Behavioural, Mucosal and Systemic Immune Parameters in HIV-infected and Uninfected Injection Drug Users

Objective: Injection 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 pathogenesis Methods: HIV-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. Results: No 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. Conclusion: IDU, 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.