Literature DB >> 22740718

A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256.

Timothy J Wilkin1, 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.   

Abstract

BACKGROUND: Despite viral suppression, antiretroviral therapy (ART) does not restore CD4(+) T-cell counts in many patients infected with human immunodeficiency virus type 1 (HIV-1).
METHODS: In a single-arm pilot trial involving ART recipients with suppressed plasma levels of HIV-1 RNA for at least 48 weeks and stable suboptimal CD4(+) T-cell recovery, subjects added maraviroc, a CCR5 antagonist, to their existing ART for 24 weeks. After stopping maraviroc, they were followed for an additional 24 weeks. A Wilcoxon signed-rank test was used to evaluate whether maraviroc was associated with an increase of at least 20 cells/µL in the CD4(+) T-cell count.
RESULTS: A total of 34 subjects were enrolled. The median age was 50 years, and the median baseline CD4(+) T-cell count was 153 cells/µL. The median increase in CD4(+) T-cell count from baseline to week 22/24 was 12 cells/µL (90% confidence interval, 1-22). A CD4(+) T-cell count increase of at least 20 cells/µL was not detected (P = .97). Markers of immune activation and apoptosis decreased during maraviroc intensification; this decline partially reversed after discontinuing maraviroc.
CONCLUSIONS: Adding maraviroc to suppressive ART for 24 weeks was not associated with an increase in CD4(+) T-cell counts of at least 20 cells/µL. Further studies of CCR5 antagonists in the dampening of immune activation associated with HIV infection are warranted. Clinical Trials Registration. NCT 00709111.

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Year:  2012        PMID: 22740718      PMCID: PMC3491731          DOI: 10.1093/infdis/jis376

Source DB:  PubMed          Journal:  J Infect Dis        ISSN: 0022-1899            Impact factor:   5.226


  30 in total

1.  Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384.

Authors:  Rajesh T Gandhi; John Spritzler; Ellen Chan; David M Asmuth; Benigno Rodriguez; Thomas C Merigan; Martin S Hirsch; Robert W Shafer; Gregory K Robbins; Richard B Pollard
Journal:  J Acquir Immune Defic Syndr       Date:  2006-08-01       Impact factor: 3.731

2.  Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City.

Authors:  Judith E Sackoff; David B Hanna; Melissa R Pfeiffer; Lucia V Torian
Journal:  Ann Intern Med       Date:  2006-09-19       Impact factor: 25.391

3.  Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.

Authors:  Rainer Weber; Caroline A Sabin; Nina Friis-Møller; Peter Reiss; Wafaa M El-Sadr; Ole Kirk; Francois Dabis; Matthew G Law; Christian Pradier; Stephane De Wit; Börje Akerlund; Gonzalo Calvo; Antonella d'Arminio Monforte; Martin Rickenbach; Bruno Ledergerber; Andrew N Phillips; Jens D Lundgren
Journal:  Arch Intern Med       Date:  2006 Aug 14-28

4.  Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.

Authors:  David A Cooper; Jayvant Heera; James Goodrich; Margaret Tawadrous; Michael Saag; Edwin Dejesus; Nathan Clumeck; Sharon Walmsley; Naitee Ting; Eoin Coakley; Jacqueline D Reeves; Gustavo Reyes-Teran; Mike Westby; Elna Van Der Ryst; Prudence Ive; Lerato Mohapi; Horacio Mingrone; Andrzej Horban; Frances Hackman; John Sullivan; Howard Mayer
Journal:  J Infect Dis       Date:  2010-03-15       Impact factor: 5.226

5.  Treatment initiation with zidovudine-containing potent antiretroviral therapy impairs CD4 cell count recovery but not clinical efficacy.

Authors:  Angela C Huttner; Gilbert R Kaufmann; Manuel Battegay; Rainer Weber; Milos Opravil
Journal:  AIDS       Date:  2007-05-11       Impact factor: 4.177

6.  Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression.

Authors:  Roger J Bedimo; Kathleen A McGinnis; Melinda Dunlap; Maria C Rodriguez-Barradas; Amy C Justice
Journal:  J Acquir Immune Defic Syndr       Date:  2009-10-01       Impact factor: 3.731

7.  Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy.

Authors:  Benoît Marin; Rodolphe Thiébaut; Heiner C Bucher; Virginie Rondeau; Dominique Costagliola; Maria Dorrucci; Osamah Hamouda; Maria Prins; Sarah Walker; Kholoud Porter; Caroline Sabin; Geneviève Chêne
Journal:  AIDS       Date:  2009-08-24       Impact factor: 4.177

8.  CCR5 expression levels influence NFAT translocation, IL-2 production, and subsequent signaling events during T lymphocyte activation.

