Abstract
BackgroundTo test the hypothesis of down-regulating the increased immune system activation/destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. We thus designed in 1992 a pilot study to evaluate the clinical, immunologic and virologic effects of PDN. The drug was given to a group of 44 patients with CD4 T cells over 200/μl. After one year, no patient had developed clinical AIDS and the mean CD4 T cell count of the group had increased from 441 ± 21 cells/μl to 553 ± 43 cells/μl. Moreover, markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged. Here we explore the long-term clinical, immunologic, and virologic impact of prednisolone on the chronic phase of HIV infection.MethodsRetrospective study over 10 years starting between July 1992 and February 1993. A total of 44 patients with CD4 cells/μl ranging from 207 to 775 were treated with prednisolone, 0.5 mg/kg/d, over 6 months and 0.3 mg/kg/d thereafter.ResultsNo clinical AIDS developed under prednisolone; side effects of the drug were mild. CD4 cells which increased from 421 cells/μl at entry to 625 cells/μl at day 15, slowly decreased to reach 426 cells/μl after two years; T cell apoptosis and activation markers dropped within 15 days to normal levels and reincreased slowly thereafter. Serum viral loads remained stable. The percentage of patients maintaining CD4 cells over entry was 43.2% at two years, 11.4% at five years and 4.6% at 10 years. Initial viral load was highly predictive of the rate of CD4 decrease under prednisolone.ConclusionsPrednisolone postponed CD4 cell decrease in a viral load dependent manner for a median of two years and for up to 10 years in a fraction of the patients with a low viral load. These findings might stimulate clinical trials as well as biological research on the role of antiapoptotic drugs in HIV infection.
Highlights
To test the hypothesis of down-regulating the increased immune system activation/ destruction process associated with chronic human immunodeficiency virus type 1 (HIV) infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication
After three to 20 years of CD4 T cell depletion and immune activation, which are generally clinically asymptomatic, the CD4 T cell pool eventually collapses and the various clinical manifestations of AIDS develop. These observations led us to be interested in immunosuppressive compounds as potential treatments of the chronic phase of HIV infection and tools to better understand its pathogenesis [1]
Long-term follow-up of these patients showed that their mean CD4 cell count remained stable under Cyclosporin A (CSA) while it decreased after CSA withdrawal [3]
Summary
To test the hypothesis of down-regulating the increased immune system activation/ destruction process associated with chronic HIV infection, we focused our interest on prednisolone (PDN), because we had showed that, in vitro, PDN had a strong anti-apoptotic activity on activated T cells of HIV-infected patients and no effect on viral replication. After three to 20 years of CD4 T cell depletion and immune activation, which are generally clinically asymptomatic, the CD4 T cell pool eventually collapses and the various clinical manifestations of AIDS develop These observations (most of which were available in the middle of the 1980s) led us to be interested in immunosuppressive compounds as potential treatments of the chronic phase of HIV infection and tools to better understand its pathogenesis [1]. Markers of immune activation had dropped back to normal levels while the mean viral load of the group had remained unchanged [5] At completion of this one-year study, patients were offered to remain under PDN for a second year. We present the 10-year results of this retrospective study
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