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Therapeutics

Benefits of zidovudine were balanced by quality-of-life reductions in HIV infection

ACP J Club. 1994 Sept-Oct;121:33. doi:10.7326/ACPJC-1994-121-2-033


Source Citation

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. Mar


Abstract

Objective

To determine, from a quality-of-life perspective, the effect of zidovudine treatment on asymptomatic patients infected with human immunodeficiency virus (HIV).

Design

Retrospective analysis of an 18-month randomized, double-blind, placebo-controlled trial.

Setting

{32 participating university-affiliated tertiary care institutions of the AIDS Clinical Trial Group.} (Data from Volberding PA, et al. N Engl J Med. 1990;332:941-9.)

Patients

{1434 patients with HIV infection who were ≥ 18 years of age (92% men 91% white) and had CD4+ cell counts < 500/µL. Patients with pre-existing symptomatic HIV disease and those with previously limited tolerance to zidovudine were excluded. 1338 (93%) enrolled patients were included in the analysis.} (Data from Volberding.)

Intervention

{Patients were stratified by CD4+ cell count (< 200/µL or 200 to 499/µL) and were randomized to either zidovudine, 100 mg 5 times/d (n = 453); zidovudine, 300 mg 5 times/d (n = 457); or placebo (n = 428).} (Data from Volberding.)

Main Outcome Measures

Disease progression consisted of the first occurrence of the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death. Adverse events were identified and graded from records of laboratory findings and symptoms; they consisted of the first occurrence of severe events (grades 3 and 4). The entire time after the first occurrence of an adverse event was considered to be part of that adverse experience. A threshold utility analysis incorporated weighted data that reflected the relative qualities of life associated with disease progression and with adverse events.

Main Results

Compared with the placebo group, the group receiving 500 mg of zidovudine gained time (a mean of 0.5 months) without HIV disease progression but had a severe symptomatic adverse event earlier (a mean of 0.6 months earlier). Patients receiving 500 mg of zidovudine had a better quality of life than did patients receiving placebo but only when survival time after disease progression was considered less desirable than survival time after a severe symptomatic adverse event.

Conclusion

Among asymptomatic patients with human immunodeficiency virus infection who were treated with 500 mg of zidovudine per day for 18 months, the gains in quality of life from delayed progression of disease were approximately offset by the losses in quality of life caused by the earlier onset of the adverse consequences of therapy.

Source of funding: National Institute of Allergy and Infectious Diseases; American Cancer Society; Agency for Health Care Policy and Research.

For article reprint: Dr. W.R. Lenderking, Department of Biostatistics, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115. FAX 617-432-2832.


Commentary

The authors are to be commended for comparing the quality of life of asymptomatic patients treated with placebo or zidovudine with the time until disease progression.

Because of data limitations, this analysis is provocative but not definitive. The quality of life was not measured but, instead, inferred from symptoms. The analytic method Q-TWiST (the quality-of-life-adjusted survival relative to TWiST [the time without symptoms of disease or toxicity]) depends heavily on utility weighted data. The authors did not measure this weighted data but showed all outcomes based on the full range of possible weighted data. Lastly, their analytic decision to count the occurrence of any symptom as perpetually lowering the quality of life probably biased the study against zidovudine treatment. Surely some of these symptoms were transient and would probably have had a minimal effect on the quality of life.

Still, the underlying message is clear: For studies comparing treatments for patients with chronic diseases, such as AIDS, in whom benefits in mortality are probably slim, an appropriate end point for comparing therapies is the patient's quality of life. This cannot be assessed by the physician without asking the patient. Until better data become available, physicians should consider asking each patient what he or she values more: a short (but probably real) delay in time until progression of HIV disease or a greater likelihood of side effects from the medication. Different patients may choose different treatment options. Clinicians who deal with patients with other chronic diseases (and the researchers who study them) would be wise to learn the lessons of this study: Quality of life is an important patient outcome. Be sure to measure it in research and ask about it when you see patients.

Paul G. Shekelle, MD, PhD
West Los Angeles Veterans Affairs Medical Center Santa Monica, California, USA