Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy.
Patients with HIV infection manifest increased T lymphocyte apoptosis. This study investigated the influence of antiretroviral therapy (ART) upon lymphocyte apoptosis in 23 HIV-infected adults naive to protease inhibitors. Patients were enrolled in a treatment trial consisting of Nelfinavir (NFV), d4T, or NFV + d4T for 24 weeks, followed by triple therapy (NFV + reverse transcriptase inhibitors) for an additional 24 weeks. Spontaneous T cell apoptosis in cultured PBMC decreased by 23.67 +/- 18.2% (P < 0.006) at 48 weeks and plasma HIV RNA decreased by 1.79 +/- 0.59 log(10) RNA copies/ml (P < 0.001). The absolute decrease and slope of T cell apoptosis correlated with plasma virus load and with activated CD8 T cells and was inversely correlated with CD4 T cells. We conclude that reduction in chronic antigenic stimulation and the absence of cellular signals elicited by viral products contribute to the rescue of T lymphocytes from apoptosis, which facilitates immunologic recovery in ART-treated patients.
Chavan
S J
SJ
Department of Pediatrics, NYU School of Medicine, Manhasset, New York, 11030, USA.
Tamma
S L
SL
Kaplan
M
M
Gersten
M
M
Pahwa
S G
SG
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000473:pathology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000502:physiology; D019888:Nelfinavir / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012190:Retroviridae / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors; D019562:Viral Load
D000998:Antiviral Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017320:HIV Protease Inhibitors; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D019888:Nelfinavir