The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection a double-blind, placebo-controlled trial

Margaret A. Fischl, Douglas D. Richman, Nellie Hansen, Ann C. Collier, John T. Carey, Michael F. Para, W. David Hardy, Raphael Dolin, William G. Powderly, J. Davis Allan, Brian Wong, Thomas C. Merigan, Vincent J. McAuliffe, Newton E. Hyslop, Frank S. Rhame, Henry H. Balfour, Stephen A. Spector, Paul Volberding, Carla Pettinelli, James Anderson

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Abstract

Objective: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. Design: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. Setting: Multicenter trial at AIDS Clinical Trials units. Subjects: Seven hundred eleven subjects with mildly symptomatic HIV infection. Intervention: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. Measurements and Main Results: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. Conclusion: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

Original languageEnglish (US)
Pages (from-to)727-737
Number of pages11
JournalAnnals of Internal Medicine
Volume112
Issue number10
StatePublished - May 15 1990
Externally publishedYes

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Zidovudine
Virus Diseases
HIV-1
Placebos
T-Lymphocytes
Safety
Acquired Immunodeficiency Syndrome
CD4 Lymphocyte Count
Therapeutics
Candidiasis
Neutropenia
Multicenter Studies
Anemia
Randomized Controlled Trials
Clinical Trials
Antigens
Serum

ASJC Scopus subject areas

  • Medicine(all)

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The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection a double-blind, placebo-controlled trial. / Fischl, Margaret A.; Richman, Douglas D.; Hansen, Nellie; Collier, Ann C.; Carey, John T.; Para, Michael F.; Hardy, W. David; Dolin, Raphael; Powderly, William G.; Allan, J. Davis; Wong, Brian; Merigan, Thomas C.; McAuliffe, Vincent J.; Hyslop, Newton E.; Rhame, Frank S.; Balfour, Henry H.; Spector, Stephen A.; Volberding, Paul; Pettinelli, Carla; Anderson, James.

In: Annals of Internal Medicine, Vol. 112, No. 10, 15.05.1990, p. 727-737.

Research output: Contribution to journalArticle

Fischl, MA, Richman, DD, Hansen, N, Collier, AC, Carey, JT, Para, MF, Hardy, WD, Dolin, R, Powderly, WG, Allan, JD, Wong, B, Merigan, TC, McAuliffe, VJ, Hyslop, NE, Rhame, FS, Balfour, HH, Spector, SA, Volberding, P, Pettinelli, C & Anderson, J 1990, 'The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection a double-blind, placebo-controlled trial', Annals of Internal Medicine, vol. 112, no. 10, pp. 727-737.
Fischl, Margaret A. ; Richman, Douglas D. ; Hansen, Nellie ; Collier, Ann C. ; Carey, John T. ; Para, Michael F. ; Hardy, W. David ; Dolin, Raphael ; Powderly, William G. ; Allan, J. Davis ; Wong, Brian ; Merigan, Thomas C. ; McAuliffe, Vincent J. ; Hyslop, Newton E. ; Rhame, Frank S. ; Balfour, Henry H. ; Spector, Stephen A. ; Volberding, Paul ; Pettinelli, Carla ; Anderson, James. / The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection a double-blind, placebo-controlled trial. In: Annals of Internal Medicine. 1990 ; Vol. 112, No. 10. pp. 727-737.
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abstract = "Objective: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. Design: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. Setting: Multicenter trial at AIDS Clinical Trials units. Subjects: Seven hundred eleven subjects with mildly symptomatic HIV infection. Intervention: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. Measurements and Main Results: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95{\%} CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95{\%} CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95{\%} CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5{\%} and 4{\%} of zidovudine recipients, respectively, and in 0{\%} and 1{\%} of placebo recipients, respectively. Conclusion: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.",
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T1 - The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection a double-blind, placebo-controlled trial

AU - Fischl, Margaret A.

AU - Richman, Douglas D.

AU - Hansen, Nellie

AU - Collier, Ann C.

AU - Carey, John T.

AU - Para, Michael F.

AU - Hardy, W. David

AU - Dolin, Raphael

AU - Powderly, William G.

AU - Allan, J. Davis

AU - Wong, Brian

AU - Merigan, Thomas C.

AU - McAuliffe, Vincent J.

AU - Hyslop, Newton E.

AU - Rhame, Frank S.

AU - Balfour, Henry H.

AU - Spector, Stephen A.

AU - Volberding, Paul

AU - Pettinelli, Carla

AU - Anderson, James

PY - 1990/5/15

Y1 - 1990/5/15

N2 - Objective: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. Design: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. Setting: Multicenter trial at AIDS Clinical Trials units. Subjects: Seven hundred eleven subjects with mildly symptomatic HIV infection. Intervention: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. Measurements and Main Results: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. Conclusion: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

AB - Objective: To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection. Design: A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts. Setting: Multicenter trial at AIDS Clinical Trials units. Subjects: Seven hundred eleven subjects with mildly symptomatic HIV infection. Intervention: Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months. Measurements and Main Results: Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively. Conclusion: Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.

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