Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: a meta-analysis. HIV Surrogate Marker Collaborative Group.
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.
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D019562:Viral Load
D012367:RNA, Viral