Update on immune reconstitution inflammatory syndrome: progress and unanswered questions.
ABSTRACT The immune reconstitution inflammatory syndrome (IRIS) is characterized by clinical deterioration occurring after the initiation of effective antiretroviral therapy (ART) and results from a disordered and exuberant immune response. The syndrome may present as paradoxical IRIS or unmasking IRIS, depending on whether an opportunistic infection was recognized and treated before ART initiation. Numerous descriptions of IRIS caused by many pathogens were published in the years after the introduction of effective ART. In recent years, with enhanced rollout of ART in resource-limited settings, attention has again focused on IRIS because of the enormous burden of opportunistic infections. This review highlights recent findings elucidating risk factors for and the pathogenesis and treatment of IRIS.
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ABSTRACT: Tuberculous meningitis (TBM) is a preventable and curable common health problem among African adults. Poor nutrition, poverty, household crowding, drug resistant tuberculosis (TB) strains, AIDS, and malfunctioning TB control programs are important risk factors. We conducted a systematic review and meta-analysis of published literature reporting case-fatalities of TBM among adults in African countries from 1970 till date. A PubMed search identified relevant papers. Employed terms include 'adult tuberculous meningitis' AND 'tuberculosis Africa'. PRISMA review guidelines were applied. Adult TBM case-fatalities, odds ratio (OR), relative risk (RR), forest-plot meta-analysis for weighted OR and RR, funnel plots, L'Abbé plots, meta-regressed bubble plots, and inter-study homogeneity were computed. Among 15 studies included, adult TBM occurred in up to 28 % of all meningitis forms with case-fatality of 60 % (inverse-variance weighted 54 %). Fixed-effect meta-analysis revealed weighted OR and RR of adult TBM fatalities to be 4.37 (95 % CI 3.92, 4.88) and 2.53 (95 % CI 2.38, 2.69), respectively. Inter-study homogeneity was reliable, regional representativeness was adequate allowing generalizability, and funnel-plots behaved symmetrically with insignificant inconsistency. All cases were initiated with anti-TB medication, while some had 'breakthrough' TBM. In Africa, adult TBM has a significant public health importance with a very high fatality which has remained stagnant for the past half-century. This reflects ongoing low quality of medical care at facilities where lengthy referrals end up. Community-based studies can reveal higher unaccounted morbidity, accrued disability, and larger mortality. Improving access points for early TB management at community-level, developing health infra-structure for comprehensive case management at facility-level, and poverty reduction can help combat this multi-faceted problem-whose reduction can in return help fight poverty.Journal of Neurology 08/2013; 261(5). DOI:10.1007/s00415-013-7060-6 · 3.84 Impact Factor
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ABSTRACT: To analyze cases of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the CAMbodian Early versus Late Introduction of Antiretrovirals (CAMELIA) randomized trial designed to compare early (2 weeks) versus late (8 weeks) antiretroviral therapy (ART) initiation after tuberculosis treatment onset in Cambodia (NCT00226434). ART-naive adults with CD4 cell count of 200 cells/μl or less, newly diagnosed tuberculosis, and at least one follow-up visit after ART initiation were included in this analysis. Each case of suspected TB-IRIS was systematically validated by two physicians not involved in patients' management. Factors associated with occurrence of TB-IRIS were identified using the Cox proportional hazard model. Among 597 patients, 26% experienced TB-IRIS with an incidence rate of 37.9 cases per 100 person-years [95% confidence interval (CI) 32.4-44.4]. Main clinical manifestations included new or worsening lymphadenopathy (77.4%) and fever (68.4%). Chest radiograph revealed new or worsening abnormalities in 53.4%. Symptoms resolved in 95.5% of patients. Six deaths were directly related to TB-IRIS. Initiating ART early increased the risk of TB-IRIS by 2.61 (95% CI 1.84-3.70). Extrapulmonary or disseminated tuberculosis, CD4 cell count of 100 cells/μl or less, and HIV RNA concentration more than 6 log10 copies/ml were also significantly associated with higher risk of TB-IRIS. Shortening the delay between tuberculosis treatment onset and ART initiation to 2 weeks was associated with an increased risk of developing TB-IRIS. However, TB-IRIS was generally easily manageable. Given the marked reported survival advantage of early ART initiation after tuberculosis treatment onset, these data indicate that fear of TB-IRIS should not be an impediment to early ART in adults with advanced immunodeficiency in resource-limited, high burden settings.AIDS (London, England) 10/2013; 27(16):2577-2586. DOI:10.1097/01.aids.0000432456.14099.c7 · 6.56 Impact Factor
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ABSTRACT: The immune reconstitution inflammatory syndrome (IRIS) is a well-described phenomenon in HIV-infected patients following initiation of antiretroviral therapy and can lead to significant morbidity and mortality in some patients. Risk for IRIS is enhanced in those with low CD4 counts and preexisting opportunistic infections. The development of pathogen-specific definitions of IRIS has aided classification of patients and has facilitated research. Newer data on optimal timing of ART initiation, with additional data in the setting of tuberculosis and cryptococcal meningitis, will help guide strategies to decrease the risk of IRIS but must balance the risks of HIV disease progression. Managing patients with IRIS can be challenging. Treatment options include pathogen-specific therapy, antiinflammatory therapies, and other novel approaches.Current Infectious Disease Reports 12/2012; 15(1). DOI:10.1007/s11908-012-0308-y