Use of Zidovudine

Abstract

Zidovudine (Retrovir, AZT) was first used in clinical trials in 1986. The article from St Stephen's Hospital which appears in this issue summarizes the experience of routine use of the drug by a single centre. It seems a good time to take stock of the present state of knowledge of the drug and to summarize what has been learnt over the last two years. Experience gained from developing zidovudine will help us to predict the difficulties of future assessment of any new anti-HIV drugs. In the original trial [1,2] (of 282 patients) zidovudine showed great efficacy when it was given for 16 weeks to HIV-positive patients. Entry criteria included patients who either had a single episode of proved Pneumocystis carinii pneumonia or who had symptoms of classical ARC (weight loss or oral candidiasis and either fever, night sweats, herpes zoster, oral hairy leukoplakia or unexplained diarrhoea). That original trial was stopped prematurely because of the great reduction in mortality of the treated group (19 vs. 1 death). Follow up data on that trial, however, show that patients on long-term treatment do still die from the results of opportunistic infections [1]. It is therefore a great pity that no placebo-controlled trial on other patient groups has yet been published which would help to define, more precisely, the efficacy and toxicity of this expensive drug. The International Conference on AIDS in June 1988 provided more data on the open use of zidovudine. About a dozen different groups reported their experiences and all agreed that the drug was 'well tolerated' and showed short term improvement in 'well being'. Unfortunately, all centres agreed that patients with AIDS still die of opportunistic infection in spite of treatment with zidovudine. None of these studies tested or enlarged on the conclusions of the original 1986 trial. In view of the lack of useful trials on zidovudine, it is to be regretted that medical ethics have inhibited the implementation of trials even in countries where the drug is too expensive for general use. In spite of the lack of trials the increase in the use of zidovudine over the last two years is now a matter of history. The drug is widely prescribed to all patients with true AIDS (as defined by the Communicable Diseases Centre, United Kingdom), and many symptomatic patients with ARC or neurological disease, even though no placebo-controlled trials have demonstrated efficacy in these groups. Some clinicians have been tempted to treat asymptomatic patients who have laboratory signs of progression (e.g. falling T4 cells, development of p24 antigenaemia or rising /?2-microglobulinaemia) in the hope of preventing disease progression. In the absence of any other treatment, health care workers who have had a major parenteral exposure to HIV-infected blood have been offered conventional doses of zidovudine for an arbitrary six weeks. In the absence of long-term controlled trials, the group in St Stephen's Hospital has