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STEP
Opportunistic Infections & Other Complications: Mycobacterium Avium Complex (MAC)
Laury McKean, RN
March 10, 1993
Seattle Treatment Education Project (STEP) Perspective, Vol. 5, No. 2 -

MAC (also called MAI) infection frequently occurs in HIV positive individuals. It typically occurs with lower CD4 counts, the majority of cases seen in individuals with CD4 counts less than 100 combined with CD8 counts less than 500. A Swiss study presented at last year's conference concluded MAC has become twice as prevelant as pcp and that individuals with CD4 counts less than 50 are at higher risk for developing MAC than individuals with CD4 counts less than 200 are for getting pcp who are not receiving prophylaxis. With more and more individuals living for long periods of time with low CD4 counts, the issue of MAC prophylaxis is becoming crucial.

Two randomized, double-blind clinical trials (023 and 027) compared rifabutin 300 mg/day to placebo in individuals with AIDS and CD4 counts equal to or less than 200. These studies, which enrolled a total of 1146 people, showed that individuals who received rifabutin were significantly less likely to develop MAC than were the individuals who received placebo. As a result of these studies, rifabutin was approved for MAC prophylaxis in December 1992.

Despite the drug's approval, many physicians have been reluctant to initiate rifabutin prophylaxis in individuals at risk. Some felt that prophylaxis might result in increased drug resistance to treatment if the individuals developed MAC infection despite prophylaxis. A poster presented at the conference examined this issue. Individuals who developed MAC bacteremia in the 023 and 027 MAC prophylactic studies were allowed to receive rifabutin for treatment. Both rifabutin (600 mg a day) and simultaneous antimycobacterial drugs were recommended. Of 13 individuals who had previously received rifabutin prophylaxis, MAC was eradicated from the blood in 62%. Similarly, MAC was eradicated from the blood in 69% of 42 individuals who had previously received placebo in the prophylaxis studies. The investigators concluded that prior rifabutin prophylaxis therapy does not impact the therapeutic response when rifabutin is administered for the treatment of MAC infection (po-b07-1237).

Three posters were presented at the conference examining the use of clarithromycin for prophylaxis of mac. All three showed encouraging results. In one small study, 19 individuals with a mean CD4 count of 43 (range 10-100) received 500 mg of clarithromycin a day for a mean follow up period of six months. None of the individuals developed symptomatic mac, although one individual did have MAC cultured from serial sputum samples after 33 weeks of prophylaxis. None of the individuals discontinued therapy due to adverse effects (po-b07-1185). Another poster presented a retrospective study of 43 individuals with CD4 counts less than 100 (average 36.6). These individuals took low dose clarithromycin ranging from 250 to 1000 mg a day for primary prevention of mac. The average time on clarithromycin was 11.7 months. None of the 43 individuals developed MAC disease (po-b07-1237). The third poster, also a retrospective study, showed clarithromycin (as well as rifabutin) to be an effective prophylaxis. This study compared individuals receiving clarithromycin and rifabutin with individuals receiving no prophylaxis. Fifty individuals with CD4 count under 200 (41 were under 50) received 500 mg of clarithromycin a day for an average of 5.3 months and none of the individuals developed MAC bacteremia. Eighteen individuals, all with CD4 counts less than 50, received 300 mg of rifabutin a day for an average of 6.7 months and one individual developed MAC bacteremia. This was compared to 58 individuals who received no MAC prophylaxis, 14 of whom developed MAC bacteremia during a comparable observation period (po-b07-1184).

Previously, many physicians chose not to treat MAC disease because often the side effects of the old four or five drug regimens outweighed the benefits of treatment. However, with the recent advances in research, treatment is now clearly associated with a reduction in mycobacterial load and an improvement in symptoms. In a presentation by Dr. Tim Church, treatment was associated with improved survival, especially with the use of clarithromycin, azithromycin, or ethambutol (WS-B10-6). The risk may be further reduced by using combinations of these and other agents.

In an evening symposium, Dr. Constance Benson discussed the treatment for MAC disease. Clarithromycin (500 mg to one gram twice a day) appears to be the most active agent. However, resistance emerges within a few months when administered as a monotherapy, so it should always be combined with at least one other drug. Ethambutol (15 mg/kg a day) appears to be the drug of choice for a second agent. The decision to use more than two drugs should be individualized. If a third drug is added, clofazimine (100 to 200 mg a day) appears to be a favorable choice, however rifabutin (600 mg a day) may prove to be superior as it may actually enhance the efficacy of ethambutol (Management of MAC in Patients with HIV Infection, 6-8-93, Berlin).

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