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

Abhay H. Patki, Scott F. Purvis, Hernan Valdez, John Spritzler, Elizabeth Connick, Daniel R. Kuritzkes, Harold Kessler, Lawrence Fox, Marty St Clair, Alan Landay, Michael M. Lederman

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To examine the DNA content of circulating lymphocytes obtained from HIV-1-infected persons and to explore the effects of antiretroviral therapy on these indices. Design: Cross-sectional analysis and 48-week open label treatment trial (AIDS Clinical Trials Group Protocol 315) of zidovudine, lamivudine and ritonavir. Methods: Peripheral blood lymphocytes were obtained from HIV-1-infected patients and healthy controls and after 48 h of in vitro cultivation were stained with propidium iodide and analyzed for DNA content by flow cytometry. Results: HIV-1-infected patients had more hypodiploid cells (19%), fewer G0-G1 phase cells (70%) and more S phase cells (10%) than did healthy controls (8%, 85% and 5% respectively; P = 0.002). Patients with sustained suppression of plasma HIV-1 RNA levels after antiretroviral therapy had only modest improvements in these indices. In contrast, patients who failed to suppress plasma HIV-1 RNA levels had decreases in G0-G1 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 correlation between the percentage of G0-G1 cells and expression of the activation antigens CD38 and HLA-DR on CD4 cells (r, -0.409; P = 0.016) and CD8 cells (r, -0.363; P = 0.035). Conclusions: Lymphocytes obtained from HIV-1-infected patients display perturbations in DNA content after brief cultivation in vitro reflective of immune activation in vivo. The marginal improvement in these indices after 'successful' suppression of HIV-1 replication suggests that even low levels of HIV-1 replication are sufficient to induce immune activation and perturbations in DNA content.

Original languageEnglish (US)
Pages (from-to)1177-1185
Number of pages9
JournalAIDS
Volume13
Issue number10
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Antiretroviral therapy
  • Apoptosis
  • Cell cycle
  • DNA synthesis
  • HIV-1 infection
  • Peripheral blood lymphocytes
  • Protease inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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