Changes of lymphocyte apoptosis associated with sequential introduction of highly active antiretroviral therapy.
OBJECTIVE
To assess the effect of highly active antiretroviral therapy (HAART) on surrogate markers of lymphocyte apoptosis in HIV 1-infected individuals.


METHODS
Ex vivo apoptosis was studied prospectively in 26 antiretroviral naive HIV-positive patients up to 12 weeks after sequential initiation of HAART [phase I: nucleoside reverse transcriptase inhibitor (NRTI), phase II: NRTI + protease inhibitor (PI)]. Apoptosis was assessed via CD95-, Apo2.7-expression and annexin-V-binding in peripheral CD4, CD8, B and NK-cells, and compared to changes in activation markers (HLA-DR, CD38) and viral loads.


RESULTS
After introduction of HAART CD4-counts rose significantly mainly through cell redistribution, while activation markers decreased. Although Apo2.7 expression decreased throughout the study period, it was not possible to establish a correlation to the rise in CD4 cells. Unexpectedly, CD95 expression and annexin V binding were elevated during phase I of treatment without PI and began to decline only after the addition of a PI in phase II. Poor responders to antiretroviral therapy had significantly higher CD95 expression and annexin V binding in the initial phase of antiretroviral regimen.


CONCLUSIONS
These data show divergent effects of HAART on surrogate markers of apoptosis, when treatment is initiated sequentially with NRTIs first. Partial suppression of HIV replication during treatment without PI may be associated with increased rates of apoptosis.
Wasmuth
J-C
JC
Department of Internal Medicine I, University of Bonn, Germany. j-c.wasmuth@uni-bonn.de
Hackbarth
F
F
Rockstroh
J K
JK
Sauerbruch
T
T
Spengler
U
U
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D018709:Statistics, Nonparametric; D019562:Viral Load; D019014:fas Receptor / Q000097:blood
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019014:fas Receptor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1