Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: A randomized 48-week study

Antiviral Therapy

Volumn 17, Issue 2, 2012, Pages 355-364

  Llibre, Josep M ^a   Buzón, Maria J ^b   Massanella, Marta ^b   Esteve, Anna ^c   Dahl, Viktor ^d   Puertas, Maria C ^b   Domingo, Pere ^e   Gatell, Josep M ^f   Larrouse, Maria ^f   Mar, Gutierrez ^e   Palmer, Sarah ^d   Stevenson, Mario ^g   Blanco, Julià ^b   Martinez Picado, Javier ^b,h   Clotet, Bonaventura ^a,b  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b IrsiCaixa Foundation   (Spain)

^c Center for Epidemiological Studies on STI and HIV/AIDS of Catalonia   (Spain)

^d SWEDISH INSTITUTE FOR INFECTIOUS DISEASE CONTROL   (Sweden)

^e Hospital Sant Pau   (Spain)

^f INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^g UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^h INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CD38 ANTIGEN; CD45RO ANTIGEN; CD8 ANTIGEN; HLA DR ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RALTEGRAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS DNA;

ARTICLE; CD4 LYMPHOCYTE COUNT; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG SAFETY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LONG TERMINAL REPEAT; MAJOR CLINICAL STUDY; MULTICENTER STUDY; OPEN STUDY; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; SPAIN; T LYMPHOCYTE ACTIVATION; UNIVERSITY HOSPITAL; VIREMIA; VIRUS LOAD;

ADULT; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; DNA, VIRAL; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; PYRROLIDINONES; RNA, VIRAL; VIRAL LOAD; VIREMIA;

EID: 84860345691     PISSN: 13596535     EISSN: None     Source Type: Journal    
DOI: 10.3851/IMP1917     Document Type: Article

References (42)

