Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial

Daniel R. Kuritzkes, Ian Marschner, Victoria A. Johnson, Roland Bassett, Joseph J. Eron, Margaret A. Fischl, Robert L. Murphy, Kenneth Fife, Janine Maenza, Mary E. Rosandich, Dawn Bell, Ken Wood, Jean Pierre Sommadossi, Caria Pettinelli

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Objective: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). Design: Randomized, placebo-controlled, partially double-blinded multicenter study. Setting: Adult AIDS Clinical Trials Units. Patients: Treatment-naive HIV-infected adults with 200-600 x 106 CD4 T lymphocytes/l. Interventions: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. Main outcome measure: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. Results: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log10 (d4T monotherapy) versus 1.03 log10 (d4T plus 3TC; P = 0.001), and 0.68 log10 (ddl monotherapy) versus 0.82 log10 (ddl plus 3TC; P > 0.22). After 48 weeks the mean reduction was 1.08 log10 (d4T plus 3TC) versus 1.01 log10 (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log10 (ddl plus 3TC) versus 0.88 log10 (ZDV plus 3TC; P = 0.70) in the ddl limb. Conclusions: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4T as a component of initial combination antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)685-694
Number of pages10
JournalAIDS
Volume13
Issue number6
DOIs
StatePublished - Jul 1 1999

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Keywords

  • Antiretroviral therapy
  • Combination therapy
  • HIV
  • Lamivudine
  • Stavudine
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kuritzkes, D. R., Marschner, I., Johnson, V. A., Bassett, R., Eron, J. J., Fischl, M. A., Murphy, R. L., Fife, K., Maenza, J., Rosandich, M. E., Bell, D., Wood, K., Sommadossi, J. P., & Pettinelli, C. (1999). Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. AIDS, 13(6), 685-694. https://doi.org/10.1097/00002030-199904160-00009