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AIDS 2004; Bangkok, Thailand; July 11-16, 2004

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UNBP0870 11/14

The Body PRO Covers: The XV International AIDS Conference

Treatment of HIV Infection With Prednisolone

July 13, 2004

Background

This was one of the most surprising studies presented at this conference. The concept of using prednisolone, a corticosteroid, in HIV treatment runs directly opposite to conventional wisdom. It is well known that chronic corticosteroid use leads to immune suppression; this would seem to be the last thing that someone with HIV would need. Thus, most clinicians use these agents with fear and trepidation in HIV-infected patients.

Previous studies have shown, however, that short-course corticosteroids may be used safely in HIV-infected patients with minimal impact on HIV-RNA levels.1 This current study goes one better and suggests that the chronic use of low-dose corticosteroids may actually lead to clinical benefit for HIV-infected patients.

But how can immunosuppressive therapy be a good thing in HIV infection, when the virus itself causes immune damage? One explanation is that dampening the generalized immune response may reduce the potential for activation of latently infected CD4+ cells in response to antigenic stimulation. Another possible mechanism is a "predator-prey" effect, in which minimizing CD4+ cell proliferation will result in less "prey" available for the HIV "predator."

Another study, published in 1995, tested the use of corticosteroids for HIV infection.2 This trial looked at relatively high-dose prednisolone (0.5 mg/kg/day) in 44 subjects with asymptomatic HIV infection. After 1 year of treatment, the mean CD4+ cell count went from 438 to 557 cells/mm3. An interesting study, but concern about side effects from the high dose of prednisolone probably curtailed interest in follow-up studies. In addition, 1995 was the dawn of the HAART era, and researchers probably decided they had bigger fish to fry. This study revisits the use of corticosteroids for HIV infection, but with a much lower dose that would be more suitable for chronic therapy.

The Prednisolone Study

The presenting author of this report, Dr. Albrecht Ulmer, came up with the idea of using prednisolone for treatment of HIV infection through some anecdotal observations. In 1991, he observed a significant jump in CD4+ cell count in an HIV-infected patient on prednisolone for chronic bronchitis. After a similar CD4+ cell increase in another patient, Ulmer began to use low-dose prednisolone in treatment-naive patients, as well as in conjunction with structured treatment interruption (STI). This retrospective study provides details on his experience with prednisolone over the last several years.

The dose of prednisolone used was typically 5 mg daily, although some patients were treated with 7.5 mg. The study looked at 56 treatment-naive patients with a CD4+ cell count >300 cells/mm3 (mean 567 cells/mm3) who received prednisolone for 0.5 to 11 years. These patients were compared to a group of 132 untreated HIV-infected patients in Ulmer's practice.

The results were quite interesting. Untreated patients followed the expected course, with a decline in CD4+ cell count of about 200 cells/mm3 over 3 years. In contrast, patients receiving prednisolone had a stable CD4+ cell count over the same period. There were statistical differences reported between the groups, but they are difficult to interpret because of the drop-off in numbers of patients with 3-year follow-up (12 remaining in the prednisolone group and 33 in the control group). The CD4:CD8 ratio and CD4+ cell percentage correlated closely with the absolute CD4+ cell count in both groups.

There were no significant differences between the groups in terms of HIV-RNA levels, although there was a trend toward lower viral loads in the prednisolone group. When patients on prednisolone were stratified on the basis of viral load, CD4+ cell counts were more stable in those with HIV-RNA levels <30,000 copies/mL.

The use of prednisolone was also looked at in the context of STI. Patients who were treated during the first 6 months were compared to those who simply had an STI. There were 86 patients in the prednisolone group and 41 in the control group. The slope of CD4+ cell count decline was significantly lower in the prednisolone group than in the untreated control group (0.47 vs. 0.77 cells/mm3/day). Another 30 patients had prednisolone added more than 1 year after STI, which led to a change in the slope of CD4+ cell decline from 0.59 to 0.11 cells/mm3/year.

Commentary

The conclusion of the authors was that it seemed possible to achieve a notable prolongation of time without HAART by means of low-dose glucocorticoid therapy. Based on their retrospective clinical experience, they may be right. If they are correct, there would be potentially far-reaching effects on HIV management. Clearly, though, the answer to this important question will depend upon the results of prospective randomized studies. It will also be important to perform follow-up studies using low-dose corticosteroids for both treatment-naive patients and those undergoing STI.

However, because corticosteroids are inexpensive generics without major profit potential, these studies will not be undertaken by the antiretroviral drug industry. Rather, it will be up to academic researchers and government-funded research consortia to follow this lead and determine whether corticosteroids will have a future role in the management of HIV infection.

Footnotes

  1. McComsey GA, Whalen CC, Mawhorter SD, et al. Placebo-controlled trial of prednisone in advanced HIV-1 infection. AIDS. February 16, 2001;15(3):321-327.

  2. Andrieu JM, Lu W, Levy R. Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. J Infect Dis. March 1995;171(3):523-530.

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Reference

Abstract: Better CD4-Counts With Prednisolone (Poster TuPeB4582)
Authored by: A Ulmer, M Mueller, B Frietsch


This article was provided by TheBodyPRO.com. It is a part of the publication The XV International AIDS Conference.
 



Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.
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