Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery

AIDS

Volumn 29, Issue 16, 2015, Pages 2121-2129

  Cillo, Anthony R ^a   Hilldorfer, Benedict B ^a   Lalama, Christina M ^b   McKinnon, John E ^a,c   Coombs, Robert W ^d   Tenorio, Allan R ^e   Fox, Lawrence ^f   Gandhi, Rajesh T ^g   Ribaudo, Heather ^b   Currier, Judith S ^h   Gulick, Roy M ⁱ   Wilkin, Timothy J ⁱ   Mellors, John W ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b CENTER FOR BIOSTATISTICS IN AIDS RESEARCH   (United States)

^c HENRY FORD HOSPITAL   (United States)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^e RUSH UNIVERSITY MEDICAL CENTER   (United States)

^f NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^g MASSACHUSETTS GENERAL HOSPITAL   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

antiretroviral therapy intensification; HIV 1 immunotherapeutics; HIV 1 persistence; maraviroc; suboptimal T cell recovery

Indexed keywords

CASPASE 3; HLA DR ANTIGEN; MARAVIROC; PROTEIN BCL 2; VIRUS DNA; ANTIRETROVIRUS AGENT; CYCLOHEXANE DERIVATIVE; TRIAZOLE DERIVATIVE;

ANTIVIRAL THERAPY; APOPTOSIS; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CLINICAL ARTICLE; DISEASE ASSOCIATION; DRUG BLOOD LEVEL; DRUG EFFECT; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOLOGICAL PARAMETERS; IMMUNOSUPPRESSIVE TREATMENT; LONG TERMINAL REPEAT; MULTICENTER STUDY; NONHUMAN; OPEN STUDY; PERIPHERAL BLOOD MONONUCLEAR CELL; PILOT STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; TREATMENT DURATION; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; FEMALE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HIV INFECTIONS; IMMUNOLOGY; ISOLATION AND PURIFICATION; MALE; MIDDLE AGED; PATHOLOGY; PROCEDURES; TREATMENT OUTCOME; VIROLOGY; VIRUS LOAD;

ANTI-RETROVIRAL AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CYCLOHEXANES; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; TREATMENT OUTCOME; TRIAZOLES; VIRAL LOAD;

EID: 84964832117     PISSN: 02699370     EISSN: 14735571     Source Type: Journal    
DOI: 10.1097/QAD.0000000000000810     Document Type: Article

References (40)

1. Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 1997; 387:188-191.
2. Andrade A, Rosenkranz SL, Cillo AR, Lu D, Daar ES, Jacobson JM, et al. Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248. J Infect Dis 2013; 208:884-891.
3. Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med 1997; 337:725-733.
4. Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, et al. Positive effects of combined antiretroviral therapy on CD4R T cell homeostasis and function in advanced HIV disease. Science 1997; 277:112-116.
5. Bartlett JA, Fath MJ, Demasi R, Hermes A, Quinn J, Mondou E, et al. An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults. AIDS 2006; 20:2051-2064.
6. Li TS, Tubiana R, Katlama C, Calvez V, Ait Mohand H, Autran B. Long-lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease. Lancet 1998; 351:1682-1686.
7. Piketty C, Castiel P, Belec L, Batisse D, Si Mohamed A, Gilquin J, et al. Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease. AIDS 1998; 12:745-750.
8. Grabar S. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 2000; 133:401-410.
9. Piketty C, Weiss L, Thomas F, Mohamed AS, Belec L, Kazatchkine MD. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. J Infect Dis 2001; 183:1328-1335.
10. Moore DM, Hogg RS, Yip B, Wood E, Tyndall M, Braitstein P, et al. Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr 2005; 40:288-293.
11. Önen NF, Overton ET, Presti R, Blair C, Powderly WG, Mondy K. Sub-optimal CD4 recovery on long-term suppressive highly active antiretroviral therapy is associated with favourable outcome. HIV Med 2009; 10:439-446.
12. Wilkin TJ, Ribaudo HR, Tenorio AR, Gulick RM. The Relationship of CCR5 antagonists to CD4R T-cell gain: a meta-regression of recent clinical trials in treatment-experienced HIVinfected patients. HIV Clin Trials 2010; 11:351-358.
13. Wilkin TJ, Lalama CM, McKinnon J, Gandhi RT, Lin N, Landay A, et al. A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4R T-cell recovery despite sustained virologic suppression: ACTG A5256. J Infect Dis 2012; 206:534-542.
14. Rusconi S, Vitiello P, Adorni F, Colella E, Focà E, Capetti A, et al. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PLoS One 2013; 8:e80157.
15. Lafeuillade A, Assi A, Poggi C, Bresson-Cuquemelle C, Jullian E, Tamalet C. Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial. AIDS Res Ther 2014; 11:33.
16. Gutiérrez C, Díaz L, Vallejo A, Hernández-Novoa B, Abad M, Madrid N, et al. Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection: effect on T cells latently infected. PLoS One 2011; 6:e27864.
17. Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, et al. Blockade of lymphocyte chemotaxis in visceral graftversus- host disease. N Engl J Med 2012; 367:135-145.
18. Hunt PW, Shulman NS, Hayes TL, Dahl V, Somsouk M, Funderburg NT, et al. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4R T-cell recovery: a randomized trial. Blood 2013; 121:4635-4646.
19. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, et al. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Micro 2003; 41:4531-4536.
20. Gandhi RT. No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy. J Acquir Immune Decif Snydr 2012; 59:229-235.
21. Sharkey M, Stevenson M. Persistence of episomal HIV-1 infection intermediates in patients on highly active antiretroviral therapy. Nat Med 2000; 6:76-81.
22. Brussel A, Mathez D, Broche-Pierre S, Lancar R, Calvez T, Sonigo P, et al. Longitudinalmonitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection. AIDS 2003; 17:645-652.
23. Zuckerman RA, Lucchetti A, Whittington WLH, Sánchez J, Coombs RW, Zuñiga R, et al. Herpes Simplex Virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis 2007; 196:1500-1508.
24. Yukl SA, Gianella S, Sinclair E, Epling L, Li Q, Duan L, et al. Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis 2010; 202:1553-1561.
25. Dinoso JB, Maldarelli F. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A 2009; 106:9403-9408.
26. McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, et al. Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis 2010; 50:912-919.
27. Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, Read S, et al. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med 2010; 7:e1000321.
28. Hatano H, Hayes TL, Dahl V, Sinclair E, Lee T-H, Hoh R, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4R T cell response. J Infect Dis 2011; 203:960-968.
29. Madrid-Elena N, Hernandez-Novoa B, Garcia-Bermejo L, Moreno S. Maraviroc (MVC) intensification can activate NFkB through CCR5 and the expression of its target genes in resting CD4R T cells in suppressed HIV-1-infected patients [Abstract no. MOLBPE02]. 7th IAS Conference on HIV Pathogenesis and Treatment, 3-6 December 2013, Miami, FL.
30. Dorr P, Westby M, Dobbs S, Griffin P, Irvine B, Macartney M, et al. Maraviroc (UK-427 857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum antihuman immunodeficiency virus type 1 activity. Antimicrobial Agents Chemo 2005; 49:4721-4732.
31. Beliakova-Bethell N, Jain S, Woelk CH, Witt MD, Sun X, Lada SM, et al. Maraviroc intensification in patients with suppressed HIV viremia has limited effects on CD4R T cell recovery and gene expression. Antiviral Res 2014; 107:42-49.
32. Besson GJ, Lalama CM, Bosch RJ, Gandhi RT, Bedison MA, Aga E, et al. HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy. Clin Infect Dis 2014; 59:1312-1321.
33. Hatano H, Jain V, Hunt PW, Lee T-H, Sinclair E, Do TD, et al. Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD- 1)-expressing CD4R T cells. J Infect Dis 2013; 208:50-56.
34. Piconi S, Trabattoni D, Gori A, Parisotto S, Magni C, Meraviglia P, et al. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4R T-cell counts during antiretroviral therapy. AIDS 2010; 24:1991-2000.
35. Nakanjako D, Ssewanyana I, Mayanja-Kizza H, Kiragga A, Colebunders R, Manabe YC, et al. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infect Dis 2011; 11:43.
36. Gougeon ML, Lecoeur H, Dulioust A, Enouf MG, Crouvosier M, Goujard C, et al. Programmed cell death in peripheral lymphocytes from HIV-infected persons. J Immunol 1996; 156:3509-3520.
37. Badley AD, Parato K, Cameron DW, Kravcik S, Phenix BN, Ashby D, et al. Dynamic correlation of apoptosis and immune activation during treatment of HIV infection. Cell Death Differ 1999; 6:420-432.
38. Marziali M, De Santis W, Carello R, Leti W, Esposito A, Isgrò A, et al. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS 2006; 20:2033-2041.
39. Areras H, Guardo AC, Bargallo ME, Maleno MJ, Calvo M, Blanco JL, et al. In vitro effects of the CCR5 inhibitor maraviroc on human T cell function. J Antimicrob Chemother 2013; 68:577-586.
40. Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H, et al. Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4R T cells rises in HIV-infected patients. PLoS One 2010; 5:e13188.