Trial Information

A Phase I Trial to Evaluate Azidothymidine (AZT) in the Treatment of HIV Infections in Patients With Hemophilia

There is a clear risk for development of AIDS in hemophilic patients. AZT administration has
been shown to inhibit HIV replication in vitro. Patients taking AZT have experienced fewer
opportunistic infections and improvements in measures of immunity. The most common
laboratory abnormalities observed with AZT are hematologic. However, the clinical and
laboratory toxicity of AZT remains poorly understood in hemophiliacs. Hepatitis and liver
dysfunction are more common in this population compared to other groups at risk for HIV
infection. Because AZT is largely metabolized in the liver, drug pharmacokinetics needs to
be evaluated in this patient population.

Both hemophiliacs and non-hemophiliacs take AZT for a period of 12 weeks. The first dose is
administered intravenously. AZT is then given orally every 4 hours while awake (5 doses per
day). Patients are evaluated by physical examinations and laboratory assessments. These
include HIV culture of blood and leukocyte counts, lymphocyte counts, and lymphocyte subsets
measured at study entry and every 4 weeks thereafter. Patients are hospitalized for
pharmacokinetic studies at study entry and at Weeks 6 and 12. Each of these studies involves
both intravenous and oral administration within 48 hours of one another. Blood is sampled at
0, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after each administration and urine is collected
every 2 hours for 12 hours.