Placebo-controlled trial of prednisone in advanced HIV-1 infection

Objective: To examine the safety and the immunologic and virologic conseque nces of corticosteroid use in HIV-1 infection. Methods: A randomized, double-blinded, placebo-controlled trial of corticos teroid administration in 41 patients with advanced HIV-1 infection. Patient s had a baseline median CD4 cell count of 131 x 10(6) cells/l at enrollment and 85% had a history of opportunistic infection. All but one of the patie nts had been taking stable antiretroviral regimen, including a protease inh ibitor in 36, for a median duration of 158 days. Patients were randomized t o 8 weeks of prednisone 0.5 mg/kg daily or placebo. Results: No AIDS-defining events occurred; two patients in each group devel oped oral candidiasis, and two patients on prednisone developed mild herpes simplex flares. None who developed oral candidiasis or herpes simplex was receiving prophylaxis and each responded promptly to therapy. In the predni sone group, two patients developed hyperglycemia and one diabetic increased insulin requirements. CD4 cell counts and plasma HIV-1 RNA levels did not change, but plasma tumor necrosis factor alpha levels and CD38+CD8+ cells d ecreased significantly in those taking prednisone. Conclusion: Short-term prednisone administration is well tolerated and reas onably safe in advanced HIV-1 disease and decreases immune activation witho ut effects on HIV-1 RNA levels or CD4 cell counts. These results suggest th at, in stable HIV-1 disease, these immune activation markers are more likel y consequences of but not inducers of HIV-1 replication. (C) 2001 Lippincot t Williams & Wilkins.