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).
Benson
C A
CA
Rush Medical College/Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA. constance.benson@uchsc.edu
Williams
P L
PL
Cohn
D L
DL
Becker
S
S
Hojczyk
P
P
Nevin
T
T
Korvick
J A
JA
Heifets
L
L
Child
C C
CC
Lederman
M M
MM
Reichman
R C
RC
Powderly
W G
WG
Notario
G F
GF
Wynne
B A
BA
Hafner
R
R
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use*; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D017828:Rifabutin / Q000008:administration & dosage / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D017828:Rifabutin; D017291:Clarithromycin