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Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised e vidence

1999; Elsevier BV; Volume: 353; Issue: 9169 Linguagem: Inglês

10.1016/s0140-6736(98)12263-8

1474-547X

Donald I. Abrams, David Allan, Francisco Antunes, AM Breckenridge, Johan N. Bruun, D. William Cameron, C Carbon, Ian Chalmers, Hsin‐An Chang, J Chodakewitz, N Clendenin, Nathan Clumeck, Ann C. Collier, Gary Collins, Eugene R. Cooper, David A. Cooper, S. A. Danner, Richard T. D’Aquila, DeGruttola, Ralph DeMasi, Linda Dee, Lawrence Deyton, Dennis O. Dixon, Charles Farthing, J Feinberg, Margaret A. Fischl, Markus Flepp, Martin Gartland, Josep M. Gatell, B Gazzard, Frank D. Goebel, P. C Gotzsche, A. Gringeri, D. B. Hall, John D. Hamilton, S. Hammer, Pamela Hartigan, Margo Heath‐Chiozzi, Keith Henry, Andrew Hill, Bernard Hirschel, John P. A. Ioannidis, Jeffrey Kahn, Christine Katlama, David Katzenstein, John Paul Killen, Elizabeth King, SK de Loes, Stephen Kravcik, J Lange, Randi Y. Leavitt, John M. Leonard, A Mæland, P.M. Mannucci, L Mathiesen, Hugh McDade, A Meibohn, Hans Melander, T. C. Merigan, John Mulder, Maureen Myers, James D. Neaton, Michelle Neßling, Luc Perrin, C B Pettinelli, John Phair, Andrew Phillips, A J Pinching, A Poppa, Lawrence Power, Philip T. Reiss, D. D. Richman, James F. Rooney, Franck Rousseau, G. W. Rutherford, Miklos Salgo, Eric Sandström, Louis D. Saravolatz, G.F. Savidge, S M Schnittman, Robert T. Schooley, M Séligmann, Michael S. Simberkoff, Gail Skowron, Peter Slade, Danielle M. Smith, RP Smith, Vincent Soriano, K. Stanley, Georg Stingl, Paul Stoffels, Lesley Struthers, C. Tierney, Melanie Thompson, R Van der Broeck, R Van Leeuven, GJ Weverling, Jan A. Veenstra, Stefano Vella, Paul Volberding, Jan Weber, Dean L. Winslow, P. Yéni, Jie Ming Yeo, J Dormont, Merle A. Sande, I V Weller, Abdel Babiker, Rebecca Collins, J. Darbyshire, W. Raymond Duncan, Mary A. Foulkes, Mike Hughes, Richard Peto, Tea Peto, Sarah Walker, Hiv Trialists' Collaborative,

HIV/AIDS Research and Interventions

Summary Background To assess the effects of zidovudine, didanosine, and zalcitabine on HIV disease progression and survival, we undertook meta-analyses of individual patient data and tabular data from all randomised trials that compared these agents. Methods Individual patient data were available for 7722 participants without AIDS in the nine randomised trials of immediate versus deferred zidovudine, and 7700 participants with or without AIDS in the six trials comparing zidovudine plus didanosine, zidovudine plus zalcitabine, or zidovudine alone. The main outcomes were mortality and disease progression (new AIDS-defining event or death before any such event). Flndings In the comparison of immediate versus deferred zidovudine, during a median follow-up of 50 months, 1908 individuals progressed, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was zidovudine monotherapy in 94%). During the first year of follow-up, immediate zidovudine halved the rate of disease progression (p Interpretation Although immediate use of zidovudine halved disease progression during the first year, this effect was not sustained, and there was no improvement in survival in the short or long term. However, the use of didanosine and, to a lesser extent, zalcitabine delayed both disease progression and death, at least when added to zidovudine. The comparative effects of these different nucleoside analogues on long-term survival should inform the choice of which to combine with other types of drug, such as protease inhibitors.