Human Immunodeficiency Virus Type 1 RNA Level and CD4 Count as Prognostic Markers and Surrogate End Points: A Meta-Analysis
| Autor: | Schlomo Staszewski, Donna Mildvan, Julio S. G. Montaner, Heather R. Ribaudo, Robert T. Schooley, Raphael Dolin, Margaret A. Fischl, Camlin Tierney, John D. Hamilton, T. Creagh, Sunyoung Kim, M. Seligmann, Michael J. Daniels, Anastasios A. Tsiatis, David A. Cooper, David Katzenstein, Janet Darbyshire, Joseph J. Eron, Michael S. Saag, Abdel Babiker, James D. Neaton, A. Cross, Gary Collins, Christine Katlama, M. D. Hughes, Victor DeGruttola, Louis D. Saravolatz, Seth L. Welles, William A. O'Brien, Robert W. Coombs, Douglas D. Richman, Keith Henry, A. Breckenridge, Miklos Salgo, Pamela M. Hartigan, John Bartlett, Andrew M. Hill, Mark D. Moore, James G. Kahn, R.A. DeMasi, L. Struthers, Grossberg Se, Michael Hughes, D. Dawson, Scott M. Hammer |
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| Rok vydání: | 2000 |
| Předmět: |
Univariate analysis
medicine.medical_specialty Multivariate analysis business.industry Immunology Hazard ratio Area under the curve RNA Lamivudine Gastroenterology Confidence interval law.invention Infectious Diseases Randomized controlled trial law Virology Internal medicine medicine business medicine.drug |
| Zdroj: | AIDS Research and Human Retroviruses. 16:1123-1133 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/088922200414965 |
| Popis: | Objective: To evaluate treatment-mediated changes in HIV-1 RNA and CD3 count as prognostic markers and surrogate end points for disease progression (AIDS/death). Methods: Data from 13,045 subjects in all 16 randomized trials comparing nucleoside analogue reverse transcriptase inhibitors and having HIV-1 RNA measurements at 24 weeks were obtained. A total of 3146 subjects had HIV-1 RNA and CD3 count determinations at 24 weeks after starting treatment. Results: At Week 24, the percentage of subjects experiencing an HIV-1 RNA decrease of >1 log(10) copies/ml or a CD4 count increase of >33% was similar (22% vs 25%). Changes in both markers at Week 24 mere significant independent predictors of AIDS/death: across trials, the average reduction in hazard was 51% per 1 log(10) HIV-1 RNA copies/ml decrease (95% confidence interval: 41%, 59%) and 20% per 33% CD4 count increase (17%, 24%). In univariate analyses, the hazard ratio for AIDS/death in randomized treatment comparisons was significantly associated with differences between treatments in mean area under the curve of HIV-1 RNA changes to Weeks 8 and 24 (AUCMB) and mean CD3 change at Week 24, but, in multivariate analysis, only mean CD4 change was significant. Conclusions: Change in HIV-1 RNA, particularly using AUCMB, and in CD4 count should be measured to aid patient management and evaluation of treatment activity in clinical trials. However, short-term changes in these markers are imperfect as surrogate end points for long-term clinical outcome because two randomized treatment comparisons may show similar differences between treatments in marker changes but not similar differences in progression to AIDS/death. |
| Databáze: | OpenAIRE |
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