Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: A meta-analysis

A. Babiker, J. Bartlett, A. Breckenridge, G. Collins, R. Coombs, D. Cooper, T. Creagh, A. Cross, M. Daniels, J. Darbyshire, D. Dawson, V. DeGruttola, R. DeMasi, R. Dolin, J. Eron, M. Fischl, S. Grossberg, J. Hamilton, S. Hammer, P. HartiganK. Henry, A. Hill, M. Hughes, J. Kahn, C. Katlama, D. Katzenstein, S. Kim, D. Mildvan, J. Montaner, M. Moore, J. Neaton, W. O'Brien, H. Ribaudo, D. Richman, M. Saag, M. Salgo, L. Saravolatz, R. Schooley, M. Seligmann, S. Staszewski, L. Struthers, C. Tierney, A. Tsiatis, S. Welles, M. D. Hughes

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Objective: To evaluate treatment-mediated changes in HIV-1 RNA and CD4 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 CD4 count determinations at 24 weeks after starting treatment. Results: At Week 24, the percentage of subjects experiencing an HIV-1 RNA decrease of >1 log10 copies/ml or a CD4 count increase of >33% was similar (22% vs 25%). Changes in both markers at Week 24 were significant independent predictors of AIDS/death: Across trials, the average reduction in hazard was 51% per 1 log10 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 CD4 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.

Original languageEnglish
Pages (from-to)1123-1133
Number of pages11
JournalAIDS Research and Human Retroviruses
Issue number12
StatePublished - 10 Aug 2000
Externally publishedYes


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