CYTOKINES LEVELS AND THEIR RELATIONSHIP WITH CLINICAL CORRELATES IN HUMAN IMMUNODEFICIENCY VIRUS/HEPATITIS C CO- INFECTED DRUG USERS FROM MOMBASA COUNTY, KENYA

Human immunodeficiency virus-1(HIV-1) and hepatitis C virus (HCV) co-infection are two rapidly growing epidemics and health concerns strongly driven by injection drug use (IDU) in Kenya and the entire world. Inflammatory cytokines are important mediators of the host response to HIV-1 and HCV infections including injection drugs. However, the molecular interaction between HIV-1 and HCV co-infection and correlation with injection drug use is largely undefined. Therefore, this cross-sectional study determined plasma levels of interferon (IFN)-, interleukin (IL)-10, adiponectin and their association with CD4+ T cell count, HIV-1 viral load and basal metabolic index (BMI) in HIV-1 and HCV mono-infected antiretroviral (ART)-naive (n=18) and -exposed (n=38); and co-infected ART-naive (n=5) and -exposed (n=14); and uninfected (n=24) IDUs and healthy controls (n=27). One hundred and thirty five injection drug users and 27 healthy controls were recruited from Bomu Medical Center, Mombasa, Kenya through outreach and respondent driven sampling methods. Social demographic information including drug use histories were collected from the study subjects upon enrolment into the study through structured interview schedules with openand closedended questions. Plasma cytokines levels were determined using Enzyme linked Immunosorbent assay (ELISA) technique, CD4 T cell count were enumerated using FacsCalibur TM flow cytometry, HIV-1 viral load through polymerase chain reaction (PCR), and HIV-1 and HCV infections determined by rapid sero-diagnosis. Interferon (IFN)- levels differed across-group (P<0.0001) and were significantly elevated in HIV-1 mono-infected ART-exposed and uninfected individuals relative to healthy controls (p<0.0001). Interleukin (IL)-10 levels also varied across-group (P<0.0001) and were higher in HIV-1 and HCV co-infected ART-exposed, HCV mono-infected and uninfected IDUs compared to healthy controls (p<0.0001). Adiponectin levels varied across-group (p<0.0001) and were significantly higher in HCV monoinfected compared to HIV-1 mono-infected ART-exposed or -naive (p<0.0001). Interferon- (IFN-)/IL-10 ratio differed across-group (P<0.0001) and was increased in HIV-1 and HCV coinfected ART-exposed, HCV mono-infected, HIV-1 mono-infected ART-exposed, and uninfected groups relative to healthy controls (P<0.0001). Interferon- (IFN-) was correlated with BMI (=-0.628; P=0.029) in HIV-1 and HCV co-infected ART-exposed, viral load (=0.998; P=0.004) in HIV-1 and HCV co-infected ART-naive, CD4+ T cell count (=-0.393; P=0.018) in HCV mono-infected IDUs. Interferon- (IFN-) was also correlated with IL-10 in HIV/HCV co-infected ART-exposed (r=0.711, p=0.010), HIV mono-infected ART-naive (r=0.616, p=0.011), healthy controls (r=0.877, p< 0.0001), adiponectin (r= -0.422, p=0.013) in ART-exposed HIV-1 mono-infected IDUs. Taken together, these results suggest profound dysregulation in IFN- and IL-10 production that is associated with clinical outcomes in both HIV-1 and HCV monoand co-infected and uninfected IDUs. The implications of these findings include their utility in initiation and monitoring of treatment in IDUs.