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Zidovudine in Patients with HIV Infection
- Heiner C. Bucher, MD, MPH; and
- Lauren Griffith, MS
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TO THE EDITOR:
We question the validity of the subgroup analysis in the recent report by Ioannidis and colleagues [1] and disagree with the authors' assertion that there is a trend toward delayed progression of human immunodeficiency virus (HIV) disease in long-term trials of early compared with delayed zidovudine treatment. The inclusion of the Azidothymidine Collaborative Working Group (AZTCG) follow-up study [2] in the subgroup analysis contradicts the eligibility criteria initially established by the authors. A valid comparison of the long-term effectiveness of zidovudine from this trial is impossible because both the former placebo group and the treatment group received zidovudine.
We have done a subgroup analysis according to CD4 cell count at study entry in nine randomized trials of early compared with delayed zidovudine therapy. We excluded the AZTCG follow-up study and integrated additional information as collected from the authors of the original trials.
The risk ratio for progression to the acquired immunodeficiency syndrome or death in long-term trials (> 21 months' duration), regardless of the patients' initial CD4 status, was 0.96 (95% CI, 0.81 to 1.13). For short-term trials (< 14 months' duration), risk for progression was 0.43 (CI, 0.32 to 0.59) (Table 1). The risk ratio for progression to AIDS or death in short-term trials for patients with CD4 counts of 200 to 499 cells/mm3 was 0.42 (CI, 0.29 to 0.60). For patients with CD4 counts less than 200 cells/mm3, the risk ratio was 0.57 (CI, 0.34 to 0.95). In long-term trials, however, the corresponding risk ratio was 0.91 (CI, 0.61 to 1.36) for patients with more than 500 CD4 cells/mm3, 0.94 (CI, 0.78 to 1.13) for patients with 200 to 499 CD4 cells/mm3, and 1.27 (CI, 0.96 to 1.66) for patients with fewer than 200 CD4 cells/mm3.
Ioannidis and colleagues' meta-analysis more adequately shows the transient effectiveness of zidovudine in various stages of HIV infection but shows no beneficial effect in long-term trials. In addition, we are concerned that long-term treatment with zidovudine in patients with advanced HIV infection (< 200 CD4 cells/mm sup 3) may even be harmful.
Heiner C. Bucher, MD, MPH
Lauren Griffith, MS
McMaster University Medical Centre
Hamilton, Ontario L8N 3Z5, Canada
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
