Correspondence

Zidovudine and the Quality of Life

N Engl J Med 1994; 331:332-333August 4, 1994

Article

To the Editor:

We disagree with the conclusion of Lenderking et al. (March 17 issue)1 that the side effects of zidovudine make its use questionable in patients who have asymptomatic human immunodeficiency virus (HIV) infection. The most striking finding of the study was that there was no difference in symptomatic adverse events between the placebo group and the group treated with the recommended daily dose of 500 mg of zidovudine. The only difference was in “metabolic abnormalities” observed on laboratory analysis. It is difficult to understand how patients could regard a laboratory abnormality as affecting the quality of life as much as an opportunistic infection or progressive dementia. If indeed patients' perceptions are such, then perhaps they should receive more explanation to help them understand the relative importance of events.

The premise that there is no survival advantage among zidovudine-treated patients is also questionable. As reported in the study by Lenderking et al., there were no AIDS-related deaths in the group treated with the usual dose of zidovudine and four such deaths in the placebo group. With larger groups a survival advantage might be found, particularly if combination regimens were used.

The reaction of the public and many patients with HIV infection to this study as presented by the media is, “You see, we knew AZT [zidovudine] was no good.” Such a message is not in the interest of HIV-infected patients. We believe that zidovudine alone or combined with other therapy, with proper monitoring and dosages, has an important role in the treatment of HIV disease.

Daniel S. Berman, M.D.
Barry D. Wenglin, M.D.
56 Doyer Ave., White Plains, NY 10605

1 References

1. 1

   Lenderking WR, Gelber RD, Cotton DJ, et al. Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. N Engl J Med 1994;330:738-743
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree with Drs. Berman and Wenglin that zidovudine has an important role in the management of HIV disease. The results of our Q-TWiST (quality-adjusted time without symptoms and toxicity) analyses of AIDS Clinical Trials Group Protocol 019 (as described in our article) and Protocol 016 (as described elsewhere1) support either early initiation of zidovudine treatment or delayed administration of the drug. The preference of Berman and Wenglin for early initiation of treatment is based on their conviction that the side effects of a daily dose of 500 mg of zidovudine are trivial as compared with progression of HIV disease. Indeed, if a patient assigns full value to the time after an adverse event and no value to the time after disease progression, then our analysis demonstrates that zidovudine therapy provides significantly more Q-TWiST than placebo (Figure 3 of our article). A different set of patients' preferences was implied by reports in the media suggesting that the duration of side effects of zidovudine outweighed the benefits of delaying disease progression. Clearly, neither extreme accurately reflects the correct approach for every patient.

Because of their uncertain effect on the quality of life, we specifically excluded laboratory findings, including metabolic abnormalities, from our quality-adjusted survival analysis and only considered severe symptomatic adverse events. Although the incidence of severe symptomatic adverse events in the group given 500 mg of zidovudine was not significantly higher than that in the placebo group (Table 1 of our article), the patients receiving the drug experienced these events sooner and therefore spent more time with the reduced quality of life associated with such events (Table 2 of our article).

The delay of the progression of HIV disease produced by the use of zidovudine (500 mg daily) in patients with asymptomatic HIV infection who have fewer than 500 CD4+ cells per cubic millimeter is real but of limited magnitude, and this benefit must be weighed against the costs associated with the toxicity of the therapy. We thank Berman and Wenglin for the opportunity to reemphasize the true conclusion of our study: patients' preferences concerning the effects of adverse events on their quality of life should be taken into account when their physicians are considering zidovudine therapy for asymptomatic HIV infection.

William R. Lenderking, Ph.D.
Richard D. Gelber, Ph.D.
Deborah J. Cotton, M.D., M.P.H.
Harvard School of Public Health, Boston, MA 02115

1 References

1. 1

   Gelber RD, Lenderking WR, Cotton DJ, et al. Quality-of-life evaluation in a clinical trial of zidovudine therapy in patients with mildly symptomatic Hiv infection. Ann Intern Med 1992;116:961-966
   Web of Science | Medline