Reduction of viral load and immune complex load on CD4+ lymphocytes as a consequence of highly active antiretroviral treatment (HAART) in HIV-infected hemophilia patients.
OBJECTIVE
Human immunodeficiency virus (HIV)-induced immune complex load on circulating CD4+ blood lymphocytes is associated with dysfunction and depletion of CD4+ lymphocytes and with increased monocyte/macrophage function. It was investigated whether HAART reduces both the viral load in plasma and the number of immune complex-coated CD4+ lymphocytes in the blood, and whether CD4+ counts are associated with viral load and/or immune complex load.


METHODS
Twelve HIV+ hemophilia patients before and after conversion to HAART (group 1); eight HIV+ hemophilia patients without antiretroviral therapy (group 2). HIV-1 RNA copies in plasma using NASBA/Nuclisens kits; CD4+ lymphocytes coated in-vivo with immune complexes using flowcytometry on whole blood samples; in-vitro responses of immune complex-coated T lymphocytes in cell culture assays.


RESULTS
After conversion to HAART there was a significant reduction of viral load, CD4+ gp120+, CD4+ IgM+, and CD4+ IgG+ circulating blood lymphocytes and plasma neopterin, paralleled by a significant increase of CD4+ and CD8+ counts. The percentage of immune complex-coated CD4+ lymphocytes of converted patients was significantly associated with CD4+ counts, in-vitro responses to concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), anti-CD3 and pooled allogeneic stimulator cells, and with plasma neopterin levels.


CONCLUSIONS
HAART reduces viral load and HIV-induced immune complex load on circulating CD4+ blood lymphocytes. The results of this study can be interpreted to suggest that HAART increases CD4+ lymphocyte counts in part by counteracting HIV-induced autoimmune phenomena.
Daniel
V
V
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Germany. volker_daniel@med.uni-heidelberg.de
Süsal
C
C
Melk
A
A
Weimer
R
R
Kröpelin
M
M
Zimmermann
R
R
Huth-Kühne
A
A
Uhle
C
C
Opelz
G
G
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003208:Concanavalin A / Q000494:pharmacology; D004359:Drug Therapy, Combination; D015699:HIV Envelope Protein gp120 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000276:immunology
D019380:Anti-HIV Agents; D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; D007136:Immunoglobulins; D008934:Mitogens; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003208:Concanavalin A