A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter

New England Journal of Medicine

Volumn 335, Issue 15, 1996, Pages 1081-1090

  Hammer, Scott M ^a,j   Katzenstein, David A ^b   Hughes, Michael D ^c   Gundacker, Holly ^c   Schooley, Robert T ^d   Haubrich, Richard H ^e   Henry, W Keith ^f   Lederman, Michael M ^g   Phair, John P ^h   Niu, Manette ⁱ   Hirsch, Martin S ^a   Merigan, Thomas C ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b STANFORD UNIVERSITY   (United States)

^c HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^d UNIVERSITY OF COLORADO   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF MINNESOTA   (United States)

^g CASE WESTERN RESERVE UNIVERSITY   (United States)

^h NORTHWESTERN UNIVERSITY   (United States)

ⁱ NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^j BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; DIDANOSINE; NUCLEOSIDE; PLACEBO; ZALCITABINE; ZIDOVUDINE;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE COURSE; DOUBLE BLIND PROCEDURE; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SURVIVAL;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ADULT; ANTIVIRAL AGENTS; CD4 LYMPHOCYTE COUNT; DIDANOSINE; DISEASE PROGRESSION; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HIV INFECTIONS; HUMANS; MALE; PROPORTIONAL HAZARDS MODELS; TREATMENT OUTCOME; ZIDOVUDINE;

EID: 10144244674     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM199610103351501     Document Type: Article

References (45)

1. Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: a double-blind, placebo-controlled trial. N Engl J Med 1987;317: 185-91.
2. Volberding PA, Lagakos SW, Koch MA, et al. Zidovudine in asymptomatic human immunodeficiency virus infection: a controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N Engl J Med 1990;322:941-9.
3. Fischl MA, Richman DD, Hansen N, et al. 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. Ann Intern Med 1990;112:727-37.
4. Hamilton JD, Hartigan PM, Simberkoff MS, et al. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection: results of the Veterans Affairs Cooperative Study. N Engl J Med 1992;326:437-43.
5. Cooper DA, Gatell JM, Kroon S, et al. Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. N Engl J Med 1993;329:297-303.
6. Concorde Coordinating Committee. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 1994;343:871-81.
7. Volberding PA, Lagakos SW, Grimes JM, et al. The duration of zidovudine benefit in persons with asymptomatic HIV infection: prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group. JAMA 1994; 272:437-42.
8. Volberding PA, Lagakos SW, Grimes JM, et al. A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. N Engl J Med 1995;333:401-7.
9. Caliendo AM, Hirsch MS. Combination therapy for infection due to human immunodeficiency virus type 1. Clin Infect Dis 1994;18:516-24. [Erratum, Clin Infect Dis 1994;19:379.]
10. Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 1995;373:117-22.
11. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995;373:123-6.
12. Meng TC, Fischl MA, Boota AM, et al. Combination therapy with zidovudine and dideoxycytidine in patients with advanced human immunodeficiency virus infection: a phase I/II study. Ann Intern Med 1992;116: 13-20.
13. Collier AC, Coombs RW, Fischl MA, et al. Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection. Ann Intern Med 1993;119:786-93.
14. Yarchoan R, Lietzau JA, Nguyen BY, et al. A randomized pilot study of alternating or simultaneous zidovudine and didanosine therapy in patients with symptomatic human immunodeficiency virus infection. J Infect Dis 1994;169:9-17.
15. Collier AC, Coombs RW, Schoenfeld DA, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. N Engl J Med 1996;334:1011-7.
16. D'Aquila RT, Hughes MD, Johnson VA, et al. Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;124:1019-30.
17. Gulick R, Mellors J, Havlir D, et al. Potent and sustained antiretroviral activity of indinavir, zidovudine and lamivudine. In: Abstracts of the 11th International Conference on AIDS program supplement, Vancouver, B.C., July 7-12, 1996:19. abstract.
18. Fischl MA, Stanley K, Collier AC, et al. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. Ann Intern Med 1995;122:24-32.
19. Division of AIDS table for grading severity of adult adverse experiences. Rockville, Md.: National Institute of Allergy and Infectious Diseases, 1996.
20. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly Rep 1987;36:Suppl 1S:3S-14S.
21. Lan KKG, DeMets DL. Discrete sequential boundaries of clinical trials. Biometrika 1983;70:659-63.
22. O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549-56.
23. Hughes MD. Stopping guidelines for clinical trials with multiple treatments. Stat Med 1993;12:901-15.
24. Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: John Wiley, 1980.
25. Pocock SJ. Clinical trials: a practical approach. Chichester, England: John Wiley, 1983.
26. Armitage P. Statistical methods in medical research. Oxford, England: Blackwell Scientific, 1971.
27. The Delta Coordinating Committee. Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet 1996;348:283-91.
28. Eron JJ, Benoit SL, Jemsek J, et al. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N Engl J Med 1995;333:1662-9.
29. Staszewski S, Loveday C, Picazo JJ, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients: a randomized controlled comparison with zidovudine monotherapy. JAMA 1996;276:111-7.
30. Bartlett JA, Benoit SL, Johnson VA, et al. Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;125:161-72.
31. Larder BA, Kemp SD, Harrigan PR. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 1995; 269:696-9.
32. Katlama C, Ingrand D, Loveday C, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients: a randomized controlled comparison with zidovudine monotherapy. JAMA 1996;276:118-25.
33. 3. In: Abstracts of the 11th International Conference on AIDS, Vancouver, B.C., July 7-12, 1996:22. abstract.
34. Massari F, Staszewski S, Berry P, et al. A double-blind randomized trial of indinavir alone or with zidovudine vs. zidovudine alone in zidovudine naive patients. In: Program and abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy: program addendum, San Francisco, September 17-20, 1995. Washington, D.C.: American Society for Microbiology, 1995:9. abstract.
35. Rey D, Pi T, Diehl LJ, Hughes M, Merigan TC, Katzenstein DA. Do plasma codon 215 mutations explain the failure of ZDV in ACTG 175? In: Fifth International Workshop on HIV Drug Resistance, Whistler, B.C., July 3-6, 1996:38, abstract.
36. Saravolatz LD, Winslow DL, Collins G, et al. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. N Engl J Med 1996;335:1099-106.
37. Dolin R, Amato DA, Fischl MA, et al. Zidovudine compared with didanosine in patients with advanced HIV type 1 infection and little or no previous experience with zidovudine. Arch Intern Med 1995;155:961-74. [Erratum, Arch Intern Med 1995;155:2255.]
38. Baker CJ, Englund J, Raskino C, McKinney R, Fowler M, ACTG 152 Study Team. Comparison of zidovudine (ZDV), didanosine (ddI), or combination ZDV/ddI therapy in symptomatic, HIV-infected children (ACTG 152). In: Abstracts of the 11th International Conference on AIDS program supplement, Vancouver, B.C., July 7-12, 1996:12. abstract.
39. Pavia AT, Gathe J, Grosso R, et al. Clinical efficacy of stavudine compared to zidovudine in ZDV-pretreated HIV-positive patients. In: Program and abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 17-20, 1995. Washington, D.C.: American Society for Microbiology, 1995:235. abstract.
40. Kitchen VS, Skinner C, Ariyoshi K, et al. Safety and activity of saquinavir in HIV infection. Lancet 1995;345:952-5.
41. Schapiro JM, Winters MA, Stewart F, et al. The effect of high-dose saquinavir on viral load and CD4+ T-cell counts in HIV-infected patients. Ann Intern Med 1996;124:1039-50.
42. Danner SA, Carr A, Leonard JM, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. N Engl J Med 1995;333:1528-33.
43. Condra JH, Schleif WA, Blahy OM, et al. In vitro emergence of HIV-I variants resistant to multiple protease inhibitors. Nature 1995;374:569-71.
44. Markowitz, M, Saag M, Powderly WG, et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med 1995;333:1534-9.
45. Cameron DW, Heath-Chiozzi M, Kravcik S, et al. Prolongation of life and prevention of AIDS complications in advanced HIV immunodeficiency with ritonavir: update. In: Abstracts of the 11th International Conference on AIDS, Vancouver, B.C., July 7-12, 1996:24. abstract.