-1 infection accelerates the loss of CD4+ T cell in the GI tract and periphery due to increased levels of activation due to non-specific antigenic stimulation
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