Early ReportFocal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease
Introduction
The HIV-1 protease, a 99-aminoacid aspartyl protease homodimer, is esssential for the production of infectious HIV virions by the processing of gag and gag-pol polypeptide precursors.1, 2, 3, 4, 5, 6, 7, 8 In vitro, inhibitors of HIV protease are effective against both HIV-1 and HIV-2 strains.9 At present, three HIV-1 protease inhibitors are in widespread clinical use—saquinavir (Invirase, Roche), ritonavir (Norvir, Abbott), and indinavir (Crixivan, Merck). These agents produce a rapid decrease in plasma HIV-RNA of 10-100-fold or greater, with concomitant increases in CD4-lymphocyte counts, in some cases, of more than 100 cells/μL.10, 11, 12, 13, 14, 15, 16 Although these new antiretroviral therapies hold great promise in the treatment of HIV-1 infection, they are associated with significant drug interactions and cause several adverse effects. We report a distinct clinical syndrome in patients with advanced HIV-1 disease that followed administration of indinavir.
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Patients and methods
Between April and December, 1996, five HIV-1-infected patients were identified after admission to the Beth Israel Deaconess Medical Center (Boston, MA, USA) for assessment of fever, leucocytosis, and lymph-node enlargement within 1–3 weeks of starting indinavir therapy. All patients gave informed consent for the studies described below. All patients had baseline (before indinavir) CD4 T-helper lymphocyte counts of less than 50 cells/μL. Routine blood-isolator cultures for mycobacteria and fungi
Results
Clinical and laboratory data of the five patients admitted with fever, leucocytosis, and focal inflammatory lymphadenitis after starting indinavir therapy are shown in the table.
Discussion
We have described a distinct clinical syndrome associated with the initiation of a protease inhibitor, indinavir sulphate, in patients with advanced HIV-1 disease. Each of the five patients in this series was clinically stable and afebrile before indinavir therapy. However, after receiving the protease inhibitor, all five patients required admission to hospital for severe, febrile syndromes of long duration, which were attributable to a previously subclinical MAC infection.
This inflammatory
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