Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users

Carbone, Javiera; Gil, Juanaa; Benito, José M.a; Navarro, Joaquína; Muñóz-Fernández, Angelesa; Bartolomé, Joaquína; Zabay, José M.a; López, Franciscob; Fernández-Cruz, Eduardoa

AIDS:
Basic Science
Abstract

Objective: To identify subsets of CD4 T lymphocytes that can predict the development of AIDS and to assess whether increased levels of these cellular markers could provide additional independent prognostic information to the CD4 T cell count and plasma HIV-1-RNA levels.

Design and methods: In a prospective study, a cohort of 85 HIV-positive intravenous drug users [clinical categories of the CDC classification A (n = 48) and B (n = 37)] were followed for a period of 37 ± 13 months. Memory and activated CD4 and CD8 T cells were quantitated by three-colour flow cytometry at baseline and expressed as a percentage of total CD4 and CD8 lymphocytes. Clinical evaluations were performed at 6 month intervals. The relationships between these lymphocyte subsets and progression to AIDS were studied using Kaplan–Meier plots and proportional hazards regression models.

Results: After adjustment for the level of CD4 T cells and plasma HIV-1-RNA levels, the elevation in the subset CD4+CD38+DR+ was the marker within the functionally distinct subsets of CD4 T lymphocytes with additional prognostic value in bivariate Cox regression models. In multivariate models, increased percentages of CD4+CD38+DR+ T cells provided the strongest independent prognostic information for progression to AIDS (relative hazard, 1.07;P < 0.0001).

Conclusion: Our results suggest that high levels of CD4+CD38+HLA-DR+ T cells reflect the increasing degree of CD4 T cell activation during the progression of HIV infection, and could be used together with the CD4 T cell and HIV-RNA levels to evaluate more accurately the progressive cellular immune impairment associated with the risk of progression to AIDS.

Author Information

From the aDepartment of Immunology, University General Hospital Gregorio Marañón, Complutense University, Madrid, Spain; and bNufarm-21 Madrid, Spain.

Correspondence and reprint requests to: Dr Javier Carbone, Department of Immunology, University General Hospital Gregorio Marañón, Dr Esquerdo, 46, 28007 Madrid, Spain. Tel: +34 91 5868423; fax: +34 91 5866698; e-mail: carbone@teleline.es

Received: 23 August 1999;

revised: 22 August 2000; accepted: 26 September 2000.

Sponsorship: This study was supported by grants from the ‘Comunidad Autónoma de Madrid’ and the ‘Fondo de Investigación Sanitaria’ to E.F.-C.

© 2000 Lippincott Williams & Wilkins, Inc.