Lamivudine Plus Zidovudine Compared with Zalcitabine Plus Zidovudine in Patients with HIV Infection: A Randomized, Double-Blind, Placebo-Controlled Trial

John A. Bartlett, Sharon L. Benoit, Victoria A. Johnson, Joseph B. Quinn, Gladys E. Sepulveda, W. Christopher Ehmann, Chris Tsoukas, Mary Ann Fallon, Pamela L. Self, Marc Rubin

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Abstract

Objective: To compare the safety and activity of lamivudine plus zidovudine with the safety and activity of zalcitabine plus zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received zidovudine. Design: A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. Setting: 21 sites in the United States, Canada, and Puerto Rico. Patients: 254 patients who had received zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm3. Interventions: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (low-dose lamivudine group); 300 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (high-dose lamivudine group); or 0.75 mg of zalcitabine plus 200 mg of zidovudine three times daily (zalcitabine group). Measurements: Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. Results: 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log10 copies/ml in the low-dose lamivudine group, -0.51 log10 copies/ml in the high-dose lamivudine group, and -0.39 log10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose lamivudine regimen appeared to be better tolerated than the others. Conclusions: In patients with HIV infection who had previously received zidovudine, 150 mg of lamivudine plus zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.

Original languageEnglish (US)
Pages (from-to)161-172
Number of pages12
JournalAnnals of internal medicine
Volume125
Issue number3
DOIs
StatePublished - Aug 1 1996

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Zalcitabine
Lamivudine
Zidovudine
Virus Diseases
Placebos
HIV
CD4 Lymphocyte Count
Safety
RNA
Puerto Rico
Therapeutics
Reverse Transcriptase Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Bartlett, John A. ; Benoit, Sharon L. ; Johnson, Victoria A. ; Quinn, Joseph B. ; Sepulveda, Gladys E. ; Ehmann, W. Christopher ; Tsoukas, Chris ; Fallon, Mary Ann ; Self, Pamela L. ; Rubin, Marc. / Lamivudine Plus Zidovudine Compared with Zalcitabine Plus Zidovudine in Patients with HIV Infection : A Randomized, Double-Blind, Placebo-Controlled Trial. In: Annals of internal medicine. 1996 ; Vol. 125, No. 3. pp. 161-172.
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abstract = "Objective: To compare the safety and activity of lamivudine plus zidovudine with the safety and activity of zalcitabine plus zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received zidovudine. Design: A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. Setting: 21 sites in the United States, Canada, and Puerto Rico. Patients: 254 patients who had received zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm3. Interventions: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (low-dose lamivudine group); 300 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (high-dose lamivudine group); or 0.75 mg of zalcitabine plus 200 mg of zidovudine three times daily (zalcitabine group). Measurements: Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. Results: 78{\%} of patients completed 24 weeks of study treatment, and 63{\%} of patients completed 52 weeks of study treatment. Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log10 copies/ml in the low-dose lamivudine group, -0.51 log10 copies/ml in the high-dose lamivudine group, and -0.39 log10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose lamivudine regimen appeared to be better tolerated than the others. Conclusions: In patients with HIV infection who had previously received zidovudine, 150 mg of lamivudine plus zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.",
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Lamivudine Plus Zidovudine Compared with Zalcitabine Plus Zidovudine in Patients with HIV Infection : A Randomized, Double-Blind, Placebo-Controlled Trial. / Bartlett, John A.; Benoit, Sharon L.; Johnson, Victoria A.; Quinn, Joseph B.; Sepulveda, Gladys E.; Ehmann, W. Christopher; Tsoukas, Chris; Fallon, Mary Ann; Self, Pamela L.; Rubin, Marc.

In: Annals of internal medicine, Vol. 125, No. 3, 01.08.1996, p. 161-172.

Research output: Contribution to journalArticle

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T1 - Lamivudine Plus Zidovudine Compared with Zalcitabine Plus Zidovudine in Patients with HIV Infection

T2 - A Randomized, Double-Blind, Placebo-Controlled Trial

AU - Bartlett, John A.

AU - Benoit, Sharon L.

AU - Johnson, Victoria A.

AU - Quinn, Joseph B.

AU - Sepulveda, Gladys E.

AU - Ehmann, W. Christopher

AU - Tsoukas, Chris

AU - Fallon, Mary Ann

AU - Self, Pamela L.

AU - Rubin, Marc

PY - 1996/8/1

Y1 - 1996/8/1

N2 - Objective: To compare the safety and activity of lamivudine plus zidovudine with the safety and activity of zalcitabine plus zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received zidovudine. Design: A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. Setting: 21 sites in the United States, Canada, and Puerto Rico. Patients: 254 patients who had received zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm3. Interventions: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (low-dose lamivudine group); 300 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (high-dose lamivudine group); or 0.75 mg of zalcitabine plus 200 mg of zidovudine three times daily (zalcitabine group). Measurements: Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. Results: 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log10 copies/ml in the low-dose lamivudine group, -0.51 log10 copies/ml in the high-dose lamivudine group, and -0.39 log10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose lamivudine regimen appeared to be better tolerated than the others. Conclusions: In patients with HIV infection who had previously received zidovudine, 150 mg of lamivudine plus zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.

AB - Objective: To compare the safety and activity of lamivudine plus zidovudine with the safety and activity of zalcitabine plus zidovudine in patients with moderately advanced human immunodeficiency virus (HIV) infection who had received zidovudine. Design: A multicenter, randomized, double-blind, three-arm, 24-week study with a blinded extension through at least 52 weeks. Setting: 21 sites in the United States, Canada, and Puerto Rico. Patients: 254 patients who had received zidovudine (median duration of previous therapy, 20 months) and had absolute CD4+ cell counts of 100 to 300 cells/mm3. Interventions: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (low-dose lamivudine group); 300 mg of lamivudine twice daily plus 200 mg of zidovudine three times daily (high-dose lamivudine group); or 0.75 mg of zalcitabine plus 200 mg of zidovudine three times daily (zalcitabine group). Measurements: Immunologic activity was assessed primarily by changes in absolute CD4+ cell counts; virologic activity was assessed by changes in plasma HIV RNA levels as measured by reverse transcriptase polymerase chain reaction. Safety of the treatment regimens was assessed through the reporting of adverse events. Results: 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log10 copies/ml in the low-dose lamivudine group, -0.51 log10 copies/ml in the high-dose lamivudine group, and -0.39 log10 copies/mL in the zalcitabine group). No significant differences in safety were seen among the three regimens, although the low-dose lamivudine regimen appeared to be better tolerated than the others. Conclusions: In patients with HIV infection who had previously received zidovudine, 150 mg of lamivudine plus zidovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.

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