Authors:  Jose F Camargo; Marlon P Quinones; Srinivas Mummidi; Sowmya Srinivas; Alvaro A Gaitan; Kazi Begum; Fabio Jimenez; Scott VanCompernolle; Derya Unutmaz; Seema S Ahuja; Sunil K Ahuja
Journal:  J Immunol       Date:  2009-01-01       Impact factor: 5.422

9.  Interleukin-2 therapy in patients with HIV infection.

Authors:  D Abrams; Y Lévy; M H Losso; A Babiker; G Collins; D A Cooper; J Darbyshire; S Emery; L Fox; F Gordin; H C Lane; J D Lundgren; R Mitsuyasu; J D Neaton; A Phillips; J P Routy; G Tambussi; D Wentworth
Journal:  N Engl J Med       Date:  2009-10-15       Impact factor: 91.245

10.  Incidence and outcomes of malignancy in the HAART era in an urban cohort of HIV-infected individuals.

Authors:  Jessica L Long; Eric A Engels; Richard D Moore; Kelly A Gebo
Journal:  AIDS       Date:  2008-02-19       Impact factor: 4.177

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  36 in total

Review 1.  Serious Non-AIDS Events: Therapeutic Targets of Immune Activation and Chronic Inflammation in HIV Infection.

Authors:  Denise C Hsu; Irini Sereti
Journal:  Drugs       Date:  2016-04       Impact factor: 9.546

2.  Maraviroc intensification in patients with suppressed HIV viremia has limited effects on CD4+ T cell recovery and gene expression.

Authors:  Nadejda Beliakova-Bethell; Sonia Jain; Christopher H Woelk; Mallory D Witt; Xiaoying Sun; Steven M Lada; Celsa A Spina; Miguel Goicoechea; Steffney E Rought; Richard Haubrich; Michael P Dubé
Journal:  Antiviral Res       Date:  2014-04-24       Impact factor: 5.970

Review 3.  Inflammatory co-morbidities in HIV+ individuals: learning lessons from healthy ageing.

Authors:  Anna C Hearps; Genevieve E Martin; Reena Rajasuriar; Suzanne M Crowe
Journal:  Curr HIV/AIDS Rep       Date:  2014-03       Impact factor: 5.071

4.  The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM.

Authors:  Ian McGowan; Timothy Wilkin; Raphael J Landovitz; Chunyuan Wu; Ying Chen; Mark A Marzinke; Craig W Hendrix; Paul Richardson; Susan H Eshleman; Adriana Andrade; Wairimu Chege; Peter L Anderson; Marybeth McCauley; Jason Farley; Kenneth H Mayer; Peter Anton; Rhonda M Brand; Ross D Cranston; Roy Gulick
Journal:  AIDS       Date:  2019-02-01       Impact factor: 4.177

5.  Marginal Effects of Systemic CCR5 Blockade with Maraviroc on Oral Simian Immunodeficiency Virus Transmission to Infant Macaques.

Authors:  Egidio Brocca-Cofano; Cuiling Xu; Katherine S Wetzel; Mackenzie L Cottrell; Benjamin B Policicchio; Kevin D Raehtz; Dongzhu Ma; Tammy Dunsmore; George S Haret-Richter; Karam Musaitif; Brandon F Keele; Angela D Kashuba; Ronald G Collman; Ivona Pandrea; Cristian Apetrei
Journal:  J Virol       Date:  2018-08-16       Impact factor: 5.103

6.  Persistent immune activation in chronic HIV infection: do any interventions work?

Authors:  Reena Rajasuriar; Gabriela Khoury; Adeeba Kamarulzaman; Martyn A French; Paul U Cameron; Sharon R Lewin
Journal:  AIDS       Date:  2013-05-15       Impact factor: 4.177

Review 7.  Understanding and controlling chronic immune activation in the HIV-infected patients suppressed on combination antiretroviral therapy.

Authors:  Babafemi Taiwo; Luis Barcena; Randall Tressler
Journal:  Curr HIV/AIDS Rep       Date:  2013-03       Impact factor: 5.071

8.  The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial.

Authors:  Peter W Hunt; Nancy S Shulman; Timothy L Hayes; Viktor Dahl; Ma Somsouk; Nicholas T Funderburg; Bridget McLaughlin; Alan L Landay; Oluwatoyin Adeyemi; Lee E Gilman; Brian Clagett; Benigno Rodriguez; Jeffrey N Martin; Timothy W Schacker; Barbara L Shacklett; Sarah Palmer; Michael M Lederman; Steven G Deeks
Journal:  Blood       Date:  2013-04-15       Impact factor: 22.113

Review 9.  Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs.

Authors:  Eleanor M P Wilson; Irini Sereti
Journal:  Immunol Rev       Date:  2013-07       Impact factor: 12.988

Review 10.  CROI 2013: Advances in antiretroviral therapy.

Authors:  Barbara S Taylor; Timothy J Wilkin; Noga Shalev; Scott M Hammer
Journal:  Top Antivir Med       Date:  2013 Apr-May
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