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

• Published in: AIDS research and human retroviruses Vol. 16; no. 12; p. 1123
• Format: Journal Article
• Language: English
• Published: United States 10.08.2000
• Subjects: Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - physiopathology; CD4 Lymphocyte Count; HIV Infections - blood; HIV Infections - immunology; HIV Infections - physiopathology; HIV-1 - genetics; HIV-1 - isolation & purification; Humans; Prognosis; Randomized Controlled Trials as Topic; RNA, Viral - blood; Viral Load
• ISSN: 0889-2229
• DOI: 10.1089/088922200414965

To evaluate treatment-mediated changes in HIV-1 RNA and CD4 count as prognostic markers and surrogate end points for disease progression (AIDS/death). 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. 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. 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.