No evidence for proliferation in the blood CD4+ T-cell pool during HIV-1 infection and triple combination therapy.

ABSTRACT

OBJECTIVE: To evaluate the role of cell proliferation in peripheral blood lymphocyte (PBL) dynamics during HIV infection and potent antiretroviral therapy including protease inhibitors. DESIGN: Transverse study of 150 patients at different stages of infection. Longitudinal study of 50 patients on triple combination antiretroviral therapy with 9-month follow-up. METHODS: Ex vivo incubation of fresh PBL with the DNA biosynthetic marker bromodeoxyuridine (BrdU). Flow cytometric analysis of cell phenotypes and BrdU incorporation. Parallel determination of plasma virus load and CD4+ cell counts. RESULTS: Percentages of BrdU+ B and T lymphocytes found in patients with asymptomatic HIV infection were not different from the low values found in HIV-seronegative controls, and were not correlated with the CD4+ cell count. DNA synthesis increased significantly only during acute opportunistic infections occurring in patients with high plasma viral load and fewer than 100 x 10(6) CD4+ cells/l. Triple combination therapy induced a decrease of plasma virus load and a rise of CD4+ cell counts, whereas BrdU incorporation remained low or decreased. CONCLUSION: Proliferation of peripheral blood T cells observed at late stages of HIV infection corresponds to a response to opportunistic infections. Apart from these particular cases, proliferation in this compartment does not appear as a critical parameter of CD4+ cell kinetics during chronic HIV infection and potent therapy.