Abstract
Tuberculosis (TB) and HIV have profound effects on the immune system, which can lead to the activation of viral replication and negatively regulate the activation of T cells. Dysregulation in the production of cytokines necessary to fight HIV and M. tuberculosis may ultimately affect the results of the treatment and be important in the pathogenesis of HIV infection and TB. This work presents the results of a study of the expression of pro- and anti-inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-1RA) in drug-naïve patients with dual infection of HIV/TB at the late stages of HIV-infection, with newly diagnosed HIV and TB, and previously untreated HIV in the process of receiving antiretroviral (ART) and TB treatment vs. a cohort of patients with HIV monoinfection and TB monoinfection. The study revealed that during a double HIV/TB infection, both Th1 and Th2 immune responses are suppressed, and a prolonged dysregulation of the immune response and an increased severity of the disease in pulmonary/extrapulmonary tuberculosis is observed in HIV/TB co-infection. Moreover, it was revealed that a double HIV/TB infection is characterized by delayed and incomplete recovery of immune activity. High levels of IL-6 were detected in patients with HIV/TB co-infection before initiation of dual therapy (2.1-fold increase vs. HIV), which persisted even after 6 months of treatment (8.96-fold increase vs. HIV), unlike other cytokines. The persistent enhanced expression of IL-6 in patients with dual HIV/TB co-infection allows the consideration of it as a potential marker of early detection of M. tuberculosis infection in HIV-infected individuals. The results of multivariate regression analysis showed a statistical trend towards an increase in the incidence of IRIS in patients with high IL-1Ra levels (in the range of 1550–2500 pg/mL): OR = 4.3 (95%CI 3.7–14.12, p = 0.53), which also allows IL-1Ra to be considered as a potential predictive biomarker of the development of TB-IRIS and treatment outcomes.
Highlights
The goal of this work was to study the expression of a number of pro-inflammatory and anti-inflammatory cytokines in patients with double HIV/TB infection, newly diagnosed with HIV and TB, and previously untreated HIV before and during the process of receiving antiretroviral/anti-tuberculosis therapy and to identify possible potential predictive markers that allow clinicians to foresee the development of the disease and evaluate the effectiveness of therapy
Patients with HIV/TB were naïve for antiretroviral therapy (ART) and anti-tuberculosis therapy, HIV-positive patients were naïve for ART, and TB patients were naïve for antituberculosis therapy
A total of 356 people participated in the study: 116 patients with HIV/TB co-infection
Summary
The imbalance of cytokine secretion in HIV infection affects the function of the immune system and the course of the disease, increasing or suppressing. Despite effective antiretroviral therapy (ART), there is evidence of persistent viral production and persistent immune activation in HIV-infected individuals [6,7,8]. It has been shown that persistent immune activation during viral load suppression correlates with a high risk of developing concomitant diseases not related to AIDS, including metabolic syndrome [9,10,11,12], cardiovascular diseases [9,13,14,15], neurocognitive disorders [16,17,18,19], and malignant neoplasms [20,21,22,23] and is directly associated with increased mortality [24,25]
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