Use of Prednisolone in HIV-associated Tuberculous Pleurisy Is Not Recommended

Active tuberculosis may accelerate progression of HIV-1 infection by promoting viral replication in activated lymphocytes. Glucocorticoids are used in pleural * tuberculosis to reduce inflammation-induced pathology, and their use also might reduce progression of HIV by suppressing immune activation. Researchers examined the effect that prednisolone has on survival in HIV-1–associated pleural tuberculosis.

The investigators conducted a randomized, double-blind, placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment, in adults with HIV-1–associated pleural tuberculosis. The primary outcome was death. Analysis was by intention to treat.

Results    

Of 197 participants, 99 were assigned to the prednisolone group and 98 to the placebo group. The mortality rate was 21 deaths/100 person-years (pyr) in the prednisolone group and 25 deaths/100 pyr in the placebo group (age-, sex-, and initial CD4+ T cell count–adjusted mortality rate ratio, 0.99 [95% confidence interval, 0.62–1.56] [P = .95]).

Resolution of tuberculosis was faster in the prednisolone group, but recurrence rates were slightly (though not significantly) higher, and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma (4.2 cases/100 pyr, compared with 0 cases/100 pyr [P = .02]).

Conclusions    

The authors conclude, “In view of the lack of survival benefit and the increased risk of Kaposi sarcoma, the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended.”

Discussion

The results of this study show that the use of prednisolone as an adjunct to treatment for tuberculosis did not improve survival in the HIV-1–infected adults with pleural tuberculosis who participated in the study.

There was a marked and sustained increase in CD4+ T cell counts following treatment for tuberculosis, but, paradoxically, this was accompanied by an increase in viral load, suggesting that the increase in CD4+ T cell counts may not have been associated with an improvement in the immune response against HIV infection. A similar increase in CD4+ T cell counts occurred in both the prednisolone and placebo groups, which is in keeping with prednisolone's lack of effect on mortality.

“Of great concern,” write the authors, “was the striking association observed between the use of prednisolone and the incidence of Kaposi sarcoma.” There have been a considerable number of reports of Kaposi sarcoma occurring in patients not infected with HIV following the use of immunosuppressive drugs -particularly of glucocorticoids - after transplantation, in treatment of autoimmune diseases, and in tuberculous pericarditis.

The mechanisms by which prednisolone promotes the development of Kaposi sarcoma remain to be determined.

Kaposi sarcoma is a disease that causes prolonged suffering, is difficult and expensive to treat, and is usually fatal. The investigators  therefore conclude,

“In view of the lack of survival benefit and the significant increase in incidence of Kaposi sarcoma, prednisolone should not be used in the treatment of pleural tuberculosis. This recommendation can be applied regardless of HIV status, because no long-term benefits have been reported with regards to the use of glucocorticoids in patients with pleural tuberculosis who are not infected with HIV.”

They continue, “This recommendation cannot necessarily be generalized to apply to the use of prednisolone for other forms of tuberculosis or for other indications in HIV-infected patients. In the case of pericardial tuberculosis, the use of prednisolone has been shown to improve survival regardless of HIV status, and its use should be continued.”

“Similarly, the use of prednisolone is lifesaving, and should continue, in severe Pneumocystis carinii pneumonia (PCP); however, in HIV-infected patients, prednisolone should be used with caution for indications where no beneficial effect on immediate survival can be expected.”

*Pleurisy: inflammation of the pleura, the membrane that envelops the lungs and the lining the walls of the pleural cavity.

Uganda Virus Research Institute, Entebbe, and Uganda–Case Western Reserve University Research Collaboration, Mulago Hospital, Kampala, Uganda; London School of Hygiene and Tropical Medicine, London, United Kingdom; University of Medicine and Dentistry of New Jersey, Newark.

08/16/04

Reference
A M Elliott and others. A Randomized, Double-Blind, Placebo-Controlled Trial of the Use of Prednisolone as an Adjunct to Treatment in HIV-1-Associated Pleural Tuberculosis. The Journal of Infectious Diseases 190(5): 869-878. September 1, 2004.