Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.
CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or proapoptotic markers in cultured PBMCs and T lymphocytes. The significant relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery suggests that persistent apoptosis may impede immune restoration.
Hansjee
Natasha
N
Institute for Medical Microbiology, University of Basel, Division of Infectious Diseases, Department of Internal Medicine, University Hospital Basel, Switzerland.
Kaufmann
Gilbert R
GR
Strub
Christoph
C
Weber
Rainer
R
Battegay
Manuel
M
Erb
Peter
P
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014779:Virus Replication / Q000187:drug effects