Immune reconstitution inflammatory syndrome in HIV-infected patients with mycobacterial infections starting highly active anti-retroviral therapy

Abstract

AIM: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART).

MATERIALS AND METHODS: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared.

RESULTS: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV “viral load”. Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients—severe enough to produce tracheal compression in two patients (one of whom had stridor)—and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion.

CONCLUSION: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started.

Introduction

The incidence and prevalence of both human immunodeficiency virus (HIV) infection and tuberculosis are increasing throughout the world. The incidence of tuberculosis in patients infected with HIV is estimated to be between 50 and 200 times that of the general population,¹ and HIV-infected individuals with latent Mycobacterium tuberculosis infection have a 5–15% yearly risk of developing active tuberculosis.² The incidence of non-tuberculous (“atypical”) mycobacterial infections is also high in untreated patients with advanced HIV infection and low CD4+ T-lymphocyte counts.³

Initiation of highly active antiretroviral therapy (HAART) in HIV-infected individuals has been shown to produce a sustained rise in the CD4+ T-lymphocyte count and partial immune reconstitution,⁴ and is associated with marked improvements in rates of opportunistic infection and mortality.5., 6.

The varied radiological presentations of mycobacterial disease seen in patients with HIV have previously been described; these relate in some degree to the patient's level of immunosuppression.7., 8. A syndrome of transient clinical or radiological deterioration after institution of anti-tuberculous therapy was first described in the general population almost 50 years ago.⁹ This phenomenon is also known as a “paradoxical” response and has been reported in patients with cerebral tuberculosis, nodal disease and advanced pulmonary disease.10., 11., 12., 13., 14. Recently the same phenomenon has been recognized in HIV-infected individuals, in whom worsening of clinically apparent or occult infection after initiation of HAART has been described. Paradoxical responses have been reported in HIV-infected patients being treated for tuberculosis,15., 17. atypical mycobacterial infection¹⁸ and several other opportunistic infections,18., 19. in whom HAART is started. In this population paradoxical responses are also known as immune reconstitution inflammatory syndromes (IRIS). The median onset of IRIS after the initiation of HAART in patients with tuberculosis is 12 days,15., 17. it is usually mild and is frequently self-limiting. We describe here five patients with IRIS associated with mycobacterial infection and unusual features. Three had marked mediastinal lymphadenopathy, with tracheal compression in two patients (in one this was severe and caused stridor). The onset of IRIS was delayed in two patients and occurred 2 months after HAART was started. Biopsy in four patients enabled exclusion of alternative diagnoses and confirmed the diagnosis of IRIS, by demonstration of mycobacteria or abnormal histology.