ABSTRACT
This study compared the efficacies of clarithromycin-ethambutol and clarithromycin-ethambutol-clofazimine for the treatment of Mycobacterium avium complex (MAC) in AIDS patients. Thirty-four patients were randomized into two groups to receive clarithromycin 2 g/day and ethambutol 20 mg/kg/day, with or without clofazimine 200 mg/day. The evaluation was based primarily on blood cultures becoming negative after 2 months of therapy, but survival at 12 months and clinical evolution were also assessed. Inclusions were prematurely stopped because of a communication reporting increased mortality associated with clofazimine. At 2 months, the blood cultures of 55% of the clarithromycin-ethambutol group patients versus 81% of the clarithromycin-ethambutol-clofazimine group were negative; this difference is not significant (P=0.42). Only one relapse was observed during the study. No clarithromycin-resistant strain was isolated. No apparent difference in either survival or clinical evolution was observed in this small number of patients (median survival, 144 days in the clarithromycin-ethambutol group and 236 days in the clarithromycin-ethambutol-clofazimine group, P=0.44). The clarithromycin-ethambutol combination appears to be an effective and well-tolerated first-line therapy against MAC infections in AIDS patients.
Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Bacteremia/drug therapy , Clarithromycin/therapeutic use , Clofazimine/therapeutic use , Ethambutol/therapeutic use , Mycobacterium avium-intracellulare Infection/drug therapy , Aged , Drug Therapy, Combination/therapeutic use , Female , Humans , Male , Middle Aged , Mycobacterium avium Complex , Survival AnalysisSubject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/immunology , Immunoglobulin Heavy Chains/physiology , Immunoglobulin Variable Region/physiology , Adult , Aged , Child , Child, Preschool , Down-Regulation , Drug Therapy, Combination , Female , HIV Protease Inhibitors/therapeutic use , Humans , Immunoglobulin Fragments , Immunoglobulin G/blood , Immunoglobulin G/metabolism , Immunoglobulin Heavy Chains/blood , Immunoglobulin Variable Region/blood , Lymphokines/metabolism , Male , Middle Aged , Reverse Transcriptase Inhibitors/therapeutic use , Sialoglycoproteins/metabolism , Superantigens/immunologyABSTRACT
The interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system is the main regulatory determinant of T cell reactivity. Although it is well known that IL-2 secretion is impaired during HIV infection, up to now IL-2R expression has not been extensively studied in HIV-infected patients despite the use of IL-2 in clinical therapy trials. We show here that IL-2R expression in HIV patients with high viral load (group 1 in the study) is greatly enhanced on B lymphocytes, CD8 T lymphocytes, and monocytes, but not on CD4 T lymphocytes, compared with noninfected individuals. Paradoxically, this modified IL-2R expression does not lead to increased IL-2 responsiveness, except for B lymphocytes. In patients receiving triple combination therapy (TCT, two reverse transcriptase inhibitors and one protease inhibitor) that has triggered a drastic reduction in plasma viral load and an increase in CD4 counts (group 2 patients), IL-2R expression is significantly lower than in group 1 patients. Moreover, cells involved in cellular immunity and CD4 T lymphocytes have the capacity to respond to IL-2 after TCT. These results allow us to anticipate a beneficial role of IL-2 immunotherapy in combination with TCT.
