A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection : results of the Veterans Affairs Cooperative Study

• Published in: The New England journal of medicine Vol. 326; no. 7; pp. 437 - 443
• Main Authors: HAMILTON, J. D, HARTIGAN, P. M, HAWKES, C. A, JENSEN, P. C, KLIMAS, N. G, LABRIOLA, A. M, LAHART, C. J, O'BRIEN, W. A, OSYTER, C. N, WEINHOLD, K. J, WRAY, N. P, ZOLLA-PAZNER, S. B, SIMBERKOFF, M. S, DAY, P. L, DIAMOND, G. R, DICKINSON, G. M, DRUSANO, G. L, EGORIN, M. J, GEORGE, W. L, GORDIN, F. M
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 13-02-1992
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CD4-Positive T-Lymphocytes; Double-Blind Method; Female; Follow-Up Studies; HIV Infections - drug therapy; HIV Infections - mortality; human immunodeficiency virus; Humans; Leukocyte Count; Male; Medical sciences; Patient Compliance; Pharmacology. Drug treatments; Survival Rate; Time Factors; Zidovudine - administration & dosage; Zidovudine - adverse effects; Human; Late; Retroviridae; Controlled therapeutic trial; AIDS; Infection; Virus; Chemotherapy; Treatment; Viral disease; T-Lymphocyte; Lentivirinae; Antiviral; Early; Human immunodeficiency virus
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM199202133260703

Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established.
We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed.
During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash.
In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.