In patients on prolonged HAART, a significant pool of HIV infected CD4 T cells are HIV-specific.
OBJECTIVE
To examine the antigen specificities of HIV reservoir CD4 T cells in patients on prolonged and effective highly active antiretroviral therapy (HAART).


METHODS
Five HIV-infected patients, who were highly adherent to antiretroviral treatment, were selected on the basis of long-term undetectable plasma viral RNA on unmodified HAART. To investigate the antigen specificities of infected memory CD4 T cells, we examined the capacity of recall antigens, including HIV antigens, to induce virus production by peripheral blood mononuclear cells (PBMC).


METHODS
To quantify CD4 T cells infected by replication-competent virus, and to determine their antigen specificities, we used a limiting dilution-based culture assay. CD8 T cell-depleted PBMC at several cell densities were activated by using Tuberculin purified protein derivative, cytomegalovirus, or HIV-1 p24 with and without HIV-1 Nef.


RESULTS
We found that the pool of infected CD4 T cells includes HIV-specific cells with apparent frequencies between 5- and 100-fold higher than those of the common specificities for cytomegalovirus or Tuberculin.


CONCLUSIONS
Our findings suggest that a significant proportion of replication-competent HIV-infected CD4 T cells in these patients are memory cells directed against HIV determinants. This may provide a rationale for the therapeutic use of recombinant HIV antigens to reduce the pool of HIV-reservoir cells.
Demoustier
Audrey
A
INSERM E-0109, Faculté de Médecine de Bicêtre, Université Paris-XI, Bicêtre, France.
Gubler
Brigitte
B
Lambotte
Olivier
O
de Goër
Marie-Ghislaine
MG
Wallon
Christine
C
Goujard
Cécile
C
Delfraissy
Jean-François
JF
Taoufik
Yassine
Y
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D013997:Time Factors; D017735:Virus Latency; D014779:Virus Replication
D015488:HIV Antigens