GMHC Treatment Issues, No. 43; Volume 4 Number 3 -- May 22, 1990
Gabriel Torres, M. D.

Absorption

A group from the University of Washington studied absorption of AZT taken with or without a high-fat meal. They found that AZT taken on an empty stomach is rapidly absorbed, with the highest blood level achieved 40 minutes after taking the drug. If AZT is taken with a high-fat meal, the blood level is reduced by almost 50% and the time necessary to achieve that level is prolonged. A low blood level of the drug may not achieve adequate inhibition of the virus. The investigators recommend that patients refrain from taking AZT with or immediately after a meal.

Esophageal Ulcers

In another report from Australia, three patients who took AZT capsules on a 24-hour schedule developed ulcers in the esophagus (the conduit connecting the mouth to the stomach). The patients took the capsules without any fluid while lying in bed in the early morning hours. They developed difficulty and pain on swallowing due to multiple ulcers on the esophagus at the level of the aortic arch. The authors of the report recommend that AZT capsules be taken in an upright position with at least 120 milliliters of water.

Nail Discoloration

Skin side effects related to AZT have ranged from allergic reactions such as itchy red rashes over the entire body to changes in the color of fingernails and toenails. One recent paper reported on sixteen patients with AIDS or ARC who developed nail discoloration (dyschromia) within four to eight weeks of starting AZT therapy. Most had long dark streaks in their nails; a few had transverse bands. Sixty-seven percent of the patients with this nail discoloration were black, and 31% were white or Hispanic. The authors of the report recommend that physicians inform patients of the possibility of developing nail discoloration due to AZT, since often this disorder may be confused with melanoma, a skin cancer related to sun exposure. How this occurs in unknown, but it may be due to a direct effect of AZT on the cells that produce skin pigment which are numerous in persons with dark skin.

Muscle Wasting

Several reports have described an association between chronic AZT usage and the development of myopathy (muscle inflammation). HIV itself can also cause a myopathy with severe muscle weakness due to inflammation of the muscle fibers. This inflammation usually responds to steroid therapy such as prednisone. A recent article in the New England Journal of Medicine identified criteria for distinguishing HIV-related myopathy from AZT-related myopathy. Twenty HIV-positive patients with myopathy underwent muscle biopsy. Fifteen who had received AZT had numerous "ragged red" fibers indicative of abnormal mitochondria, a finding which was not present in the five patients with HIV-related myopathy who had never received AZT. Mitochondria are organelles inside cells which produce energy for metabolism and other cellular functions. In four patients, the myopathy improved with prednisone therapy and discontinuation of AZT. In seven patients, muscle strength improved and returned to normal from seven to ten days after AZT was discontinued. In two patients, AZT was restarted at lower doses six months later, but the muscle weakness recurred and the drug had to be discontinued permanently. Of the five patients with HIV-related myopathy, two responded to prednisone, one died, one improved with AZT, and one improved with ibuprofen (Motrin or Advil). The muscle biopsies in these patients showed inflammatory T cells and macrophages surrounding the dead muscle fibers. The mean time on AZT before development of the mitochondrial myopathy was 12.8 months.

Another potential cause of myopathy is suggested by the finding of T8 cells in the dead muscle tissue, since T8 cells can release substances which are toxic and can damage cells. The authors of the report recommend nonsteroidal, anti-inflammatory agents for patients who develop symptoms of myopathy before discontinuation of AZT. If this is not effective, AZT should be discontinued for 3-4 weeks, and the patients' level of strength and muscle enzymes (CPK level) should be monitored. If the strength does not return, prednisone should be started at a dose of 40-60 mg/day. Muscle biopsies should be done in patients where the diagnosis is unclear.

AZT for Children

In May, the FDA approved AZT for children. This decision was based on results from two small studies which followed 124 children for about one year. Improvements were seen in immune system function, incidence of opportunistic infections, neurological symptoms and other clinical parameters. As in adults, the major toxicities were anemia and low white cell counts. The recommended dose, to be given as a strawberry- flavored syrup is 180 mg/square meter of body surface every six hours, not to exceed 200 mg every six hours.

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