HIV combination therapy : partial immune restitution unmasking latent cryptococcal infection

• Published in: AIDS (London) Vol. 12; no. 12; pp. 1491 - 1494
• Main Authors: WOODS, M. L, MACGINLEY, R, EISEN, D. P, ALLWORTH, A. M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20.08.1998
• Subjects: AIDS-Related Opportunistic Infections - diagnosis; AIDS-Related Opportunistic Infections - immunology; AIDS-Related Opportunistic Infections - pathology; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Biological and medical sciences; CD4 Lymphocyte Count; Cerebrospinal Fluid - microbiology; Cryptococcosis - diagnosis; Cryptococcosis - immunology; Cryptococcosis - pathology; Cryptococcus; Cryptococcus - isolation & purification; Drug Therapy, Combination; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Medical sciences; Meningitis, Fungal - diagnosis; Meningitis, Fungal - immunology; Meningitis, Fungal - pathology; Retrovirus; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Opportunistic infection; Nervous system diseases; Mycosis; Cryptococcosis; Immune reconstitution; AIDS; Cellular immunity; Immune deficiency; Infection; Chemotherapy; Treatment; Viral disease; Central nervous system disease; Risk factor; Antiviral; Complication; Meningitis; Advanced stage
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199812000-00011

To describe two cases of cryptococcal meningitis and one re-exacerbation of Cryptococcus-associated meningitis occurring in temporal association with commencement of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection (CD4 cells < 50 x 10(6)/l), which suggests that partial immune restitution can facilitate development of clinically apparent meningitis in response to Cryptococcus or its antigen. All HIV-infected patients with culture-proven cryptococcal meningitis diagnosed at a tertiary referral centre specialist infectious diseases unit from 1 January 1996 to 31 December 1996 were reviewed to examine the clinical and immunological parameters prior to and after commencing antiretroviral therapy. Three patients were diagnosed with clinically apparent meningitis within 7-39 days of changing or altering antiretroviral combination therapy consisting of zidovudine or stavudine, in combination with lamivudine and saquinavir. All patients had CD4 cell counts below 50 x 10(6)/l at initiation of therapy. Following institution of HAART, evidence of immune restitution was suggested by the following: (i) significant increases (3.7-14-fold) in numbers of CD4 cells (all three patients), (ii) significantly reduced (> 2-4 log10 reduction) HIV viral loads (two out of three patients), and (iii) prominent inflammatory changes in cerebrospinal fluid (white blood cells > 10 x 10(6)/l) at diagnosis (two out of three patients). Our report suggests that in patients with advanced HIV infection, partial immune restitution induced by HAART can precipitate onset of clinically apparent meningitis in those patients with latent cryptococcal central nervous system infection or with residual cryptococcal antigen present in the cerebrospinal fluid.