Prednisolone Ineffective Against HIV-Associated Pleural Tuberculosis

ALEXANDRIA, VA. -- Prednisolone, a glucocorticoid that is sometimes added to anti-tuberculosis drug regimens, should not be used to treat patients with pleural tuberculosis and HIV infection, nor can it be recommended for those with pleural tuberculosis who are not co-infected with HIV, according to a study in the August 15, 2004 issue of The Journal of Infectious Diseases.

 Alison M. Elliott, of the London School of Hygiene and Tropical Medicine, and colleagues from Uganda, England, and the United States conducted a double-blind, placebo-controlled study of prednisolone in 197 patients with HIV-1-associated pleural tuberculosis. The expectation was that the drug might retard HIV progression and thus prolong survival. In fact, it had no effect on survival but did increase the risk of the AIDS-related cancer Kaposi's sarcoma.

The investigators noted that, although prednisolone suppresses the immune system's response to tuberculosis when used alone, its use is associated with improved survival when taken with anti-tuberculosis drugs­­-notably, in pericardial tuberculosis. Previous studies had shown that active tuberculosis is associated with a high degree of immune activation, which also plays a large role in promoting HIV replication. The investigators therefore hypothesized that adding prednisolone to a regimen of anti-tuberculosis drugs might inhibit viral replication, retard progression of HIV disease, and improve long-term survival. As prednisolone is relatively inexpensive and widely available, this would have been of value in fighting tuberculosis and HIV co-infection, especially in resource-poor regions of the world as sub-Saharan Africa.

The authors performed their study at the National Tuberculosis Treatment Centre in Kampala, Uganda between November 1998 and January 2002. Of the 197 patients  studied, 99 were given prednisolone and 98 a placebo, along with standard tuberculosis treatment.

 The patients receiving prednisolone did see improvement in the principal signs and symptoms of pleural tuberculosis, especially anorexia, weight loss, and cough. Although prednisolone use was not associated with such HIV-associated opportunistic diseases as cryptococcal meningitis, esophageal or oral candidiasis, herpes zoster, or oral or genital herpes simplex infection, it did significantly increase the risk of Kaposi's sarcoma, six cases of which were observed, and only in the prednisolone group. This finding mirrored a previous Zambian study in which Kaposi's sarcoma also occurred only in a group given prednisolone to treat pleural tuberculosis.  An opportunistic disease associated with human herpes virus 8 infection, Kaposi's sarcoma is often difficult to treat and may be fatal.

Given an increased risk of Kaposi's sarcoma, no improvement in survival, and no reported long-term benefits of glucocorticoids in patients with pleural tuberculosis who were not HIV-infected, the authors concluded that pleural tuberculosis should not be treated with prednisolone, regardless of HIV status. This recommendation, they noted, does not extend to other uses of prednisolone, such as treatment of pericardial tuberculosis or Pneumocystis carinii pneumonia, for which the drug can prolong or save lives, regardless of a patient's HIV status. They warned, however, that "prednisolone should be used with caution in situations where no beneficial effect on immediate survival can be expected."

Source: Infectious Diseases Society of America (IDSA)