Bret J Rudy1, Bill G Kapogiannis, Carol Worrell, Kathleen Squires, James Bethel, Su Li, Craig M Wilson, Allison Agwu, Patricia Emmanuel, Georgine Price, Stephanie Hudey, Maureen M Goodenow, John W Sleasman. 1. *New York University School of Medicine, New York, NY; †The Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, Bethesda, MD; ‡Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA; §Westat, Rockville, MD; ‖University of Alabama at Birmingham; ¶Johns Hopkins School of Medicine; #University of South Florida School of Medicine, Tampa, FL; **University of Florida Health Science Center, Gainsville, FL; and ††Duke University School of Medicine, Durham, NC.
Abstract
BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48. METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls. RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CM CD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls. CONCLUSIONS: In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls.
BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48. METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls. RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CMCD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls. CONCLUSIONS: In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls.
Authors: Mark A Wallet; Carina A Rodriguez; Li Yin; Sara Saporta; Sasawan Chinratanapisit; Wei Hou; John W Sleasman; Maureen M Goodenow Journal: AIDS Date: 2010-06-01 Impact factor: 4.177
Authors: Christine Katlama; Marc A Valantin; Michele Algarte-Genin; Claudine Duvivier; Sidonie Lambert-Niclot; Pierre M Girard; Jean M Molina; Bruno Hoen; Sophie Pakianather; Gilles Peytavin; Anne G Marcelin; Philippe Flandre Journal: AIDS Date: 2010-09-24 Impact factor: 4.177
Authors: Jose R Arribas; Andrzej Horban; Jan Gerstoft; Gerdt Fätkenheuer; Mark Nelson; Nathan Clumeck; Federico Pulido; Andrew Hill; Yvon van Delft; Thomas Stark; Christiane Moecklinghoff Journal: AIDS Date: 2010-01-16 Impact factor: 4.177
Authors: Frederik N Engsig; Jan Gerstoft; Gitte Kronborg; Carsten S Larsen; Gitte Pedersen; Birgit Røge; Janne Jensen; Lars N Nielsen; Niels Obel Journal: BMC Infect Dis Date: 2010-11-02 Impact factor: 3.090
Authors: Joseph N Brown; James J Kohler; Carter R Coberley; John W Sleasman; Maureen M Goodenow Journal: PLoS One Date: 2008-12-02 Impact factor: 3.240
Authors: Julie J Kim-Chang; Lorena Wilson; Cliburn Chan; Bernard Fischer; Guglielmo Venturi; Maureen M Goodenow; Grace Aldrovandi; Thomas J Weber; John W Sleasman Journal: AIDS Res Hum Retroviruses Date: 2019-06-27 Impact factor: 2.205
Authors: Matteo Vassallo; R Fabre; J Durant; C Lebrun-Frenay; H Joly; M Ticchioni; F DeSalvador; A Harvey-Langton; B Dunais; M Laffon; J Cottalorda; P Dellamonica; C Pradier Journal: J Neurovirol Date: 2016-11-04 Impact factor: 2.643
Authors: Florin Tuluc; Sergei Spitsin; Nancy B Tustin; Jennifer B Murray; Richard Tustin; Laura A Schankel; Andrew Wiznia; Sharon Nachman; Steven D Douglas Journal: AIDS Res Hum Retroviruses Date: 2016-10-18 Impact factor: 2.205
Authors: Tanya L Kowalczyk Mullins; Su X Li; James Bethel; Maureen M Goodenow; Stephanie Hudey; John W Sleasman Journal: J Clin Virol Date: 2018-02-07 Impact factor: 3.168