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

John A. Bartlett, MD; Sharon L. Benoit, RN, MPH; Victoria A. Johnson, MD; Joseph B. Quinn, MSPH; Gladys E. Sepulveda, MD; W. Christopher Ehmann, MD; Chris Tsoukas, MD; Mary Ann Fallon, BSN; Pamela L. Self, MT; and Marc Rubin, MD
[+] Article and Author Information

For the North American HIV Working Party* From Duke University Medical Center, Durham, North Carolina; Glaxo Wellcome, Inc., Research Triangle Park, North Carolina; University of Alabama at Birmingham School of Medicine and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama; Hospital Regionale de Ponce, Ponce, Puerto Rico; Hershey Medical Center, Hershey, Pennsylvania; and McGill University, Montreal, Quebec, Canada. Acknowledgments: The authors thank all individual study site personnel, all at Glaxo Wellcome (Judy Johnson, Joseph Cowan, Carolyn Kaczka, Sharon Hill Price, Ricki Zameck, Debra Dawson, Bonnie Pobiner, Carol Gilbert, Jane Scott-Lennox, Ralph Demasi, Paul Jarrett, Geoff Yuen, Jim Esinhart, and Gary Pakes); Bruce McCreedy, PhD, and Kusum Mistry at Laboratory Corporation of America (formerly Roche Biomedical Laboratories, Research Triangle Park, North Carolina, and Raritan, New Jersey); Suzanne F. Wagner, C. Brian Overbay, Jeffrey R. Wagner, Byron Lambert, and D, Adam Plier, who helped process whole-blood clinical specimens from patients in the virology subset for planned drug resistance studies (University of Alabama at Birmingham School of Medicine, Birmingham, Alabama); Gary Pakes, PharmD, for assistance in manuscript preparation; and all of the study participants. Requests for Reprints: John A. Bartlett, MD, Box 3238, Duke University Medical Center, Durham, NC 27710. Current Author Addresses: Dr. Bartlett: Box 3238, Duke University Medical Center, Durham, NC 27710.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1996;125(3):161-172. doi:10.7326/0003-4819-125-3-199608010-00001
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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 plus 42.5 cells/mm3 in the low-dose lamivudine group, plus 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.

*For members of the North American HIV Working Party, see the Appendix.

Figures

Grahic Jump Location
Figure 1. The number of patients in each treatment group listed under each time point is the number of patients evaluated at that time. The zalcitabine group received 0.75 mg of zalcitabine plus zidovudine; the low-dose lamivudine group received 150 mg of lamivudine plus zidovudine; and the high-dose lamivudine group received 300 mg of lamivudine plus zidovudine.
Mean change (± SE) from baseline for absolute CD4+ cell counts (cells/mm3) by week of study.
Grahic Jump Location
Grahic Jump Location
Figure 2. The number of patients in each treatment group listed under each time point is the number of patients evaluated at that time. The zalcitabine group received 0.75 mg of zalcitabine plus zidovudine; the low-dose lamivudine group received 150 mg of lamivudine plus zidovudine; and the high-dose lamivudine group received 300 mg of lamivudine plus zidovudine.
Median change from baseline with 25 to 75th quartile range for log10 plasma human immunodeficiency virus (HIV) RNA by week of study.
Grahic Jump Location

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