BACKGROUND: The extent to which immunologic and clinical biomarkers influence human immunodeficiency virus type 1 (HIV-1) infection outcomes remains incompletely characterized, particularly for non-B subtypes. On the basis of data supporting in vitro HIV-1 protein-specific CD8 T lymphocyte responses as correlates of immune control in cross-sectional studies, we assessed the relationship of these responses, along with established HIV-1 biomarkers, with rates of CD4 cell count decrease in individuals infected with HIV-1 subtype C. METHODS: Bivariate and multivariate mixed-effects models were used to assess the relationship of baseline CD4 cell count, plasma viral load, human leukocyte antigen (HLA) class I alleles, and HIV-1 protein-specific CD8 T cell responses with the rate of CD4 cell count decrease in a longitudinal population-based cohort of 300 therapy-naive, chronically infected adults with baseline CD4 cell counts >200 cells/mm(3) and plasma viral loads >500 copies/mL over a median of 25 months of follow-up. RESULTS: In bivariate analyses, baseline CD4 cell count, plasma viral load, and possession of a protective HLA allele correlated significantly with the rate of CD4 cell count decrease. No relationship was observed between HIV-1 protein-specific CD8 T cell responses and CD4 cell count decrease. Results from multivariate models incorporating baseline CD4 cell counts (201-350 vs >350 cells/mm(3)), plasma viral load (< or =100,000 vs >100,000 copies/mL), and HLA (protective vs not protective) yielded the ability to discriminate CD4 cell count decreases over a 10-fold range. The fastest decrease was observed among individuals with CD4 cell counts >350 cells/mm(3) and plasma viral loads >100,000 copies/mL with no protective HLA alleles (-59 cells/mm(3) per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm(3), plasma viral loads < or =100,000 copies/mL, and a protective HLA allele (-6 cells/mm(3) per year). CONCLUSIONS: The combination of plasma viral load and HLA class I type, but not in vitro HIV-1 protein-specific CD8 T cell responses, differentiates rates of CD4 cell count decrease in patients with chronic subtype-C infection better than either marker alone.
BACKGROUND: The extent to which immunologic and clinical biomarkers influence humanimmunodeficiency virus type 1 (HIV-1) infection outcomes remains incompletely characterized, particularly for non-B subtypes. On the basis of data supporting in vitro HIV-1 protein-specific CD8 T lymphocyte responses as correlates of immune control in cross-sectional studies, we assessed the relationship of these responses, along with established HIV-1 biomarkers, with rates of CD4 cell count decrease in individuals infected with HIV-1 subtype C. METHODS: Bivariate and multivariate mixed-effects models were used to assess the relationship of baseline CD4 cell count, plasma viral load, human leukocyte antigen (HLA) class I alleles, and HIV-1 protein-specific CD8 T cell responses with the rate of CD4 cell count decrease in a longitudinal population-based cohort of 300 therapy-naive, chronically infected adults with baseline CD4 cell counts >200 cells/mm(3) and plasma viral loads >500 copies/mL over a median of 25 months of follow-up. RESULTS: In bivariate analyses, baseline CD4 cell count, plasma viral load, and possession of a protective HLA allele correlated significantly with the rate of CD4 cell count decrease. No relationship was observed between HIV-1 protein-specific CD8 T cell responses and CD4 cell count decrease. Results from multivariate models incorporating baseline CD4 cell counts (201-350 vs >350 cells/mm(3)), plasma viral load (< or =100,000 vs >100,000 copies/mL), and HLA (protective vs not protective) yielded the ability to discriminate CD4 cell count decreases over a 10-fold range. The fastest decrease was observed among individuals with CD4 cell counts >350 cells/mm(3) and plasma viral loads >100,000 copies/mL with no protective HLA alleles (-59 cells/mm(3) per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm(3), plasma viral loads < or =100,000 copies/mL, and a protective HLA allele (-6 cells/mm(3) per year). CONCLUSIONS: The combination of plasma viral load and HLA class I type, but not in vitro HIV-1 protein-specific CD8 T cell responses, differentiates rates of CD4 cell count decrease in patients with chronic subtype-C infection better than either marker alone.
