Pathogenesis and prevention of immune reconstitution disease during antiretroviral therapy

Abstract

The risks of unmasking and paradoxical forms of immune reconstitution disease in HIV-infected patients starting antiretroviral therapy (ART) are fuelled by a combination of the late presentation of patients with advanced immunodeficiency, the associated high rates of opportunistic infections (OIs) and the need for rapid initiation of ART to minimize overall mortality risk. We review the risk factors and our current knowledge of the immunopathogenesis of immune reconstitution disease, leading to a discussion of strategies for prevention. Initiation of ART at higher CD4 counts, use of OI-preventive therapies prior to ART eligibility, intensified screening for OIs prior to ART initiation and optimum therapy for OIs are all needed. In addition, use of a range of pharmacological agents with immunosuppressive and immunomodulatory activity is being explored.

Laryngeal Kaposi's Sarcoma Complicated by the Immune Reconstitution Inflammatory Syndrome in an HIV-infected Patient

“…The ART-induced KSHV-specific inflammatory response might result in an increase in an-gioproliferative and tumorigenic factors (14), which may contribute to further exacerbation of KSHV (15). Systemic chemotherapy is likely to have a positive impact on KS itself, as well as attenuating reconstituted immune responses by preventing these reactions.…”

Immune Reconstitution Inflammatory Syndrome

“…5 Early initiation of HAART during treatment for an opportunistic infection, high antigen load in those with advanced opportunistic infection, low baseline CD4 cell counts, high baseline viral load, and marked immunological and virological responses to HAART are the well-established risk factors for paradoxical IRIS. 6 Development of unmasking and paradoxical IRIS can be prevented by decreasing the risk of an opportunistic infection through early diagnosis of HIV infection and initiation of HAART when the CD4 cell counts are Ͼ 200 cells/L. 6 Furthermore, the risk of paradoxical IRIS could be reduced by delaying the timing of HAART during treatment for certain opportunistic infections such as pulmonary tuberculosis.…”

“…6 Development of unmasking and paradoxical IRIS can be prevented by decreasing the risk of an opportunistic infection through early diagnosis of HIV infection and initiation of HAART when the CD4 cell counts are Ͼ 200 cells/L. 6 Furthermore, the risk of paradoxical IRIS could be reduced by delaying the timing of HAART during treatment for certain opportunistic infections such as pulmonary tuberculosis. 5 However, several randomized controlled trials indicate that early initiation of HAART has an overall benefit on the survival of patients.…”

Neues bei HIV und Neuro-Aids

“…Bei der Behandlung opportunistischer Infektionen des ZNS ist das Risiko in Korrelation zum Immunstatus, ein IRIS zu entwickeln, zu berücksichtigen. Dieses Risiko scheint für die opportunistischen Infektionen des ZNS unterschiedlich zu sein [63].…”