Expansion of pre-terminally differentiated CD8 T cells in chronic HIV-positive patients presenting a rapid viral rebound during structured treatment interruption.
OBJECTIVE
The influence of structured treatment interruption on effector/memory CD8 T cell dynamics was analysed in chronic HIV-infected patients showing a rapid or delayed viral rebound.


METHODS
Structured treatment interruption consisted of at least one month of discontinuation, followed by highly active antiretroviral therapy (HAART) resumption. Two groups of HIV structured treatment interruption patients were selected on the basis of plasma viral HIV-RNA value (> 30 000 copies/ml, branched DNA): group A (n = 14), patients with a rapid viral rebound (within one month) and group B (n = 6), patients with a delayed or no viral rebound (after a minimum of 4 months).


METHODS
A clinical and immunological follow-up was performed at HAART suspension (t 0), one month from suspension (t 1), at HAART resumption (t 2), and 30 days from resumption (t 3).


RESULTS
A sustained viral rebound was observed in group A patients, showing a rapid expansion of circulating CD8 T lymphocytes. In this group, the frequencies of CD8 T cells releasing IFN-gamma after mitogen-induced or Gag-specific stimulation were highly increased after HAART discontinuation. Nevertheless, these CD8 T lymphocytes were mainly composed of pre-terminally differentiated cytotoxic T lymphocytes (CTL) expressing a CCR7 CD27 CD45RA phenotype and a reduced amount of perforin. In contrast, group B patients showed no significant changes in immunological parameters during a prolonged drug-free period.


CONCLUSIONS
These data indicate that monitoring CD8 T cell dynamics during structured treatment interruption could be clinically relevant, and new therapeutic strategies should aim qualitatively to restore CTL effector functions.
D'Offizi
Gianpiero
G
Laboratory of Immunopathology Padiglione Del Vecchio, National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
Montesano
Carla
C
Agrati
Chiara
C
Gioia
Cristiana
C
Amicosante
Massimo
M
Topino
Simone
S
Narciso
Pasquale
P
Pucillo
Leopoldo Paolo
LP
Ippolito
Giuseppe
G
Poccia
Fabrizio
F
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002472:Cell Transformation, Viral; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019562:Viral Load