BACKGROUND: Although antiretroviral therapy has the ability to fully restore a normal CD4(+) cell count (>500 cells/mm(3)) in most patients, it is not yet clear whether all patients can achieve normalization of their CD4(+) cell count, in part because no study has followed up patients for >7 years. METHODS: Three hundred sixty-six patients from 5 clinical cohorts who maintained a plasma human immunodeficiency virus (HIV) RNA level 1000 copies/mL for at least 4 years after initiation of antiretroviral therapy were included. Changes in CD4(+) cell count were evaluated using mixed-effects modeling, spline-smoothing regression, and Kaplan-Meier techniques. RESULTS: The majority (83%) of the patients were men. The median CD4(+) cell count at the time of therapy initiation was 201 cells/mm(3) (interquartile range, 72-344 cells/mm(3)), and the median age was 47 years. The median follow-up period was 7.5 years (interquartile range, 5.5-9.7 years). CD4(+) cell counts continued to increase throughout the follow-up period, albeit slowly after year 4. Although almost all patients (95%) who started therapy with a CD4(+) cell count 300 cells/mm(3) were able to attain a CD4(+) cell count 500 cells/mm(3), 44% of patients who started therapy with a CD4(+) cell count <100 cells/mm(3) and 25% of patients who started therapy with a CD4(+) cell count of 100-200 cells/mm(3) were unable to achieve a CD4(+) cell count >500 cells/mm(3) over a mean duration of follow-up of 7.5 years; many did not reach this threshold by year 10. Twenty-four percent of individuals with a CD4(+) cell count <500 cells/mm(3) at year 4 had evidence of a CD4(+) cell count plateau after year 4. The frequency of detectable viremia ("blips") after year 4 was not associated with the magnitude of the CD4(+) cell count change. CONCLUSIONS: A substantial proportion of patients who delay therapy until their CD4(+) cell count decreases to <200 cells/mm(3) do not achieve a normal CD4(+) cell count, even after a decade of otherwise effective antiretroviral therapy. Although the majority of patients have evidence of slow increases in their CD4(+) cell count over time, many do not. These individuals may have an elevated risk of non-AIDS-related morbidity and mortality.
BACKGROUND: Although antiretroviral therapy has the ability to fully restore a normal CD4(+) cell count (>500 cells/mm(3)) in most patients, it is not yet clear whether all patients can achieve normalization of their CD4(+) cell count, in part because no study has followed up patients for >7 years. METHODS: Three hundred sixty-six patients from 5 clinical cohorts who maintained a plasma human immunodeficiency virus (HIV) RNA level 1000 copies/mL for at least 4 years after initiation of antiretroviral therapy were included. Changes in CD4(+) cell count were evaluated using mixed-effects modeling, spline-smoothing regression, and Kaplan-Meier techniques. RESULTS: The majority (83%) of the patients were men. The median CD4(+) cell count at the time of therapy initiation was 201 cells/mm(3) (interquartile range, 72-344 cells/mm(3)), and the median age was 47 years. The median follow-up period was 7.5 years (interquartile range, 5.5-9.7 years). CD4(+) cell counts continued to increase throughout the follow-up period, albeit slowly after year 4. Although almost all patients (95%) who started therapy with a CD4(+) cell count 300 cells/mm(3) were able to attain a CD4(+) cell count 500 cells/mm(3), 44% of patients who started therapy with a CD4(+) cell count <100 cells/mm(3) and 25% of patients who started therapy with a CD4(+) cell count of 100-200 cells/mm(3) were unable to achieve a CD4(+) cell count >500 cells/mm(3) over a mean duration of follow-up of 7.5 years; many did not reach this threshold by year 10. Twenty-four percent of individuals with a CD4(+) cell count <500 cells/mm(3) at year 4 had evidence of a CD4(+) cell count plateau after year 4. The frequency of detectable viremia ("blips") after year 4 was not associated with the magnitude of the CD4(+) cell count change. CONCLUSIONS: A substantial proportion of patients who delay therapy until their CD4(+) cell count decreases to <200 cells/mm(3) do not achieve a normal CD4(+) cell count, even after a decade of otherwise effective antiretroviral therapy. Although the majority of patients have evidence of slow increases in their CD4(+) cell count over time, many do not. These individuals may have an elevated risk of non-AIDS-related morbidity and mortality.
