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. 2010 Feb 23;7(2):e1000239.
doi: 10.1371/journal.pmed.1000239.

Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies

Marcel Wolbers  1 , Abdel Babiker, Caroline Sabin, Jim Young, Maria Dorrucci, Geneviève Chêne, Cristina Mussini, Kholoud Porter, Heiner C Bucher; CASCADE Collaboration Members
Collaborators, Affiliations

Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies

Marcel Wolbers et al. PLoS Med. .

Abstract

Background: CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART.

Methods and findings: We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46-81) cells/microl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97-1.04) for each 10 cells/microl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/microl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94-1.03, for each 10 cells/microl per year reduction in CD4 cell decline).

Conclusions: The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/microl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients. Please see later in the article for the Editors' Summary.

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Conflict of interest statement

HCB received travel grants, honoraria, and unrestricted research grants from various pharmaceutical companies including, GlaxoSmithKline, Bristol-Myers-Squibb, Gilead, Roche, Abbott, Tibotec, and Boehringer-Ingelheim. The research of MW, JY, and HCB is supported by unrestricted grants from santésuisse and the Gottfried and Julia Bangerter-Rhyner-Foundation. The Medical Research Council, Clinical Trials HIV Group, led by AB, received donated drugs and/or financial support for substudies from the following pharmaceutical companies: Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Cipla, Gilead, Tibotec, Roche, GlaxoSmithKline, Indevus, Merck, Novartis, Sanofi Pasteur, and Virco. KP also received honorarium from Tibotec. CS has received funding for research, teaching, and consultancy from several pharmaceutical companies (GlaxoSmithKline, Gilead Sciences, Bristol-Myers Squibb, and Tibotec) over the last few years. CM received travel grants and honoraria from: GlaxoSmithKline, Bristol-Myers-Squibb, Gilead, Roche, Abbott, Tibotec, and Boehringer-Ingelheim. The research of CM is supported by Istituto Superiore di Sanità.

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