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

Abstract

Background To determine if infectious disease events in HIV‐infected patients treated with highly active antiretroviral therapy (HAART) are a consequence of the restoration of pathogen‐specific 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). Methods Baseline 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. Results Thirty‐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 first 2 months of therapy and when CD4 T‐cell counts were increasing. Mycobacteria‐ and HCV‐related diseases were associated with restoration of pathogen‐specific immune responses. Conclusions We conclude that improved immune function in immunodeficient patients treated with HAART may restore pathogen‐specific immune responses and cause inflammation in tissues infected by those pathogens.