FDA is receiving inquiries about results of a European study of the clinical benefits of zidovudine (AZT) in people infected with the human immunodeficiency virus (HIV) who have not yet developed symptoms of AIDS. The partial results of the study, known as the Concorde trial, have been reported in a letter published in the journal Lancet.
The following may be used to respond to questions.
The partial results reported in Lancet show no difference in clinical outcomes between people with asymptomatic HIV who received AZT early in the course of the disease, and those treated initially with a placebo followed by AZT treatment when AIDS symptoms appeared. The authors of the study also claim to have found no connection between the increases in CD4 cell counts and the patients' condition after a period of three years.
It is important to note that studies have shown AZT provides clinical benefits to patients for 12 to 18 months. For patients treated with AZT for longer periods, the drug's benefits appear to decrease substantially.
The study reported in Lancet does not call into question the clinical importance of AZT in treating symptomatic HIV disease or the relevance of early CD4 cell count changes in predicting the short term benefits of drugs like AZT.
FDA believes this report clearly shows the need for continued studies of AZT and other AIDS products to ensure that the usefulness of the drugs is fully understood. It will be important to explore what factors, such as viral resistance, may be responsible for decreases in benefits of the drugs over time.
The Concorde study documents the need for trials that include clinical outcome data -- the effect of the drug on the course of the disease -- and the need for postmarketing surveillance for drugs approved on the basis of surrogate markers such as CD4 cell counts.
FDA is looking forward to reviewing the data referred to in the Lancet letter, particularly those pertaining to use of surrogate markers to predict clinical outcomes. Careful review and discussion with expert consultants will allow the agency to place the study in perspective and will indicate whether any changes in labeling for AZT are warranted.
2 Kaplan-Meier estimate of the time at which 50% of the group would have experienced their first interruption of ZDV treatment.