7th Conference - Abstract 136

HIV-1 Latent Reservoirs Renewed by Viral Replication in Activated CD4+ T Lymphocytes, Monocytes, and Resting CD4+ T Lymphocytes in Patients Receiving Potent Therapy

T. ZHU*, D. MUTHUI, S. HOLTE, Y. CHANG, D. NICKLE, F. FENG, T. SHEA, M. BERREY, S. BRODIE, S. SELF, J. MULLINS, and L. COREY. Univ. of Washington and Fred Hutchinson Cancer Res. Ctr., Seattle

Recent studies show in patients with prolonged suppression of plasma virus by highly active antiretroviral therapy (HAART) that HIV-1 persists latently in resting CD4+ T lymphocytes, which may, at least in part, result from on-going viral replication in vivo. It is unclear where and how the viral replication occurred. We present here the replication and genetic characteristics of HIV-1 in the peripheral blood activated CD4+ T lymphocytes, resting CD4+ T lymphocytes and monocytes from twelve acutely infected patients who have been on HAART for up to 4 years. HIV-1 proviruses persisted in the activated CD4+ T lymphocytes and monocytes-macrophages as well as resting CD4+ lymphocytes. The levels of HIV-1 DNA in monocytes were lower than that in both activated and resting CD4+ T cells during the period of studied. There was no significant difference in HIV-1 DNA levels between resting CD4+ T cells and activated CD4+ T cells. However, the levels of HIV-1 unspliced mRNA, gag, and multispliced mRNA, tat, were significantly higher in activate CD4+ T cells and monocytes than that in resting CD4+ T cells. In two out of seven patients, more HIV-1 sequence variation was observed in activated CD4+ T cells and monocytes compared to that in resting CD4+ T cells. The later variants that resulted from continued HIV-1 replication were most closely associated with the early variants in monocytes and activated CD4+ T cells. These findings suggest in patients with undetectable plasma virus due to HAART that HIV-1 produced in monocytes and activated CD4+ T cells seed HIV-1 latent reservoirs in the blood.

Key Words: Replication, Reservoirs, Therapy