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 coinfected
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 monoinfected
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.