Immune restoration disease after the treatment of immunodeficient HIV‐infected patients with highly active antiretroviral therapy

Abstract

BackgroundTo determine if infectious disease events in HIV-infected patients treated with highly active antiretroviral therapy (HAART) are a consequence of the restoration of pathogen-speci®c immune responses, a single-centre retrospective study of all HIV-infected patients commencing HAART prior to 1 July 1997 was undertaken to determine the incidence, characteristics and time of onset of disease episodes in HAART responders (decrease in plasma HIV RNA of > 1 log 10 copies/mL). MethodsBaseline and post-therapy changes in CD4 T-cell counts and HIV RNA were compared in patients with and without disease and delayed-type hypersensitivity responses to mycobacterial antigens were measured in selected patients. ResultsThirty-three of 132 HAART responders (25%) exhibited one or more disease episodes after HAART, related to a pre-existent or subclinical infection by an opportunistic pathogen. Disease episodes were most often related to infections by mycobacteria or herpesviruses but hepatitis C virus (HCV), molluscum contagiosum virus and human papilloma virus were also implicated. They were most common in patients with a baseline CD4 T-cell count of < 50/uL and occurred most often during the ®rst 2 months of therapy and when CD4 T-cell counts were increasing. Mycobacteria-and HCV-related diseases were associated with restoration of pathogen-speci®c immune responses. ConclusionsWe conclude that improved immune function in immunode®cient patients treated with HAART may restore pathogen-speci®c immune responses and cause in¯ammation in tissues infected by those pathogens. Key words: HAART, HIV, immune restorationReceived: 4 June 1999, accepted 13 September 1999 IntroductionWhile the immediate aim of using antiretroviral therapy is suppression of HIV replication, the ultimate aim is restoration or maintenance of protective HIV-speci®c and pathogen-speci®c immune responses. Treatment of immunode®cient patients with highly active antiretroviral therapy (HAART) appears to restore pathogen-speci®c immune responses resulting in prevention or regression of diseases caused by opportunistic pathogens [1]. However, in some patients suppression of HIV replication by antiretroviral therapy and the resultant increase in blood CD4 T-cells is associated with in¯ammation in tissues infected by those pathogens. Thus, disease related to subclinical or pre-existent infections by Mycobacterium avium complex (MAC) [2±4], M. tuberculosis (MTB) [5,6], Bacille Calmette±Guerin (BCG) [7], cytomegalovirus (CMV) [8±10], hepatitis B virus (HBV) [11,12], hepatitis C virus (HCV) [13] immunological response to HAART. Many of these disease episodes were associated with the presence of a pathogenspeci®c immune response and/or more exaggerated inammatory response than is usually present in patients with opportunistic infections. It has therefore been argued that the disease results from the effects of a restored immune response against the pathogen [2±7,10,11,13,14]. However, Michelet et al. have argued that`opportunistic infections' in patients treated...

HIV-related lung disorders

“…This definition addresses two important points: 1) it correctly excludes toxicities of the individual drugs used and 2) it implicates immune recovery rather than residual defects in cell-mediated immunity as responsible for IRIS. When applying this definition, it is estimated that between 10% and 25% of patients who begin HAART will experience IRIS of varying intensity and severity [43].…”

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“…Cela pour au moins trois raisons: d'abord, la spécificité de la morbidité liée au VIH en Afrique peut entraîner une fréquence de morbidité sous antiré-troviraux différente de ce qui est connu en France, pouvant avoir un retentissement d'autant plus important sur la conduite du traitement que les moyens diagnostiques et le niveau de prise en charge sont différents. Par exemple, l'ampleur du problème des réactivations mycobactériennes pourrait prendre une importance qu'elle n'a pas lorsque le plateau technique permet un diagnostic rapide et bien documenté [57,58]. Ensuite, les effets secondaires (types et fréquence) et leur retentissement (qui, à même fréquence, peut être différent du retentissement qu'ils ont en France du fait du niveau de prise en charge) sont susceptibles de conditionner la réussite d'une stratégie théra-peutique [59].…”

Clinical Outcomes of Use of Hydroxychloroquine in Paradoxical Tuberculosis-Immune Reconstitution Inflammatory Syndrome in Hiv-Infected Patients.

“…Mycobacterial and fungal forms of IRIS usually present with features of T-helper 1 immune response, manifesting with granulomatous inflammation, or suppuration. In contrast, CD8+ T-cells are the dominant inflammatory cells found in IRIS related to viruses [4,5].…”