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The Washington Blade
Liver dysfunction monitoring urged with d4T
Lisa Keen
August 11, 2000
The Washington Blade - August 11, 2000

One of the most commonly prescribed nucleoside analogs -- d4t or stavudine -- may be capable of causing a life-threatening liver dysfunction in a small percentage of patients, notes an article from a National Institutes of Health team. The syndrome -- known as hepatic steatosis and lactic acidosis -- had been associated with use of two other nucleosides, AZT and ddI, since the early 1990s. It causes fat degeneration in the liver, accumulation of lactic acid, and disease of the muscles.

The NIH team, reporting in the Aug. 1 issue of the Annals of Internal Medicine, said it found four patients, diagnosed in 1997, who also appeared to have the symptoms as a result of taking d4t.

d4t is the second most widely used nucleoside, noted the report. It is produced by Bristol Myers Squibb and marketed under the name Zerit.

"Initial symptoms may be mild and nonspecific, such as nausea and abdominal discomfort," noted the authors, "this may lead to a delay in diagnosis until patients are severely ill." The team recommended doctors monitor patients on d4T every three to four months to watch for symptoms and to consider nutritional supplements for possible deficiencies in riboflavin and thiamine.

Warning on abacavir: Avoid interruptions And with all the recent focus on "strategic treatment interruption," the Glaxo Wellcome pharmaceutical company decided it was a good idea July 27 to send out a reminder notice to doctors that stopping and starting its nucleoside analog abacavir could have potentially life-threatening consequences.

The Food and Drug Administration approved the nucleoside analog (sold under the trade name Ziagen) in December 1998 and noted, at that time, that about five percent of patients who take the medication had a "potentially fatal" allergic reaction to it. The letter July 27 notes, however, that "severe or fatal" reactions can occur in people who have not previously shown any allergy to the medication. It urges doctors to be sure that patients who stop taking abacavir are not allergic to the drug before starting the medication again and that restarting the drug should take place "only if medical care can be readily accessed by the patient and others." One of the less publicized but more interesting reports at the International Conference on AIDS last month -- a report from Spain -- was a psychological study of the appeal of being able to stop taking the burdensome pill regimens required by most triple drug therapies. The researchers found that the appeal is so great that "patients are more interested in stopping their therapy than in controlling the virus." In brief ...

ABT-378: Abbott Laboratories� new once-a-day protease inhibitor, ABT-378, is now more widely available. The drug is intended for use with Abbott�s other protease inhibitor, ritonavir. According to a press release from the company Aug. 4, the antiviral, also known as lopinavir, has been available to only certain patients with HIV and specific criteria, due to the company�s limited supply. People with HIV interested in obtaining ABT-378 should call Abbott at (888) 711-7193.

CHECKING FOR TB: The U.S. Centers for Disease Control and Prevention reiterated a warning this month that all people with HIV who have any close contact with tuberculosis should be evaluated for TB infection and, even if they test negative for TB, should be given preventive treatment. In the Aug. 4 Morbidity and Mortality Weekly Report, the agency noted that people who are in close contact with people who have active tuberculosis -- either prolonged periods of time, frequently, or physically close -- are at significant risk of contracting TB. The agency studied more than 8,000 people in "close contact" with tuberculosis in 11 cities and identified 109 who also had HIV infection.

Nineteen percent of those with HIV infection also had active tuberculosis, compared to only 2 percent of the people who did not report having HIV.

SALVAGE POSSIBILITIES: A study in London, reported at an HIV treatment conference in Spain in June, indicated that a salvage therapy of five drugs -- efavirenz, hydroxyurea, ddI, ritonavir, indinavir -- appeared to successfully suppress HIV in two-thirds of 92 patients who had failed on a protease inhibitor combination. At this same conference, a separate report found that about 41 percent of 52 patients who had failed two previous combination regimens experienced success on a four-drug salvage regimen of efavirenz, hydroxyurea, ddI, and nelfinavir.

NON-NUKE VULNERABILITY: A study from three countries, including the U.S., and presented at the HIV treatment conference in Spain found that "The prevalence of resistance to [non-nucleoside analogs] is approaching 50 percent and has implications" for the successful use of these drugs in treating HIV. Non-nucleosides include efavirenz, nevirapine, and delavirdine. Overall, noted the report, only 21.8 percent of 11,990 blood samples tested were still sensitive to all types of anti-HIV medications.