7 research outputs found
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The Efficacy of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex
We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by
Pneumocystis carinii
pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo.
When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P<0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P<0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P<0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not among AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P<0.001).
These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS–related complex, at least over the 8 to 24 weeks of observation in this study. (N Engl J Med 1987; 317:185–91.)
THE acquired immunodeficiency syndrome (AIDS) is characterized by severe immunodeficiency, life-threatening opportunistic infections, neoplasia, and a fatal outcome. The underlying immune defect in AIDS is caused by infection with a human retrovirus — human immunodeficiency virus (HIV), formerly called human T-cell lymphotropic virus Type III/lymphadenopathy-associated virus.
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In addition, infection with this virus frequently causes a debilitating condition known as the AIDS-related complex. Strategies for the treatment of patients with AIDS or AIDS-related complex have focused on the development of drugs with activity against HIV in vitro and on agents that may restore immunity.
Azidothymidine (3′-azido-3′-deoxythymidine; zidovudine [Retrovir], or AZT) is . .
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Prolonged Zidovudine Therapy in Patients With AIDS and Advanced AIDS-Related Complex
We examined the long-term safety and efficacy of zidovudine therapy in 229 subjects with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex who previously participated in a placebo-controlled study of zidovudine. One hundred two placebo recipients (delayed treatment group) and 127 zidovudine recipients (original treatment group) were followed up while receiving zidovudine therapy for a mean of 21 months. Survival rates for the original treatment group were 84.5% and 57.6% at 12 and 21 months, respectively; for the delayed treatment group, 78.8% and 64.6% at 12 and 18 months, respectively; and 78.8% and 47.5% at 12 and 21 months, respectively, for 77 subjects with AIDS and 93.0% and 71.8%, respectively, for 50 subjects with AIDS-related complex in the original treatment group. Adverse reactions decreased over time and newly observed toxic reactions were unusual. The clinical course of these subjects suggests continued survival benefits with long-term zidovudine therapy.(JAMA. 1989;262:2405-2410
Design and in Vitro Evaluation of Zidovudine Oral Controlled Release Tablets Prepared Using Hydroxypropyl Methylcellulose
Impaired ability of bone marrow cells from immunodeficient mice to establish long-term cultures
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The Duration of Zidovudine Benefit in Persons With Asymptomatic HIV Infection: Prolonged Evaluation of Protocol 019 of the AIDS Clinical Trials Group
Objective.—To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4+ cell count.Design and Interventions.—Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo.Setting.—University-based and university-affiliated AIDS research clinics participating in AIDS Clinical Trials Group protocol 019.Patients.—A total of 1565 asymptomatic HIV-infected subjects with entry CD4+ cell counts less than 0.50×109/L (500/μL).Main Outcome Measure.—Time to progression to AIDS or death.Results.—During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P=.008,.004,.007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P=.002,.08,.04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4+ cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo.Conclusions.—Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished over time especially in subjects with entry CD4+ cell counts less than 0.30×109/L (300/μL). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored.(JAMA. 1994;272:437-442