HIV infection perturbs DNA content of lymphoid cells: partial correction after 'suppression' of virus replication

Objective: To examine the DNA content of circulating lymphocytes obtained f rom HIV-1-infected persons and to explore the effects of antiretroviral the rapy on these indices. Design: Cross-sectional analysis and 48-week open label treatment trial (AI DS Clinical Trials Group Protocol 315) of zidovudine, lamivudine and ritona vir. Methods: Peripheral blood lymphocytes were obtained from HIV-1-infected pat ients and healthy controls and after 48 h of in vitro cultivation were stai ned with propidium iodide and analyzed for DNA content by flow cytometry. Results: HIV-1-infected patients had more hypodiploid cells (19%), fewer G( 0)-G(1) phase cells (70%) and more S phase cells (10%) than did healthy con trols (8%, 85% and 5% respectively; P = 0.002). Patients with sustained sup pression of plasma HIV-1 RNA levels after antiretroviral therapy had only m odest improvements in these indices. In contrast, patients who failed to su ppress plasma HIV-1 RNA levels had decreases in G(0)-G(1) cells to 54% (P = 0.032) and increases in S phase cells to 24% (P = 0.055). Plasma HIV-1 RNA levels and the percentage of S phase cells were correlated (r, 0.23; P = 0 .047). In patients failing antiretroviral therapy, there was an inverse cor relation between the percentage of G(0)-G(1) cells and expression of the ac tivation antigens CD38 and HLA-DR on CD4 cells (r, -0.409; P = 0.016) and C D8 cells (r, -0.363; P = 0.035). Conclusions: Lymphocytes obtained From HIV-1-infected patients display pert urbations in DNA content after brief cultivation in vitro reflective of imm une activation in vivo. The marginal improvement in these indices after 'su ccessful' suppression of HIV-1 replication suggests that even low levels of HIV-1 replication are sufficient to induce immune activation and perturbat ions in DNA content. (C) 1999 Lippincott Williams & Wilkins.