BACKGROUND: Persistent low CD4(+) cell counts are observed in 5%-27% of patients treated for human immunodeficiency virus (HIV)-1 infection despite their having prolonged undetectable plasma viral loads. METHODS: To understand the possible mechanisms of this discordant immunological situation, a prospective transsectional case-control study was designed. HIV-1-infected subjects who had a plasma viral load <200 copies/mL for >1 year were considered to be case patients if their CD4(+) cell count was <250/mm(3); control patients had CD4(+) cell counts >500/mm(3) and were matched by sex, age, and nadir CD4(+) cell count to case patients. T cell proliferation after stimulation with various antigens, T cell subset counts, T cell rearrangement excision circles (TRECs), T cells undergoing apoptosis, cytokines influencing apoptosis, and cellular proviral DNA and plasma viral RNA persistence were assessed. RESULTS: Compared with the 19 control patients, the 19 case patients had undistinguishable lymphoproliferative responses to candidin and cytomegalovirus, fewer naive CD4(+) cells (CD45RA(+)62L(+), 23%+/-13% vs. 47%+/-14%; P<.0001), lower thymic output (1.28 vs. 3.95 TRECs/microL of blood; P=.0015), increased cell death by apoptosis (spontaneous, 23.2%+/-8.3% vs. 11.9%+/-8.4% [P=.02]; Fas induced, 38.6%+/-13.7% vs. 16.4%+/-8.0% [P=.004]), higher levels of plasma soluble tumor necrosis factor receptor II (9.6 vs. 5.3 ng/mL; P=.0058), and undistinguishable plasma HIV-1 and cellular proviral DNA loads. CONCLUSIONS: The mechanisms responsible for the low-level regeneration of CD4(+) cells involve, at least, deficiency in the regeneration of central CD4(+) cells and excessive apoptosis.
BACKGROUND: Persistent low CD4(+) cell counts are observed in 5%-27% of patients treated for human immunodeficiency virus (HIV)-1 infection despite their having prolonged undetectable plasma viral loads. METHODS: To understand the possible mechanisms of this discordant immunological situation, a prospective transsectional case-control study was designed. HIV-1-infected subjects who had a plasma viral load <200 copies/mL for >1 year were considered to be case patients if their CD4(+) cell count was <250/mm(3); control patients had CD4(+) cell counts >500/mm(3) and were matched by sex, age, and nadir CD4(+) cell count to case patients. T cell proliferation after stimulation with various antigens, T cell subset counts, T cell rearrangement excision circles (TRECs), T cells undergoing apoptosis, cytokines influencing apoptosis, and cellular proviral DNA and plasma viral RNA persistence were assessed. RESULTS: Compared with the 19 control patients, the 19 case patients had undistinguishable lymphoproliferative responses to candidin and cytomegalovirus, fewer naive CD4(+) cells (CD45RA(+)62L(+), 23%+/-13% vs. 47%+/-14%; P<.0001), lower thymic output (1.28 vs. 3.95 TRECs/microL of blood; P=.0015), increased cell death by apoptosis (spontaneous, 23.2%+/-8.3% vs. 11.9%+/-8.4% [P=.02]; Fas induced, 38.6%+/-13.7% vs. 16.4%+/-8.0% [P=.004]), higher levels of plasma soluble tumor necrosis factor receptor II (9.6 vs. 5.3 ng/mL; P=.0058), and undistinguishable plasma HIV-1 and cellular proviral DNA loads. CONCLUSIONS: The mechanisms responsible for the low-level regeneration of CD4(+) cells involve, at least, deficiency in the regeneration of central CD4(+) cells and excessive apoptosis.
Authors: Richard M Dunham; Ivan Vujkovic-Cvijin; Steven A Yukl; Mara J Broadhurst; Pʼng Loke; Rebecca G Albright; Joseph K Wong; Michael M Lederman; Ma Somsouk; Peter W Hunt; Jeffrey N Martin; Steven G Deeks; Joseph M McCune Journal: J Acquir Immune Defic Syndr Date: 2014-02-01 Impact factor: 3.731
Authors: Timothy J Wilkin; Christina M Lalama; John McKinnon; Rajesh T Gandhi; Nina Lin; Alan Landay; Heather Ribaudo; Lawrence Fox; Judith S Currier; John W Mellors; Roy Gulick; Allan R Tenorio Journal: J Infect Dis Date: 2012-06-27 Impact factor: 5.226
Authors: Michael M Lederman; Leonard Calabrese; Nicholas T Funderburg; Brian Clagett; Kathy Medvik; Hector Bonilla; Barbara Gripshover; Robert A Salata; Alan Taege; Michelle Lisgaris; Grace A McComsey; Elizabeth Kirchner; Jane Baum; Carey Shive; Robert Asaad; Robert C Kalayjian; Scott F Sieg; Benigno Rodriguez Journal: J Infect Dis Date: 2011-10-15 Impact factor: 5.226
Authors: Michael M Lederman; Nicholas T Funderburg; Rafick P Sekaly; Nichole R Klatt; Peter W Hunt Journal: Adv Immunol Date: 2013 Impact factor: 3.543
Authors: B O Taiwo; X Li; F Palella; L P Jacobson; J B Margolick; R Detels; C R Rinaldo; J P Phair Journal: HIV Med Date: 2009-07-09 Impact factor: 3.180
Authors: Lyle R McKinnon; Makobu Kimani; Charles Wachihi; Nico J Nagelkerke; Festus K Muriuki; Anthony Kariri; Richard T Lester; Lawrence Gelmon; T Blake Ball; Francis A Plummer; Rupert Kaul; Joshua Kimani Journal: PLoS One Date: 2010-07-02 Impact factor: 3.240