1. Jiang W, Lederman MM, Hunt P, et al. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis 2009; 199:1177-1185.
2. Louie M, Hogan C, Di Mascio M, et al. Determining the relative effcacy of highly active antiretroviral therapy. J Infect Dis 2003; 187:896-900. (Pubitemid 36337901)
3. Perelson AS, Essunger P, Ho DD. Dynamics of HIV-1 and CD4+ lymphocytes in vivo. AIDS 1997; 11 Suppl A:S17-S24.
4. Perelson AS, Essunger P, Cao Y, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 1997; 387:188-191. (Pubitemid 27209434)
5. Rong L, Perelson AS. Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. PLOS Comput Biol 2009; 5:e1000533.
6. Brennan TP, Woods JO, Sedaghat AR, Siliciano JD, Siliciano RF, Wilke CO. Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy. J Virol 2009; 83:8470-8481.
7. Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS. Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A 1998; 95:8869-8873. (Pubitemid 28350581)
8. Zhang L, Ramratnam B, Tenner-Racz K, et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 1999; 340:1605-1613. (Pubitemid 29249429)
9. Dornadula G, Zhang H, VanUitert B, et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA 1999; 282:1627-1632. (Pubitemid 29513968)
10. Trono D, Van Lint C, Rouzioux C, et al. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 2010; 329:174-180.
11. Yukl SA, Shergill AK, McQuaid K, et al. Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy. AIDS 2010; 24:2451-2460.
12. Dinoso JB, Kim SY, Wiegand AM, et al. 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.
13. Gandhi RT, Bosch RJ, Aga E, et al. No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy. J Infect Dis 2010; 201:293-296.
14. Gandhi RT, Zheng L, Bosch RJ, 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.
15. McMahon D, Jones J, Wiegand A, 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.
16. Sedaghat AR, Siliciano JD, Brennan TP, Wilke CO, Siliciano RF. Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART. PLoS Pathog 2007; 3:e122.
17. Stepanyuk O, Chiang TS, Dever LL, et al. Impact of adding maraviroc to antiretroviral regimens in patients with full viral suppression but impaired CD4 recovery. AIDS 2009; 23:1911-1913.
18. Ramratnam B, Ribeiro R, He T, et al. Intensification of antiretroviral therapy accelerates the decay of the HIV-1 latent reservoir and decreases, but does not eliminate, ongoing virus replication. J Acquir Immune Defic Syndr 2004; 35:33-37. (Pubitemid 38044779)
19. van Praag RM, Wit FW, Jurriaans S, de Wolf F, Prins JM, Lange JM. Improved long-term suppression of HIV-1 replication with a triple-class multidrug regimen compared with standard of care antiretroviral therapy. AIDS 2002; 16:719-725. (Pubitemid 34274462)
20. Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis 2003; 187:1534-1543. (Pubitemid 36578959)
21. Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999; 179:859-870. (Pubitemid 29159331)
22. Hazuda DJ, Felock P, Witmer M, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000; 287:646-650. (Pubitemid 30070911)
23. Petitjean G, Al Tabaa Y, Tuaillon E, et al. Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients. Retrovirology 2007; 4:60.
24. Sharkey M, Triques K, Kuritzkes DR, Stevenson M. In vivo evidence for instability of episomal human immunodeficiency virus type 1 cDNA. J Virol 2005; 79:5203-5210. (Pubitemid 40464268)
25. Buzón MJ, Massanella M, Llibre JM, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 2010; 16:460-465.
26. Landay A, da Silva BA, King MS, et al. Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment. Clin Infect Dis 2007; 44:749-754.
27. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 2007; 44:441-446. (Pubitemid 46147630)
28. Deeks SG. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med 2009; 17:118-123.
29. Dubé M P, Sattler FR. Inflammation and complications of HIV disease. J Infect Dis 2010; 201:1783-1785.
30. Bourgeois C, Hao Z, Rajewsky K, Potocnik AJ, Stockinger B. Ablation of thymic export causes accelerated decay of naive CD4 T cells in the periphery because of activation by environmental antigen. Proc Natl Acad Sci U S A 2008; 105:8691-8696. (Pubitemid 351987742)
31. Brenchley JM, Price DA, Schacker T W, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12:1365-1371. (Pubitemid 44924494)
32. Catalfamo M, Di Mascio M, Hu Z, et al. HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells. Proc Natl Acad Sci U S A 2008; 105:19851-19856.
33. Hatano H, Hayes TL, Dahl V, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis 2011; 203:960-968.
34. Hunt PW, Martin JN, Sinclair E, et al. Valganciclovir Reduces T Cell Activation in HIV-infected Individuals With Incomplete CD4+ T Cell Recovery on Antiretroviral Therapy. J Infect Dis 2011; 203:1474-1483.
35. Yukl SA, Gianella S, Sinclair E, et al. Differences in HIV burden and immune activation within the gut of HIVpositive patients receiving suppressive antiretroviral therapy. J Infect Dis 2010; 202:1553-1561.
36. Doitsh G, Cavrois M, Lassen KG, et al. Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue. Cell 2010; 143:789-801.
37. Bull ME, Learn GH, McElhone S, et al. Monotypic human immunodeficiency virus type 1 genotypes across the uterine cervix and in blood suggest proliferation of cells with provirus. J Virol 2009; 83:6020-6028.
38. Carr JM, Cheney KM, Coolen C, et al. Development of methods for coordinate measurement of total cell-associated and integrated human immunodeficiency virus type 1 (HIV-1) DNA forms in routine clinical samples: levels are not associated with clinical parameters, but low levels of integrated HIV-1 DNA may be prognostic for continued successful therapy. J Clin Microbiol 2007; 45:1288-1297. (Pubitemid 46626500)
39. Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med 2008; 148:728-736. (Pubitemid 351717418)
40. Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med 2010; 207:2175-2186.
41. Jin HT, Anderson AC, Tan WG, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A 2010; 107:14733-14738.
42. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 2010; 207:2187-2194.