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Changes of lymphocyte apoptosis associated with sequential introduction of highly active antiretroviral therapy
Author(s) -
Wasmuth JC,
Hackbarth F,
Rockstroh JK,
Sauerbruch T,
Spengler U
Publication year - 2003
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1046/j.1468-1293.2003.00145.x
Subject(s) - cd38 , medicine , apoptosis , cd8 , annexin , fas receptor , immunology , indinavir , ex vivo , annexin a5 , amprenavir , surrogate endpoint , virology , in vivo , viral load , antiretroviral therapy , human immunodeficiency virus (hiv) , programmed cell death , biology , protease , immune system , microbiology and biotechnology , hiv 1 protease , flow cytometry , stem cell , cd34 , enzyme , biochemistry
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. Conclusion 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.