Interferon-gamma, interleukin-10 and adiponectin as disease progression markers in hiv-1 and tuberculosis co-infected non-injection drug users from Mombasa, Kenya
Nebere, Saraphine Nekesa
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Both HIV and TB as well as substance use cause profound dysregulation in the production of inflammatory cytokines such as adiponectin, interleukin-10 (IL-10) and interferon-gamma (IFN-γ). Although there are marked immunologic alterations in HIV and TB co-infected patients, IFN-γ, IL-10 and adiponectin levels, and their association with clinical correlates of disease such as CD4 counts, HIV-1 viral loads and BMI has not been examined in Kenyan HIV and TB co-infected non-injection substance using patients. Therefore, this cross-sectional study determined circulating IFN-γ, IL-10 and adiponectin levels in substance users at Bomu hospital, Mombasa, Kenya. The study groups included; HIV-1 and TB co-infected antiretroviral treatment (ART)-naive (n=12) and -exposed (n=9); HIV-1 mono-infected ART-naive (n=21) and ART-exposed (n=6); TB mono-infected (n=5); and uninfected substance users (n=32); and healthy controls (n=27). Demographic, anthropometric and clinical measures were recorded at enrolment of the study participants. Venous blood was collected from each participant followed by centrifugation to obtain plasma that was stored at -800C until used for cytokine and viral load measurements. CD4+ T cell counts were enumerated using a FACSCaliburTM flow cytometer on whole blood while Abbot m200-RT-PCR was used to determine HIV-1 RNA copies. TB was assessed on sputum using acid-fast staining procedure while plasma cytokine concentrations were measured using a sandwich ELISA. Statistical comparisons across-groups for continuous variables were performed using non-parametric ANOVA (Kruskal Wallis) tests followed by post-hoc Dunn’s corrections for multiple comparisons. Spearman’s rank correlation tests were used to determine the association of IFN-γ, IL-10 and adiponectin with viral loads, CD4+ T cell counts and body mass index (BMI). IFN-γ levels differed across the study groups (P<0.0001) and were higher in the HIV-1/TB co-infected ART-naive (P<0.001) and -exposed (P<0.001), TB mono-infected (P<0.001) and uninfected (P<0.001) substance users compared to healthy controls indicating influence of substance use on IFN-γ production. IL-10 levels were different across groups (P=0.035) and were higher in the uninfected substance users (P<0.05) in comparison with healthy individuals suggesting that drugs stimulate IL-10 release. On the other hand, adiponectin levels differed significantly across study groups (P<0.036), and were lower in HIV-1 mono-infected ART-naive patients (P<0.05) relative to HIV and TB co-infected ART-naïve patients, un-infected non-IDUs and healthy controls depicting adverse effect of HIV on adiponectin production. Spearman rank correlation tests indicated that IFN-γ was positively associated with the CD4+ T cell counts (ρ=0.900; P=0.037) in TB mono-infected signifying that CD4+ T cells produce IFN-γ during TB infection. Adiponectin was positively associated with HIV-1 viral load among ART-naive HIV-1 mono-infected patients (ρ=0.829; P=0.042) suggesting a link between adiponectin and HIV-1 disease progression. Altogether, these results suggest that substance use promotes increased IFN-γ and IL-10 production in HIV and TB co-infected patients that may trigger disease progression in this population. Therefore, drug use screening should be adopted in HIV-1/TB-care centres for effective management of the co-infected patients. Further research should be carried out to ascertain the role of adiponectin in HIV/TB pathogenesis.