Many HIV-infected CD4 cells are HIV-specific in patients on HAART

Among HIV-infected patients receiving prolonged highly active antiretroviral therapy (HAART), a substantial proportion of replication-competent HIV-infected CD4 T cells are memory cells directed against HIV determinants, French researchers report.

They suggest that this reservoir of cells might be targeted for elimination using recombinant HIV antigens.

Dr. Yassine Taoufik from Universite Paris, Bic tre, and colleagues studied five HIV-positive patients who were highly adherent to an unmodified HAART regimen and had long-term undetectable HIV levels.

Using a limited dilution-based culture assay, the researchers examined CD4 memory cells infected with replication-competent HIV from these patients to determine their antigen specificities.

They looked at the ability of recall antigens, including Tuberculin purified protein derivative, cytomegalovirus, and HIV-1 p24 with and without HIV-1 Nef, to induce virus production by peripheral blood mononuclear cells (PBMC) depleted of CD8 T cells, according to their report in the 6 September issue of AIDS.

Dr. Taoufik’s team found that the number of HIV-specific cells in the pool of infected CD4 T cells was five to 100 times more than the number of cells with specificities for cytomegalovirus or tuberculin.

They conclude that “altogether, our results show that HIV antigens can induce marked HIV replication by latently infected cells from patients on prolonged HAART.”

Dr. Taoufik and colleagues add that this finding “may provide a rationale for the use of recombinant HIV antigens to activate latently infected cells and thereby to reduce this reservoir, as it is likely that infected cells die following virus activation, while HAART inhibits new cell formation. Specific immunotherapy based on recombinant HIV antigens might have fewer adverse effects than cytokine therapy. “