Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team.

The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had < or =100 CD4 T cells/microL in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4. 7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P=.005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P=. 0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P=.36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P<.001).

A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team.

OBJECTIVE: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. DESIGN: A randomized, open-labeled, comparative trial. SETTING: Outpatient clinics. PATIENTS: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. INTERVENTIONS: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. MAIN OUTCOME MEASURE: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. RESULTS: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. CONCLUSIONS: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.

Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group.

OBJECTIVE: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. DESIGN: A randomized, double-blind study. SETTING: 24 U.S. academic medical centers. PATIENTS: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. INTERVENTION: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. MEASUREMENTS: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. RESULTS: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01). CONCLUSIONS: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.