Unexpected reactions following highly active anti‐retroviral therapy in patients with HIV‐1 infection and tuberculosis

Abstract

Purpose:Highly active anti‐retroviral therapy (HAART) dramatically improves the prognosis of AIDS patients. However, some patients with opportunistic infections suffer from the hyperreactive inflammation (HRI) following HAART, which sometimes interferes with the continuation of HAART. In order to clarify the mechanism of HRI, we investigated the clinical course of these cases and performed in vitro and in vivo analyses.Materials and methods:AIDS patients with active opportunistic infections including miliary tuberculosis, Mycobacterium avium complex (MAC) bacteraemia, Pneumocystis carinii pneumonia (PCP), disseminated cryptococcosis were included in the present study. We started HAART after treatment of these opportunistic infections. Blood and clinical samples were obtained from infective sites to make the definitive diagnosis and to prove HRI. Peripheral blood mononuclear cells (PBMC) obtained and stored sequentially during lymphadenitis due to Mycobacterium tuberculosis were stimulated with purified protein derivative (PPD) in vitro and measured lymphocyte proliferation and cytokine production.Results and conclusions:Hyperreactive inflammation occurred 3 weeks on average after starting HAART in most patients who had these opportunistic infections. Discrimination between HRI and deterioration of the infection was sometimes very difficult. If we were able diagnose HRI, we treated the patients with corticosteroid to mitigate HRI. Two‐thirds of the patients continued HAART, but the remaining cases had to have HAART suspended due to severe reactions including fever (> 40°C) and pain of lymphadenitis. In vitro study with the PPD stimulation revealed that proliferating lymphocytes existed in peripheral blood and γ‐interferon was produced from such PBMC. These results might support the fact that the infective site must have the much stronger reaction to the opportunistic pathogen. If it was true, use of steroids makes sense to control the reaction. Actually, treatment with the steroid to HRI is successful. However, how to use the steroid (e.g. how much dose and how long) is to be elucidated from future clinical observations.Acknowledgements:The following doctors are acknowledged for their contribution to this study: M. Tanaka, C. Yasuoka, Y. Takahashi, S. Ida, N. Tachikawa, Y. Kikuchi, A. Yasuoka, and Y. Hirabayashi. This study was supported by a grant for AIDS Research from the Ministry of Health and Welfare of Japan.