Use of Clarithromycin Prophylaxis Reduces MAC Infection, Mortality in Advanced AIDS Patients

SAN FRANCISCO-Clarithromy-cin (Biaxin), a newer generation macro-lide,has been shown to have a definite favorable effect on survivalwhen given prophylactically to patients with advanced AIDS, MarkPierce, MD, reported at the 35th Interscience Conference on AntimicrobialAgents and Chemotherapy.

The positive survival benefit is due primarily to clarithromy-cin'sability to prevent Mycobacterium avium complex (MAC) infection,which predicts mortality in patients with advanced HIV infection,said Dr. Pierce, associate professor of medicine and infectiousdiseases, Vanderbilt University School of Medicine.

Dr. Pierce presented the data for the Clarithromycin MAC ProphylaxisTreatment Group: France, Germany, United Kingdom, and the UnitedStates, sponsored by Abbott Laboratories.

The prospective, randomized, double-blind, multicenter trial,conducted in the United States and Europe, enrolled 682 HIV-positivepatients with CD4 cell counts less than 100/mm³, negativeMAC blood cultures, and a life expectancy of at least 6 months.These individuals were split into two groups of 341 persons each,and randomly assigned to receive clarith-romycin, 500 mg twicedaily, or placebo indefinitely.

During the study and follow-up, Dr. Pierce pointed out, 19 personsin the clarithromycin group (5.7%) developed MAC infection, comparedwith 53 individuals on placebo (15.9%), a 69% reduction in riskin favor of clarithromycin. (Mean time on treatment was 9.1 monthsfor placebo patients and 10.1 months for the clarithromycin group.)

The most recent analysis shows median survival of more than 700days in those patients who received clarithromy-cin vs 573 daysin the placebo group, again a significant difference in favorof clarithromycin.

Death has occurred in 106 persons receiving clarithromycin (31%)and in 136 individuals receiving placebo (39%), for a reductionin all-cause mortality of 28% when patients were treated withclarithromycin.

The data in this study demonstrated definitively that disseminatedMAC infection is a predictor of mortality in patients with advancedAIDS, Dr. Pierce said. After controlling for baseline and currentCD4 counts, placebo recipients who became MAC positive duringthe study had a relative risk of death of 2.6, compared with thosepatients who were MAC negative.

An evaluation of the MAC isolates in the patients who developedMAC infection while on clarithromycin showed that 11 (58%) ofthe 19 breakthrough isolates were resistant to clarithromycin.