AEGiS-GMHC: Immunosuppressive Therapy for HIV Infection

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Immunosuppressive Therapy for HIV Infection

Gay Men's Health Crisis: Treatment Issues, Volume 8 no. 9 - October 1994
Craig Sterritt

Researchers have long tried to reconcile the fact that while the activation of CD4 cells is required for effective anti-HIV immune responses, it also leads to increased HIV replication and the susceptibility of uninfected CD4 cells to HIV infection. In addition to facilitating the viral life-cycle, activation of CD4 cells from people with HIV has been found to lead to a phenomenon called programmed cell death or apoptosis, which is thought to contribute to the overall loss of CD4 cells in HIV infection. The overactivation of CD4 cells in HIV can also lead to other deleterious events, including aberrant cytokine secretion, the overproduction of antibodies and chronic inflammation, all of which may also be involved in the development of HIV-related disease.

Supporting a correlation between CD4 hyperactivation and CD4 depletion was a presentation at the recent International AIDS Conference that described a French study[1] of prednisolone, a gluccocorticoid with anti-inflammatory and immunosuppressive effects. The French group administered prednisolone to 243 asymptomatic and twenty mildly symptomatic persons with HIV in this non-placebo-controlled trial. Investigators reported that they observed a peak gain of over 200 CD4 cells per mm3 of blood after fifteen days of therapy. One year later, trial members still were a median of 100 CD4 cells above their baseline counts. HIV p24 antigen as well as viral DNA, RNA and mRNA remained stable in all patients over the course of the trial, indicating that prednisolone treatment does not promote HIV replication. Obviously, too, the increase in CD4 counts was not caused by reduced virus levels.

Immune system and CD4 cell activation markers in the prednisolone recipients decreased significantly, although cytotoxic lymphocyte (CD8 cell) counts remained unchanged. In addition, swollen lymph nodes (lymphadenopathy) disappeared in sixteen of the twenty mildly symptomatic patients, indicating reduced lymph node activity. No major side effects or opportunistic infections occurred during the course of the study.

In vitro (test tube) tests done in conjunction with the trial revealed that prednisolone exerts its positive influence on CD4 counts by preventing apoptosis. Prednisolone was not found to inhibit normal functioning of cells: Cells treated with prednisolone could still produce the cytokine interleukin-2 and proliferate following exposure to antigen (such as HIV protein).

1 Andrieu JM et al. Tenth International conference on AIDS abstract book. Aug 7-12, 1994; 1(abstract 157B):46.

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