Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy

Worodria, William; Loembé, Marguerite Massinga; Mazakpwe, Doreen; Luzinda, Kenneth; Menten, Joris; Leth, Frank van; Mayanja‐Kizza, Harriet; Kestens, Luc; Mugerwa, Roy D.; Reiss, Peter; Colebunders, Robert

doi:10.1097/qai.0b013e3182255dc2

Cited by 63 publications

(69 citation statements)

References 33 publications

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“…Treatment success did not differ by HIV status, a fi nding similar to a study from Zimbabwe. 18 However, contrary to fi ndings from other studies, 23,24 treatment success among patients who received ART were not different from those who did not receive ART. The same was observed regarding the infl uence of CPT on treatment outcomes.…”

Section: Public Health Action Treatment Outcomes Of Tb Retreatment Cacontrasting

confidence: 56%

Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda

Nakanwagi-Mukwaya¹,

Reid²,

Fujiwara³

et al. 2013

public health action

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Section: Public Health Action Treatment Outcomes Of Tb Retreatment Cacontrasting

confidence: 56%

Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda

Nakanwagi-Mukwaya¹,

Reid²,

Fujiwara³

et al. 2013

public health action

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“…Known risk factors of TB-IRIS include a low CD4 count, high TB-antigen burden and short interval between initiation of TB treatment and ART [9], [10]. The pathogenesis of TB-IRIS remains largely unclear, although there are clear signs of tissue-destructive inflammation during immune reconstitution (reviewed in [11], [12]).…”

Section: Introductionmentioning

confidence: 99%

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

et al. 2014

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Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. Methods In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. Results Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS.

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“…High mortality has been reported among HIV-positive people treated for active TB (HIV/TB patients), particularly in patients with advanced disease [1,2]. Combination antiretroviral therapy (cART) treatment is associated with a marked reduction of mortality in HIV/TB patients, although access and availability are far from equal around the world [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Podlekareva

Panteleev²,

Grint

et al. 2013

Eur Respir J

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Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death.This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (,3 months, 3-12 months or .12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three-to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died ,3 months, 3-12 months or .12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p,0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death.Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region. @ERSpublications High TB-related death rates in HIV patients in Eastern Europe require measures to improve their clinical management

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Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy

Cited by 63 publications

References 33 publications

Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda

Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals, Uganda

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

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