Literature DB >> 1346505

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 Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related.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

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Year:  1992        PMID: 1346505      PMCID: PMC1880952          DOI: 10.1136/bmj.304.6818.13

Source DB:  PubMed          Journal:  BMJ        ISSN: 0959-8138


  13 in total

1.  A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

Authors:  M A Fischl; C B Parker; C Pettinelli; M Wulfsohn; M S Hirsch; A C Collier; D Antoniskis; M Ho; D D Richman; E Fuchs
Journal:  N Engl J Med       Date:  1990-10-11       Impact factor: 91.245

2.  Effects of zidovudine in 365 consecutive patients with AIDS or AIDS-related complex.

Authors:  E Dournon; S Matheron; W Rozenbaum; S Gharakhanian; C Michon; P M Girard; C Perronne; D Salmon; P De Truchis; C Leport
Journal:  Lancet       Date:  1988-12-03       Impact factor: 79.321

3.  HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy.

Authors:  B A Larder; G Darby; D D Richman
Journal:  Science       Date:  1989-03-31       Impact factor: 47.728

Review 4.  Rational choice of dose: insufficient background knowledge?

Authors:  P C Gøtzsche; E F Hvidberg; P Juul
Journal:  Ration Drug Ther       Date:  1986-07

5.  Serial CD4 lymphocyte counts and development of AIDS.

Authors:  A N Phillips; C A Lee; J Elford; G Janossy; A Timms; M Bofill; P B Kernoff
Journal:  Lancet       Date:  1991-02-16       Impact factor: 79.321

6.  Declining incidence of AIDS dementia complex after introduction of zidovudine treatment.

Authors:  P Portegies; J de Gans; J M Lange; M M Derix; H Speelman; M Bakker; S A Danner; J Goudsmit
Journal:  BMJ       Date:  1989-09-30

7.  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.

Authors:  H Mitsuya; K J Weinhold; P A Furman; M H St Clair; S N Lehrman; R C Gallo; D Bolognesi; D W Barry; S Broder
Journal:  Proc Natl Acad Sci U S A       Date:  1985-10       Impact factor: 11.205

8.  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

Authors:  D D Richman; M A Fischl; M H Grieco; M S Gottlieb; P A Volberding; O L Laskin; J M Leedom; J E Groopman; D Mildvan; M S Hirsch
Journal:  N Engl J Med       Date:  1987-07-23       Impact factor: 91.245

9.  Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy.

Authors:  C A Boucher; M Tersmette; J M Lange; P Kellam; R E de Goede; J W Mulder; G Darby; J Goudsmit; B A Larder
Journal:  Lancet       Date:  1990-09-08       Impact factor: 79.321

10.  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.

Authors:  P A Volberding; S W Lagakos; M A Koch; C Pettinelli; M W Myers; D K Booth; H H Balfour; R C Reichman; J A Bartlett; M S Hirsch
Journal:  N Engl J Med       Date:  1990-04-05       Impact factor: 91.245

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  15 in total

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Authors:  H D Langtry; K J Palmer; P Benfield
Journal:  Pharmacoeconomics       Date:  1993-04       Impact factor: 4.981

Review 2.  Treatment of HIV infection. Tolerability of commonly used antiretroviral agents.

Authors:  D W Notermans; R van Leeuwen; J M Lange
Journal:  Drug Saf       Date:  1996-09       Impact factor: 5.606

Review 3.  Zidovudine therapy in HIV infection: which patients should be treated and when.

Authors:  M G Barry; D J Back; A M Breckenridge
Journal:  Br J Clin Pharmacol       Date:  1995-08       Impact factor: 4.335

Review 4.  Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A Review.

Authors:  Pablo S Rivadeneira; Claude H Moog; Guy-Bart Stan; Cecile Brunet; François Raffi; Virginie Ferré; Vicente Costanza; Marie J Mhawej; Federico Biafore; Djomangan A Ouattara; Damien Ernst; Raphael Fonteneau; Xiaohua Xia
Journal:  Biores Open Access       Date:  2014-10-01

Review 5.  Pharmacokinetic individualisation of zidovudine therapy. Current state of pharmacokinetic-pharmacodynamic relationships.

Authors:  R M Hoetelmans; D M Burger; P L Meenhorst; J H Beijnen
Journal:  Clin Pharmacokinet       Date:  1996-04       Impact factor: 6.447

Review 6.  Antiviral therapy in human immunodeficiency virus infections. Current status (Part II).

Authors:  E Sandström; B Oberg
Journal:  Drugs       Date:  1993-05       Impact factor: 9.546

Review 7.  The effects of long term zidovudine therapy and Pneumocystis carinii prophylaxis on HIV disease. A review of the literature.

Authors:  D R Hoover
Journal:  Drugs       Date:  1995-01       Impact factor: 9.546

Review 8.  Review of antiretroviral therapy in the prevention of HIV-related AIDS dementia complex (ADC).

Authors:  P Portegies
Journal:  Drugs       Date:  1995       Impact factor: 9.546

Review 9.  Zidovudine. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Authors:  Michelle I Wilde; Heather D Langtry
Journal:  Drugs       Date:  1993-09       Impact factor: 9.546

10.  Development of an optimized dose for coformulation of zidovudine with drugs that select for the K65R mutation using a population pharmacokinetic and enzyme kinetic simulation model.

Authors:  Selwyn J Hurwitz; Ghazia Asif; Nancy M Kivel; Raymond F Schinazi
Journal:  Antimicrob Agents Chemother       Date:  2008-10-06       Impact factor: 5.191

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