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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

Wolbers, M; Babiker, A; Sabin, C; Young, J; Dorrucci, M; Chene, G; Mussini, C; ... Bucher, HC; + view all (2010) 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. PLoS Medicine , 7 (2) , Article e1000239. 10.1371/journal.pmed.1000239. Green open access

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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-naive patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46-81) cells/mu l 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/mu l 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/mu l 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/mu l 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/mu l. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients.

Type: Article
Title: 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
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pmed.1000239
Publisher version: http://dx.doi.org/10.1371/journal.pmed.1000239
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: HIV-1-INFECTED PATIENTS, COUNTS, PROGNOSIS, MODEL, RNA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: http://discovery.ucl.ac.uk/id/eprint/111964
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