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Time-Updated CD4+ T Lymphocyte Count and HIV RNA as Major Markers of Disease Progression in Naive HIV-1-Infected Patients Treated With a Highly Active Antiretroviral Therapy: The Aquitaine Cohort, 1996-2001

Thiébaut Rodolphe; Chêne, Geneviève; Jacqmin-Gadda, Hélène; Morlat, Philippe; Mercié, Patrick; Dupon, Michel; Neau, Didier; Ramaroson, Hanta; Dabis, François; Salamon, Roger; the Groupe d’Epidémiologic Clinique du SIDA en Aquitaine (GECSA)
JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2003

In naive HIV-1 infected patients who start a highly active antiretroviral therapy (HAART), the relationship between time-updated CD4+ cell count, HIV RNA, and clinical progression (new AIDS-defining event or death) is incompletely understood. A 2-step statistical approach was adopted: first, modeling the evolution of the 2 markers taking into account left-censoring of HIV RNA and, second, studying their respective effect on clinical progression. The study sample consisted in 551 previously untreated patients of the Aquitaine Cohort who started their first HAART regimen between 1996 and 2000. During a median follow-up of 33 months, 46 patients experienced a new AIDS-defining diagnosis and 23 died. In multivariate survival analysis, time-updated CD4+ cell count (hazard ratio [HR] = 1,92 for 100 cells/mm3 lower, P < 10-4) and HIV RNA (HR = 1.30 for 1 log10 copies/mL higher, P = 0.04) on continuous scale were associated with clinical progression. When analyzing the effect of updated biomarkers using usual thresholds, the association with clinical progression was weaker for CD4+ but still significant (P = 0.007) whereas it remained only significant for updated HIV RNA above 4 log10 copies/mL (P = 0.01). The prognostic information of updated HIV RNA adjusted on updated CD4+ is significant but depends on how the markers are taken into account. Clinical decisions and interpretation of clinical trial results must weigh the signification of each of these 2 biomarkers.

The Groupe d’Epidémiologie Clinique du SIDA en Aquitaine (GECSA) overseeing the Aquitaine Cohort is organized as follows: Scientific committee: Prs. J. Beylot, M. Dupon, M. Le Bras, J. L. Pellegrin, J. M. Ragnaud, and R. Salamon (Chair); Scientific coordination: Prs. F. Dabis and G. Chêne; Medical coordination: Drs. N. Bernard, D. Lacoste, D. Malvy, P. Mercié, D. Neau, Prs. M. Dupon, J-F. Moreau, P. Morlat, J. L. Pellegrin, and J. M. Ragnaud; Statistical analysis: D. Commenges, H. Jacqmin-Gadda, R. Thiébaut; Data management: Dr. S. Lawson-Ayayi, V. Lavignolle, E. Ballestre; Technical team: M. J. Blaizeau, M. Decoin, A. M. Formaggio, S. Delveaux, B. Uwamaliya, G. Palmer, D. Touchard, D. Dutoit, F. Pereira, and B. Boulant; Participating hospital departments (participating physicians): Bordeaux University Hospital: Pr. J. Beylot (Pr. P. Morlat, Drs. N. Bernard, F. Bonnet, D. Lacoste), Pr. C. Beylot (Pr. M.S. Doutre), Pr. C. Conri (Dr. J. Constans), Pr. P. Couzigou, Pr. H. Fleury (Drs. B. Masquelier, I. Pellegrin), Pr. M. Geniaux (Pr. A. Taieb, Mrs. A. Simon), Pr. JY. Lacut (Pr. M. Dupon, Dr. I. Chossat), Pr. J. L. Pellegrin (Dr. P. Mercie, Pr. B. Leng), Pr. M. LeBras (Drs F. Djossou, D. Malvy, and J. P. Pivetaud), Pr. J. F. Moreau (Dr. J. L. Taupin), Pr. J. M. Ragnaud (Drs. C. De La Taille, H. Dutronc, D. Neau), Pr. C. Series, Pr. A. Taytard; Dax Hospital: Dr. M. Loste (Dr. I. Blanchard); Bayonne Hospital: Drs. F. Bonnal and M. Ferrand (Drs. Y. Blanchard, S. Farbos, MC. Gemain); Libourne Hospital: Drs. J. Ceccaldi, B. Darpeix, and P. Legendre (Dr. X. Jacquelin); Villeneuve-sur-Lot Hospital: Drs. E. Buy and G. Brossard†


The Aquitaine Cohort is supported in part by a grant from the Agence Nationale de Recherches sur le SIDA (ANRS, Action Coordonnée no. 7, Cohortes). R. Thiébaut is supported by a fellowship from the Charity Ensemble Contre le SIDA (Sidaction).

Address correspondence and reprint requests to Pr. G. Chêne, ISPED, INSERM U330, Case 11 Université Victor Segalen, Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. E-mail:

Manuscript received March 1, 2002; accepted September 30, 2002.

© 2003 Lippincott Williams & Wilkins, Inc.