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

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Abstract
To evaluate the role of cell proliferation in peripheral blood lymphocyte (PBL) dynamics during HIV infection and potent antiretroviral therapy including protease inhibitors. 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. 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. 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 × 106 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. 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.