Authors: L Teixeira; H Valdez; J M McCune; R A Koup; A D Badley; M K Hellerstein; L A Napolitano; D C Douek; G Mbisa; S Deeks; J M Harris; J D Barbour; B H Gross; I R Francis; R Halvorsen; R Asaad; M M Lederman Journal: AIDS Date: 2001-09-28 Impact factor: 4.177
Authors: P M Tarwater; J B Margolick; J Jin; J P Phair; R Detels; C Rinaldo; J Giorgi; A Muñoz Journal: J Acquir Immune Defic Syndr Date: 2001-06-01 Impact factor: 3.731
Authors: Timothy W Schacker; Phuong L Nguyen; Esteban Martinez; Cavan Reilly; Jose M Gatell; Andrzej Horban; Elzbieta Bakowska; Baiba Berzins; Remko van Leeuwen; Steven Wolinsky; Ashley T Haase; Robert L Murphy Journal: J Infect Dis Date: 2002-09-20 Impact factor: 5.226
Authors: Diane V Havlir; Matthew C Strain; Mario Clerici; Caroline Ignacio; Daria Trabattoni; Pasquale Ferrante; Joseph K Wong Journal: J Virol Date: 2003-10 Impact factor: 5.103
Authors: Gilbert R Kaufmann; Luc Perrin; Guiseppe Pantaleo; Milos Opravil; Hansjakob Furrer; Amalio Telenti; Bernard Hirschel; Bruno Ledergerber; Pietro Vernazza; Enos Bernasconi; Martin Rickenbach; Matthias Egger; Manuel Battegay Journal: Arch Intern Med Date: 2003-10-13
Authors: Peter W Hunt; Jeffrey N Martin; Elizabeth Sinclair; Barry Bredt; Elilta Hagos; Harry Lampiris; Steven G Deeks Journal: J Infect Dis Date: 2003-04-23 Impact factor: 5.226
Authors: Peter W Hunt; Steven G Deeks; Benigno Rodriguez; Hernan Valdez; Starley B Shade; Donald I Abrams; Mari M Kitahata; Melissa Krone; Torsten B Neilands; Richard J Brand; Michael M Lederman; Jeffrey N Martin Journal: AIDS Date: 2003-09-05 Impact factor: 4.177
Authors: Hernan Valdez; Elizabeth Connick; Kimberly Y Smith; Michael M Lederman; Ronald J Bosch; Ryung S Kim; Marty St Clair; Daniel R Kuritzkes; Harold Kessler; Lawrence Fox; Michelle Blanchard-Vargas; Alan Landay Journal: AIDS Date: 2002-09-27 Impact factor: 4.177
Authors: Felipe García; Elisa de Lazzari; Montserrat Plana; Pedro Castro; Gabriel Mestre; Meritxell Nomdedeu; Emilio Fumero; Esteban Martínez; Josep Mallolas; José L Blanco; José M Miró; Tomás Pumarola; Teresa Gallart; José M Gatell Journal: J Acquir Immune Defic Syndr Date: 2004-06-01 Impact factor: 3.731
Authors: Amina A Chaudhry; Gail Berkenblit; Allen L Gifford; Joseph Cofrancesco; James Sosman; Lynn E Sullivan Journal: J Gen Intern Med Date: 2010-12-08 Impact factor: 5.128
Authors: L Lourenço; H Samji; A Nohpal; W Chau; G Colley; K Lepik; R Barrios; V Lima; R S Hogg; Jsg Montaner; S Kesselring; D M Moore Journal: HIV Med Date: 2015-02-27 Impact factor: 3.180
Authors: Lillian Seu; Steffanie Sabbaj; Alexandra Duverger; Frederic Wagner; Joshua C Anderson; Elizabeth Davies; Frank Wolschendorf; Christopher D Willey; Michael S Saag; Paul Goepfert; Olaf Kutsch Journal: J Virol Date: 2015-04-15 Impact factor: 5.103
Authors: Jessie K Edwards; Stephen R Cole; Jeffrey N Martin; Richard Moore; W Christopher Mathews; Mari Kitahata; Joseph J Eron; Michael Saag; Michael J Mugavero Journal: Clin Infect Dis Date: 2015-04-01 Impact factor: 9.079
Authors: Caroline O Tabler; Mark B Lucera; Aiman A Haqqani; David J McDonald; Stephen A Migueles; Mark Connors; John C Tilton Journal: J Virol Date: 2014-02-19 Impact factor: 5.103
Authors: Douglas S Bell; Laral Cima; Danielle S Seiden; Terry T Nakazono; Marcia S Alcouloumre; William E Cunningham Journal: Int J Med Inform Date: 2012-08-17 Impact factor: 4.046
Authors: Xinyan Zhang; Peter W Hunt; Scott M Hammer; Michelle S Cespedes; Kristine B Patterson; Ronald J Bosch Journal: HIV Clin Trials Date: 2013 Mar-Apr