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.
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.


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).


CONCLUSIONS
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.
Carbone
J
J
Department of Immunology, University General Hospital Gregorio Marañón, Complutense University, Madrid, Spain. carbone@teleline.es
Gil
J
J
Benito
J M
JM
Navarro
J
J
Muñóz-Fernández
A
A
Bartolomé
J
J
Zabay
J M
JM
López
F
F
Fernández-Cruz
E
E
D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D015819:Substance Abuse, Intravenous / Q000150:complications* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D012367:RNA, Viral