Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings

Abstract

The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important early complication of antiretroviral therapy (ART) in resource-limited settings, especially in patients with tuberculosis. However, there are no consensus case definitions for IRIS or tuberculosisassociated IRIS. Moreover, previously proposed case definitions are not readily applicable in settings where laboratory resources are limited. As a result, existing studies on tuberculosisassociated IRIS have used a variety of non-standardised general case definitions. To rectify this problem, around 100 researchers, including microbiologists, immunologists, clinicians, epidemiologists, clinical trialists, and public-health specialists from 16 countries met in Kampala, Uganda, in November, 2006. At this meeting, consensus case definitions for paradoxical tuberculosis-associated IRIS, ART-associated tuberculosis, and unmasking tuberculosis-associated IRIS were derived, which can be used in high-income and resource-limited settings. It is

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

“…For instance, patients coinfected with HIV and Mtb, who present low counts of CD4 + T cells, lack caseating granulomas (46,52). Immune reconstitution in these patients by antiretroviral therapy results in the increased development of lung pathology associated with TB (46,52).…”

Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial

“…Secondary outcomes were increase in CD4 cell count by more than 20% from baseline to week 48, occurrence of AIDS-defi ning events, end of tuberculosis treatment outcomes as per WHO defi nitions, occur rence of treatment-emergent adverse eff ects (TEAE), and paradoxical tuberculosis immune reconstitution infl ammatory syndrome (IRIS) within 12 weeks of start of antiretroviral therapy. 20,21 Members of the trial's scientifi c advisory board (RB and CM) validated causes of death and IRIS-tuberculosis. Adverse event terms were adopted from the medical dictionary for regulatory activities (MedDRA version 11.1).…”

Tuberculous meningitis in adults: a review of a decade of developments focusing on prognostic factors for outcome

“…The incidence of IRIS in TBM is unknown, diagnosis is difficult to establish, and it must be distinguished from other causes of neurological deterioration, such as drug resistance, other CNS opportunistic infections and stroke. Using a recently published case definition may improve recognition of this syndrome [98]. A recent randomized controlled trial showed no reduction in mortality with immediate initiation of ART; instead, the study suggests that it may be safer to defer the initiation of ART to 8 weeks of TBM treatment in patients with TBM, as fewer adverse events occurred in the delayed treatment group [5].…”

“…Initiation should be as early as possible to support the immune response; however, toxicity, the immune reconstitution syndrome (IRIS) and pill burden may complicate early treatment. Paradoxical TB-IRIS in TB/HIVpatients presents as worsening of symptoms after initial TB treatment response following initiation of ART [98]. Two recent clinical trials on initiation of ART in HIV-associated TB showed that severely immunocompromised (CD4 <200) patients with TB may benefit from early initiation of ART, with lower rates of AIDS-defining illnesses or death, but at the cost of a higher occurrence of IRIS [99,100].…”