Double blind dose-response study of zidovudine in AIDS and advanced HIV infection. Nordic Medical Research Councils' HIV Therapy Group.

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Abstract
OBJECTIVE--To compare the efficacy and side effects of 400 mg, 800 mg, and 1200 mg zidovudine daily in patients with AIDS or advanced HIV infection. DESIGN--Randomised, double blind, parallel group multicentre study. SETTING--Hospital departments of infectious diseases and dermatology in Denmark, Sweden, Norway, Finland, and Iceland. SUBJECTS--474 patients: 126 (27%) with AIDS; 248 (52%) with HIV related symptoms; 100 (21%) with low CD4+ cell counts. INTERVENTIONS--Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All patients received one capsule from each of three bottles four times daily. MAIN OUTCOME MEASURES--Survival; incidence of new HIV related events; CD4+ cell count; quality of life; incidence of haematological side effects. RESULTS--460 (97%) of the 474 patients had not received zidovudine previously. The median follow up period was 19 months, during which the death rates in the three treatment groups were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p = 0.49; log rank test). One year after the trial was terminated the death rates were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There was no significant difference between the groups in time to a new AIDS defining event or death, average number of events per patient, decline in CD4+ cell counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related. CONCLUSION--Zidovudine should be limited to 400-600 mg daily in patients with AIDS or advanced HIV infection.