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Conference
"Opportunistic Infections" Dr. Peter Phillips (biography) English - 2003-03-30 - 37 minutes
Summary : Immune Reconstitution Disease (IRD). Since the availability of highly active antiretroviral therapy, an increasing number of opportunistic pathogens have been associated with a wide range of IRDs. The severity ranges from life threatening inflammatory reactions (e.g progressive multifocal leukoencephalopathy, pCP, cryptococcal meningitis) to more benign conditions such as herpes zoster infection. Other HIV-associated conditions which have been described in the context of IRD include tuberculosis, MAC, CMV, hepatitis B and C and histoplasmosis. Occasionally non-infectious autoimmune diseases may also be exacerbated by HAART-induced immune reconstitution, including Graves’ disease, autoimmune thyroiditis, and SLE. Occasional IRD syndromes have also been described in patients with lymphoma, Kaposi’s sarcome, Castleman’s disease and sarcoid-like disorders.
A definitive diagnosis may be possible in some cases, but only suspected in others. For example, in tuberculous IRD, the TB diagnosis typically preceded the initiation of antiretrovirals, and the diagnosis of MTb-IRD is one of exclusion. In contrast, for MAC-Related IRD, the HAART regimen usually unmasks subclinical MAC and a definitive diagnosis can be established by isolating the organism from a normally sterile site. The diagnosis of HIV-related IRD generally rests upon the following: a) the finding of a localized inflammatory process; and b) smear or culture positive for the opportunistic pathogen; and c) evidence of immune reconstitution (increase in CD4 cell count and often a shift toward a histologic tissue reaction more consistent with intact cell mediated immunity, e.g. necrotizing granulomas in mycobacterial infection). Clinical featured of the IRDs are often atypical compared to the classic description of the infections in the pre-HAART era. Althought the majority of these problems deelop witin the first few months of initiating (or revising) an antiretroviral regimen, such reactions have been well described up to a year or more following the initiation of HAART.
Mild IRDmay not require any therapy. Most patients are treated with antimicrobials specific for the responsible pathogen, however the efficacy of such therapies in these settings has not been established. Anecdotal reports suggest a role a systemic corticosteroids in those patients with more severe or persistent inflammatory reactions. Antiretroviral therapy should not be interrupted unless the IRD episode is considered to be life-threatening. Effective prevention strategies for IRS have not been determined. Azithromycin prophylaxis does not appear to prevent MAC-IRD. In order to minimize uncertainty regarding the cause of fevers or inflammatory reactions, it has been recommended that HAART therapy be postponed for 1 to 2 months after the initiation of antituberculous therapy in patients with newly diagnosed TB. A similar recommendation may apply to other opportunistic diseases. The natural course of MAC-IRD included the gradual resolution of symptoms and signs over weeks or months as observed in a small number of patients who have declined specific antimicrobial therapy. IRS should be considered in the differential diagnosis of problems developing within a year or more of initiating or revising HAART.
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