HIV COMBINATION THERAPY - PARTIAL IMMUNE RESTITUTION UNMASKING LATENTCRYPTOCOCCAL INFECTION

Objective: To describe two cases of cryptococcal meningitis and one re -exacerbation of Cryptococcus-associated meningitis occurring in tempo ral association with commencement of highly active antiretroviral ther apy (HAART) in patients with advanced HIV infection (CD4 cells < 50 x 10(6)/l), which suggests that partial immune restitution can facilitat e development of clinically apparent meningitis in response to Cryptoc occus or its antigen. Design: All HIV-infected patients with culture-p roven 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 paramete rs prior to and after commencing antiretroviral therapy. Results: Thre e patients were diagnosed with clinically apparent meningitis within 7 -39 days of changing or altering antiretroviral combination therapy co nsisting of zidovudine or stavudine, in combination with lamivudine an d saquinavir. All patients had CD4 cell counts below 50 x 10(6)/l at i nitiation of therapy. Following institution of HAART, evidence of immu ne restitution was suggested by the following: (i) significant increas es (3.7-14-fold) in numbers of CD4 cells (all three patients), (ii) si gnificantly reduced (> 2-4 log,, reduction) HIV viral loads (two out o f three patients), and (iii) prominent inflammatory changes in cerebro spinal fluid (white blood cells > 10 x 10(6)/l) at diagnosis (two out of three patients). Conclusions: Our report suggests that in patients with advanced HIV infection, partial immune restitution induced by HAA RT can precipitate onset of clinically apparent meningitis in those pa tients with latent cryptococcal central nervous system infection or wi th residual cryptococcal antigen present in the cerebrospinal fluid. ( C) 1998 Lippincott-Raven Publishers.