Opportunistic infections and immune reconstitution inflammatory syndrome in HIV-1-infected adults in the combined antiretroviral therapy era: a comprehensive review

Abstract

Despite the availability of effective combined antiretroviral treatment, many patients still present with advanced HIV infection, often accompanied by an AIDS-defining disease. A subgroup of patients starting antiretroviral treatment under these clinical conditions may experience paradoxical worsening of their disease as a result of an exaggerated immune response towards an active (but also subclinical) infectious agent, despite an appropriate virological and immunological response to the treatment. This clinical condition, known as immune reconstitution inflammatory syndrome, may cause significant morbidity and even mortality if it is not promptly recognized and treated. This review updates current knowledge about the incidence, diagnostic criteria, risk factors, clinical manifestations, and management of opportunistic infections and immune reconstitution inflammatory syndrome in the combined antiretroviral treatment era.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

“…74 Although a randomized clinical trial found no survival benefit of early initiation of ART for HIV-infected persons with active tuberculosis and CD4 cell counts greater than 220/µL, 75 there was no increased harm, and the improved survival observed in the SAPiT, CAMELIA, and STRIDE trials, particularly for those with lower CD4 cell counts, 1,76–78 supports the recommendation to start ART within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/µL or less and within the first 2 to 8 weeks for those with CD4 cell counts above 50/µL (evidence rating AIa). Of note, earlier initiation of ART in persons with active tuberculosis, particularly tuberculosis meningitis, may be associated with higher rates of immune reconstitution inflammatory syndrome and may complicate management of adverse drug reactions, 79 thus mandating careful monitoring in this setting.…”

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

“…In general terms, the expected immune recovery after HAART initiation implies restoration of the CD4 + T cell count, which is characterized by two phases: 1) firstly, recirculation of activated memory T cells that had previously been sequestered in lymphoid tissues (cell redistribution); 2) secondly (4–6 weeks later or longer in patients with advanced disease), increase in the naïve CD4 + T cell counts related to improved thymopoiesis [27–29]. Accordingly, we observed an increase in the percentage of memory CD4 + T cells after 1 month of HAART, in both CNS-IRIS case and controls, but the former showed a higher increase than the latter.…”

Trichosporon: another yeast‐like organism responsible for immune reconstitution inflammatory syndrome in patients with hematological malignancy

“…Immune reconstitution inflammatory syndrome (IRIS), initially reported in the context of AIDS-related opportunistic infections [9], has been described in other settings, notably in neutropenic patients [10]. The rapid relief of an effective immune response, combined with immunomodulatory effects linked to some pathogens' antigens, and to antimicrobials by themselves may lead to severe clinical pictures [9].…”

“…Immune reconstitution inflammatory syndrome (IRIS), initially reported in the context of AIDS-related opportunistic infections [9], has been described in other settings, notably in neutropenic patients [10]. The rapid relief of an effective immune response, combined with immunomodulatory effects linked to some pathogens' antigens, and to antimicrobials by themselves may lead to severe clinical pictures [9]. While mimicking treatment failure, the chronology of the symptoms, the persistently negative cultures and the potential benefit of limiting the immune response, either by delaying the ARV therapy or even adding corticosteroid therapy, support this difficult-to-prove diagnosis [4].…”