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Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy.
Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC, Hamill RJ.
AIDS
2005 Mar 4;19(4):399-406.
Abstract
BACKGROUND: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). OBJECTIVE: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. DESIGN: A retrospective cohort identified through a city-wide prospective surveillance program. METHODS: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. RESULTS: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). CONCLUSIONS: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.
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Reviewed by
Susa Coffey, MD
Comment
The immune reconstitution inflammatory syndrome (IRIS), also known as immune reconstitution disease (IRD), results from an exuberant inflammatory response to particular pathogens in some patients with advanced immunosuppression who have recently initiated antiretroviral therapy (ART). It may present as paradoxical worsening of a partially- or recently-treated infection, or may arise from a previously unrecognized condition. IRIS has been associated with a number of opportunistic infections (OIs), including mycobacterium tuberculosis (TB), Mycobacterium avium complex disease (MAC), cryptococcal disease, cytomegalovirus (CMV) disease, and Pneumocystis jirovecii pneumonia (PCP). It typically is a self-limited phenomenon, but may cause serious complications. While IRIS has been recognized for a number of years, its pathogenesis is not well understood.
This retrospective cohort study, conducted in Houston, examined the incidence of and risk factors for IRIS among HIV-infected patients diagnosed with TB, MAC, or cryptococcus. Patients were included if they received ART and had baseline and follow-up CD4 and HIV RNA studies. 180 patients met the study criteria; their mean CD4 cell count was 31 cells/mm.
Of these, 30% developed IRIS, with no differences in the incidence of IRIS according to the opportunistic infection. The median time between initiation of ART and diagnosis of IRIS was 46 days; IRIS occurred within 90 days in 72% of patients
. Risk factors for the development of IRIS included earlier initiation of ART (relative risk (RR), 2.01 for starting ART within 30 days of starting OI treatment), being ART-naïve, and a larger decrease in HIV RNA in response to ART. The initial CD4 cell count increase was not significantly associated with IRIS.
In the 12 months after starting ART, IRIS patients underwent significantly more invasive procedures and hospitalizations, and two died from complications of IRIS. However, at 24 months, there were no differences in mortality between the IRIS and the non-IRIS groups, and patients who had had IRIS were more likely to have CD4 count increases of >=100 cells/mm over baseline and viral suppression (HIV RNA <400 copies/mL).
The decision of when to start ART in patients with very low CD4 counts and a current or recent OI can be difficult, as clinicians attempt to balance the urgent need for immune reconstitution with the risk of IRIS, as well as the risks of adverse drug effects or interactions from multiple therapies. This study helps to define the risk of IRIS in patients with severe immunosuppression and recently treated or subclinical TB, MAC, or cryptococcal meningitis. However, much more study is needed in order to understand the immune mechanisms involved in IRIS, the risks of IRIS with regard to various pathogens, and the optimal timing of ART in relation to therapy for specific OIs.
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