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

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 Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related.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.