Persistent immune activation in HIV-1 infection is associated with progression to AIDS.
BACKGROUND
HIV-1 infection is characterized by chronic generalized CD8 and CD4 T cell hyperactivation, the biological effect of which is not understood.


OBJECTIVE
To study the relation between chronic immune activation and CD4 T cell depletion in HIV-1 infection.


METHODS
Prospective cohort study among participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who have a known seroconversion date (n = 102).


METHODS
CD4 and CD8 T cell activation marker expression was analysed by FACScan before and after seroconversion (1 and 5 years after seroconversion); T cell proliferation and T cell numbers were also measured. Cox proportional hazard analyses were used to study the predictive value of these parameters for progression to AIDS.


RESULTS
Preseroconversion low CD4 T cell numbers or elevated levels of CD4 T cell activation were associated with increased risk for development of AIDS after HIV-1 seroconversion. Progression to AIDS was associated with loss of both CD4 and CD8 naive T cells. The predictive value of CD8 T cell activation was confirmed and, in addition, in the course of infection low CD4 T cell counts and increasing proportions of dividing CD4 T cells, dividing CD8 T cells or elevated CD4 T cell activation marker expression became independent predictors of progression to AIDS.


CONCLUSIONS
Increased T cell activation has predictive value for HIV-1 disease progression even before seroconversion. These data support the hypothesis that persistent hyperactivation of the immune system may lead to erosion of the naive T cell pool and CD4 T cell depletion.
Hazenberg
Mette D
MD
Department of Clinical Viro-Immunology, Sanquin Research at CLB, Tropical Medicine and AIDS, Amsterdam, The Netherlands.
Otto
Sigrid A
SA
van Benthem
Birgit H B
BH
Roos
Marijke Th L
MT
Coutinho
Roel A
RA
Lange
Joep M A
JM
Hamann
Dörte
D
Prins
Maria
M
Miedema
Frank
F
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018450:Disease Progression; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1; D006801:Humans; D019394:Ki-67 Antigen / Q000097:blood; D008213:Lymphocyte Activation; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood
D019394:Ki-67 Antigen; D012367:RNA, Viral