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 from HIV-1-infected persons and to explore the effects of antiretroviral therapy on these indices.


METHODS
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.
Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106, USA.
A H
AH
Patki
S F
SF
Purvis
H
H
Valdez
J
J
Spritzler
E
E
Connick
D R
DR
Kuritzkes
H
H
Kessler
L
L
Fox
M
M
St Clair
A
A
Landay
M M
MM
Lederman
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002453:Cell Cycle; D003430:Cross-Sectional Studies; D004247:DNA / Q000378:metabolism*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism* / Q000502:physiology; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D004247:DNA; D019438:Ritonavir