Authors: J W Mellors; A Muñoz; J V Giorgi; J B Margolick; C J Tassoni; P Gupta; L A Kingsley; J A Todd; A J Saah; R Detels; J P Phair; C R Rinaldo Journal: Ann Intern Med Date: 1997-06-15 Impact factor: 25.391
Authors: Nina D Russell; Michael G Hudgens; Richard Ha; Colin Havenar-Daughton; M Juliana McElrath Journal: J Infect Dis Date: 2003-01-06 Impact factor: 5.226
Authors: Beth D Jamieson; Otto O Yang; Lance Hultin; Mary Ann Hausner; Patricia Hultin; Jose Matud; Kevin Kunstman; Scott Killian; John Altman; Kristina Kommander; Bette Korber; Janis Giorgi; Steven Wolinsky Journal: J Immunol Date: 2003-11-15 Impact factor: 5.422
Authors: R A Kaslow; M Carrington; R Apple; L Park; A Muñoz; A J Saah; J J Goedert; C Winkler; S J O'Brien; C Rinaldo; R Detels; W Blattner; J Phair; H Erlich; D L Mann Journal: Nat Med Date: 1996-04 Impact factor: 53.440
Authors: M Dean; M Carrington; C Winkler; G A Huttley; M W Smith; R Allikmets; J J Goedert; S P Buchbinder; E Vittinghoff; E Gomperts; S Donfield; D Vlahov; R Kaslow; A Saah; C Rinaldo; R Detels; S J O'Brien Journal: Science Date: 1996-09-27 Impact factor: 47.728
Authors: Y Rivière; M B McChesney; F Porrot; F Tanneau-Salvadori; P Sansonetti; O Lopez; G Pialoux; V Feuillie; M Mollereau; S Chamaret Journal: AIDS Res Hum Retroviruses Date: 1995-08 Impact factor: 2.205
Authors: M R Klein; C A van Baalen; A M Holwerda; S R Kerkhof Garde; R J Bende; I P Keet; J K Eeftinck-Schattenkerk; A D Osterhaus; H Schuitemaker; F Miedema Journal: J Exp Med Date: 1995-04-01 Impact factor: 14.307
Authors: Jaclyn K Wright; Vladimir Novitsky; Mark A Brockman; Zabrina L Brumme; Chanson J Brumme; Jonathan M Carlson; David Heckerman; Bingxia Wang; Elena Losina; Mopo Leshwedi; Mary van der Stok; Lungile Maphumulo; Nompumelelo Mkhwanazi; Fundisiwe Chonco; Philip J R Goulder; Max Essex; Bruce D Walker; Thumbi Ndung'u Journal: J Virol Date: 2011-02-02 Impact factor: 5.103
Authors: Amy W Chung; Jenniffer M Mabuka; Bongiwe Ndlovu; Anna Licht; Hannah Robinson; Yathisha Ramlakhan; Musie Ghebremichael; Tarylee Reddy; Philip J R Goulder; Bruce D Walker; Thumbi Ndung'u; Galit Alter Journal: AIDS Date: 2018-06-19 Impact factor: 4.177
Authors: Jaclyn K Wright; Zabrina L Brumme; Jonathan M Carlson; David Heckerman; Carl M Kadie; Chanson J Brumme; Bingxia Wang; Elena Losina; Toshiyuki Miura; Fundisiwe Chonco; Mary van der Stok; Zenele Mncube; Karen Bishop; Philip J R Goulder; Bruce D Walker; Mark A Brockman; Thumbi Ndung'u Journal: J Virol Date: 2010-08-11 Impact factor: 5.103
Authors: Jianming Tang; Rakhi Malhotra; Wei Song; Ilene Brill; Liangyuan Hu; Paul K Farmer; Joseph Mulenga; Susan Allen; Eric Hunter; Richard A Kaslow Journal: PLoS One Date: 2010-03-10 Impact factor: 3.240
Authors: Heather A Prentice; Travis R Porter; Matthew A Price; Emmanuel Cormier; Dongning He; Paul K Farmer; Anatoli Kamali; Etienne Karita; Shabir Lakhi; Eduard J Sanders; Omu Anzala; Pauli N Amornkul; Susan Allen; Eric Hunter; Richard A Kaslow; Jill Gilmour; Jianming Tang Journal: J Virol Date: 2013-01-30 Impact factor: 5.103