Skip to main content
PMC home page
The BMJ logoLink to The BMJ
. 1992 Jan 4;304(6818):13–17. doi: 10.1136/bmj.304.6818.13

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

PMCID: PMC1880952  PMID: 1346505

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 Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related.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

Full text

PDF
15

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boucher C. A., Tersmette M., Lange J. M., Kellam P., de Goede R. E., Mulder J. W., Darby G., Goudsmit J., Larder B. A. Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy. Lancet. 1990 Sep 8;336(8715):585–590. doi: 10.1016/0140-6736(90)93391-2. [DOI] [PubMed] [Google Scholar]
  2. Dournon E., Matheron S., Rozenbaum W., Gharakhanian S., Michon C., Girard P. M., Perronne C., Salmon D., De Truchis P., Leport C. Effects of zidovudine in 365 consecutive patients with AIDS or AIDS-related complex. Lancet. 1988 Dec 3;2(8623):1297–1302. doi: 10.1016/s0140-6736(88)92903-0. [DOI] [PubMed] [Google Scholar]
  3. Fischl M. A., Parker C. B., Pettinelli C., Wulfsohn M., Hirsch M. S., Collier A. C., Antoniskis D., Ho M., Richman D. D., Fuchs E. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. N Engl J Med. 1990 Oct 11;323(15):1009–1014. doi: 10.1056/NEJM199010113231501. [DOI] [PubMed] [Google Scholar]
  4. Fischl M. A., Richman D. D., Causey D. M., Grieco M. H., Bryson Y., Mildvan D., Laskin O. L., Groopman J. E., Volberding P. A., Schooley R. T. Prolonged zidovudine therapy in patients with AIDS and advanced AIDS-related complex. AZT Collaborative Working Group. JAMA. 1989 Nov 3;262(17):2405–2410. [PubMed] [Google Scholar]
  5. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  6. Gøtzsche P. C., Hvidberg E. F., Juul P. Rational choice of dose: insufficient background knowledge? Ration Drug Ther. 1986 Jul;20(7):1–7. [PubMed] [Google Scholar]
  7. Larder B. A., Darby G., Richman D. D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989 Mar 31;243(4899):1731–1734. doi: 10.1126/science.2467383. [DOI] [PubMed] [Google Scholar]
  8. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. N., Gallo R. C., Bolognesi D., Barry D. W., Broder S. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096–7100. doi: 10.1073/pnas.82.20.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Phillips A. N., Lee C. A., Elford J., Janossy G., Timms A., Bofill M., Kernoff P. B. Serial CD4 lymphocyte counts and development of AIDS. Lancet. 1991 Feb 16;337(8738):389–392. doi: 10.1016/0140-6736(91)91166-r. [DOI] [PubMed] [Google Scholar]
  10. Portegies P., de Gans J., Lange J. M., Derix M. M., Speelman H., Bakker M., Danner S. A., Goudsmit J. Declining incidence of AIDS dementia complex after introduction of zidovudine treatment. BMJ. 1989 Sep 30;299(6703):819–821. doi: 10.1136/bmj.299.6703.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  12. Volberding P. A., Lagakos S. W., Koch M. A., Pettinelli C., Myers M. W., Booth D. K., Balfour H. H., Jr, Reichman R. C., Bartlett J. A., Hirsch M. S. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941–949. doi: 10.1056/NEJM199004053221401. [DOI] [PubMed] [Google Scholar]
  13. Yarchoan R., Klecker R. W., Weinhold K. J., Markham P. D., Lyerly H. K., Durack D. T., Gelmann E., Lehrman S. N., Blum R. M., Barry D. W. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986 Mar 15;1(8481):575–580. doi: 10.1016/s0140-6736(86)92808-4. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES