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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 33; no. 3; pp. 380 - 386
• Main Authors: Thiébaut, Rodolphe, Chêne, Geneviève, Jacqmin-Gadda, Hélène, Morlat, Philippe, Mercié, Patrick, Dupon, Michel, Neau, Didier, Ramaroson, Hanta, Dabis, François, Salamon, Roger
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-07-2003; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; AIDS/HIV; Antiretroviral Therapy, Highly Active; Biological and medical sciences; Biomarkers - blood; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cohort Studies; Disease Progression; Drug therapy; Female; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human viral diseases; Humans; Immunology; Infectious diseases; Male; Medical sciences; Ribonucleic acid; RNA; RNA, Viral - blood; T cell receptors; Time Factors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Disease development; Immunopathology; Prognosis; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Numeration; Viral disease; T-Lymphocyte; Antiviral; Human immunodeficiency virus; Viral load
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/00126334-200307010-00013

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 adoptedfirst, 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/mm lower, P < 10) 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.