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

Abstract

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.

DNA methylation signatures of illicit drug injection and hepatitis C are associated with HIV frailty

“…IDU and HCV may worsen HIV outcomes by introducing or amplifying proinflammatory processes, such as cytokine release 4 – 6 . Markers of immune activation such as CD38 expression on CD8 + T cells and soluble CD14 were significantly increased in IDU as compared to in non-IDU subjects 7 , 8 . HCV infection further enhances the activation of immune function in IDU 5 .…”

Changes in opiate and stimulant use through 10 years: The role of contextual factors, mental health disorders and psychosocial factors in a prospective SUD treatment cohort study

“…Twenty treatment facilities were purposively selected for patient recruitment. The facilities represented the most common treatment programmes in Norway; (residential treatment, specialised therapeutic outpatient teams and Opioid Maintenance Treatment (OMT)) (see also [ 27 ], [ 28 ], [ 29 ]). The chosen geographical area for recruitment of facilities was the capital of Norway and surroundings (i.e., the greater Oslo region), where these treatment modalities were available and the illicit drug problems are the most prevalent.…”

“…Cumulatively, there were 11 (2.40%), 19 (4.20%), 59 (13.10%) and 72 (16%) deceased at the four follow-up interviews. Some differences between the deceased and non-deceased patients were found [ 28 ]. The patients who died during the follow-up years had a slightly higher number of nonfatal overdoses prior to index treatment; they had more years with alcohol abuse and spent longer time in prison than the non-deceased.…”

Brief Report: The Relationship Between Injection Drug Use Risk Behaviors and Markers of Immune Activation

“…Those who met the criteria were telephoned the night before their appointment as a reminder. At the scheduled date they came to the research hospital setting where a flexible sigmoidoscopy with biopsy was performed after phlebotomy for immunologic evaluations (see Mehandru et al 4 for description of procedure). Cash incentives were provided for both the screening visit and the sigmoidoscopy with biopsy.…”

“…3,4 Increasing our understanding of the factors contributing to this heightened immune activation, which has been associated with progression of chronic disease and disability, 5,6 can lead to better health outcomes for PWID.…”