Objectives: To examine the antigen specificities of HIV reservoir CD4 T cells in patients on prolonged and effective highly active antiretroviral therapy (HAART).
Design: 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.
Conclusion: 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.
From the aINSERM E-0109, Faculté de Médecine de Bicêtre, Université Paris-XI, Bicêtre, the bLaboratory of Immunology and the cDepartment of Internal Medicine, Bicetre Hospital, Bicêtre, France.
Correspondence to Y Taoufik, INSERM E-0109, Faculté de Médecine de Bicêtre, Université Paris-XI, 63 Rue Gabriel Péri, 94276 Bicêtre, France.
Note: B. Gubler and O. Lambotte contributed equally to this work.
Note: This work was presented in part at the First IAS conference on HIV pathogenesis and AIDS. Buenos Aires, Argentina. July 2001 [abstract 21, Session 4. Oral, Viral Reservoirs].
Received: 30 November 2001;
revised: 19 April 2002; accepted: 28 May 2002.
Sponsorship: This work was supported by grants from Agence Pour La Recherche Contre Le Sida (ANRS), SIDACTION-Fondation pour la Recherche Médicale and INSERM.