Clinical Spectrum, Risk Factors and Outcome of Immune Reconstitution Inflammatory Syndrome in Patients with Tuberculosis–HIV Coinfection

Abstract

TB-IRIS was a frequent reason for clinical deterioration among patients with TB commencing ART but was not a primary contributor to mortality. Patients with advanced CD4 depletion and anaemia were at increased risk of TB-IRIS. Some patients developed late-onset TB-IRIS and/or a recurrent TB-IRIS episode.

Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis

“…An increased risk of both PR and IRIS has been identified in patients with disseminated or extrapulmonary disease, who are considered to have higher bacillary/antigen loads, although this may not necessarily be the case in patients with apparently isolated peripheral lymph node disease. 1,8,17,18,32 The risk of paradoxical IRIS has been demonstrated to be highest when HAART is initiated early during antimycobacterial therapy, at a point when mycobacterial loads are still nearmaximal. This risk has been confirmed in large RCTs seeking to optimize the timing of HAART initiation.…”

“…In HIV-seronegative individuals, low baseline lymphocyte counts at the time of TB diagnosis are associated with an increased risk of developing PR, 2,8 whilst in HIV-seropositive individuals, low CD4+ T cell counts have been related to subsequent IRIS in a range of studies. 13,18,23,24,34 Advanced HIV disease has also been identified as a risk factor for IRIS, consequent on high pre-HAART HIV-1 viral loads. 34 Given that a relationship between active TB and lymphopenia has been reported, 42 and it is suggested that active TB is associated with a degree of immunodeficiency, 43 one could hypothesize that a baseline immunodeficient phenotype in both HIV seronegative and seropositive individuals is implicated in the development of both PR and IRIS.…”

“…27 Case definitions for paradoxical and unmasking TB-IRIS are still debated, 15,28 but consensus definitions for use in clinical and research settings have now been validated in prospective studies. 18,28,29 The consensus definition for paradoxical TB-IRIS is summarized by a confirmed diagnosis of TB with a positive initial response to antimycobacterial therapy, onset of defined inflammatory clinical manifestations within 3 months of subsequently commencing HAART, with exclusion of plausible alternative explanations for this clinical deterioriation. 28 Wider pan-pathogen IRIS case definitions have similarly used temporal criteria in relation to HAART initiation and identification of inflammatory manifestations.…”

“…16 The occurrence of unmasking TB-IRIS is thought to be lower than paradoxical TB-IRIS, 15 with estimates varying between 1.4% and 23%. 14,[17][18][19] It is also suggested that HIV-seropositive individuals with active TB may have an increased incidence of PR when commencing antimycobacterial therapy, compared to HIV-seronegative individuals. 6,17 The clinical features of TB-IRIS are similar to those of PR, commonly including fever, while other manifestations reflect the baseline form of TB disease, such as lymph node swelling and deterioration of respiratory symptoms.…”

Tobacco smoking effect on HIV-1 pathogenesis: role of cytochrome P450 isozymes

“…Such patients undergo a unique and exuberant recovery characterized clinically by an inflammatory syndrome which is excluded by a typical drug reaction. In a recent study by Worodria et al [95], a total of 21% of 254 HIV-1/TB co-infected patients developed TB-IRIS within 2 weeks of starting HAART. It occurs in between 8 and 43% of co-infected patients and causes significant patient morbidity [96].…”