Immunologic Markers as Predictors of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in HIV and Tuberculosis Coinfected Persons in Thailand

Abstract

This study analyzes immunologic markers to predict and diagnose tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV and TB coinfected adults who initiated antiretroviral therapy (ART) in Thailand. T helper 1 cytokines interleukin (IL)-2, IL-12, and interferon-gamma (IFN-g) levels in response to PPD and RD1 antigens were assessed prior to ART, at weeks 6, 12, and 24 of treatment, and at time of TB-IRIS. Of 126 subjects, 22 (17.5%) developed TB-IRIS; 14 (64%) subjects received steroid treatment and 3 (14%) received NSAIDs; none of the subjects died. Median interval between ART initiation and TB-IRIS development was 14 days. IFN-g, IL-2, and IL-12 responses did not differ between TB-IRIS and no TB-IRIS subjects ( p > 0.05). More research into the immunopathogenesis of TB-IRIS and diagnostic potential of cytokine markers is warranted.

Leishmaniasis as a Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-Infected Patients

“…42,43 However, the importance of specific T cells warrants further investigation, as other studies found no association between the recovery of M tuberculosis –specific T cells and tuberculosis in association with IRIS. 44,45 To date, the literature contains no reports linking the recovery of Leishmania -specific T cells with IRIS-associated leishmaniasis. It is also possible that other mechanisms could contribute to the intensity of inflammatory responses during IRIS, such as the excessive activation of innate immune cells 3 or the impairment of a regulatory T-cell response.…”

Paradoxical TB-IRIS in HIV-infected Adults: a Systematic Review and Meta-analysis

“…In this study disseminated TB was defined as TB in more than one organ or a positive blood culture for M. tuberculosis. In the multivariate analysis of a study in Thailand, extrapulmonary TB versus pulmonary TB alone increased the risk of paradoxical TB-IRIS almost ninefold (OR: 8.63; p = 0.004) [41].…”

“…Disseminated or extra-pulmonary tuberculosis was associated with TB-IRIS in 11 studies in univariate analysis [12,29,32,[40][41][42]44,52,54,55] and in five studies in multivariate analysis (see Supplementary table 1) [32,40,41,52,55]. In multivariate analysis of two studies from Asia, extra pulmonary TB increased the risk of paradoxical TB-IRIS eightfold (OR: 8.225 [32] and OR: 8.63 [40]).…”

“…More rapid reduction in viral load during early ART was associated with paradoxical TB-IRIS in two studies [27,64]. In a study of immunological predictors of TB-IRIS, a viral load decrease ≥4 log 10 copies/ml at week 12 on ART was associated with a 2.6-fold increase in odds of developing TB-IRIS [41]. The SAPiT, CAMELIA and STRIDE RCTs all reported that lower median CD4 count at ART initiation and higher baseline viral load were associated with paradoxical TB-IRISin both univariate and multivariate analyzes [15,24,55].…”

Mediators of Innate and Adaptive Immune Responses Differentially Affect Immune Restoration Disease Associated withMycobacterium tuberculosisin HIV Patients Beginning Antiretroviral Therapy

“…Clinicopathological and immunological studies suggest that mycobacterial IRD is associated with the recovery of type 1 T helper cell (Th1) responses against mycobacterial antigens, which are characterized by increased delayed-type hypersensitivity skin test or T cell interferon-g (IFN-g) responses to mycobacterial antigens [9,15,17,[23][24][25], and possibly KIR Ϫ Vd2 + TCR gd + T cell responses [24] but not with a deficiency of circulating regulatory T cells [23,25,26]. However, some studies have not demonstrated a relationship between TB-IRIS and IFN-g responses to M. tuberculosis antigens [27], and some could not demonstrate a temporal relationship with disease onset [17,23]. One possible explanation for this is the involvement of innate immune responses.…”