Effect of raltegravir intensification on HIV proviral DNA in the blood and gut mucosa of men on long-term therapy: A randomized controlled trial

AIDS

Volumn 26, Issue 2, 2012, Pages 167-174

  Chege, Duncan ^a   Kovacs, Colin ^a,c   La Porte, Charles ^d   Ostrowski, Mario ^a,b,e,f   Raboud, Janet ^a,e,g   Su, Desheng ^e,g   Kandel, Gabor ^a,e,f   Brunetta, Jason ^c   Kim, Connie J ^a   Sheth, Prameet M ^a   Kaul, Rupert ^a,b,e,g   Loutfy, Mona R ^a,b,e,f  

^a Department of Medicine ^*  (United States)

^b UNIVERSITY OF TORONTO   (Canada)

^c MAPLE LEAF MEDICAL CLINIC   (Canada)

^d OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^e WOMEN S COLLEGE HOSPITAL   (Canada)

^f ST MICHAEL'S HOSPITAL   (Canada)

^g UNIVERSITY HEALTH NETWORK   (Canada)

Author keywords

blood CD4 + T cell; gut; gut associated lymphoid tissue; HIV; mucosa; proviral DNA; raltegravir; randomized controlled trial; sigmoid

Indexed keywords

PLACEBO; RALTEGRAVIR; VIRUS DNA;

ADULT; ARTICLE; BLOOD; CD4+ T LYMPHOCYTE; CLINICAL ARTICLE; COLON BIOPSY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; INTESTINE MUCOSA; LONG TERM CARE; LYMPHOCYTE COUNT; MALE; PRIORITY JOURNAL; PROVIRUS; RANDOMIZED CONTROLLED TRIAL; SIGMOID; TREATMENT DURATION; VIRUS LOAD;

ADULT; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; DNA, VIRAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; INTESTINAL MUCOSA; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; PROVIRUSES; PYRROLIDINONES; VIRAL LOAD; VIREMIA;

EID: 84155165636     PISSN: 02699370     EISSN: 14735571     Source Type: Journal    
DOI: 10.1097/QAD.0b013e32834e8955     Document Type: Article

References (34)

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. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373:123-126.
3. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 1997; 278:1291-1295.
4. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 1997; 94:13193-13197.
5. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 1997; 278:1295-1300.
6. Chun TW, Nickle DC, Justement JS, Meyers JH, Roby G, Hallahan CW, et al. Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 2008; 197:714-720.
7. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4R T cells. Nature Medicine 2003; 9:727-728.
8. Tobin NH, Learn GH, Holte SE, Wang Y, Melvin AJ, McKernan JL, et al. Evidence that low-level viremias during effective highly active antiretroviral therapy result from two processes: expression of archival virus and replication of virus. J Virology 2005; 79:9625-9634.
9. Coiras M, Lopez-Huertas MR, Perez-Olmeda M, Alcami J. Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nature reviews. Microbiology 2009; 7:798-812.
10. Ramratnam B, Ribeiro R, He T, Chung C, Simon V, Vanderhoeven J, 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.
11. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, et al. Latent infection of CD4R T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999; 5:512-517.
12. Sigal A, Kim JT, Balazs AB, Dekel E, Mayo A, Milo R, et al. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature 2011; 477:95-98.
13. Chun TW, Justement JS, Moir S, Hallahan CW, Maenza J, Mullins JI, et al. Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: implications for eradication of virus. J Infect Dis 2007; 195:1762-1764.
14. Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet 2009; 374:796-806.
15. Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, et al. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Deficy Syndr 2007; 46:125-133.
16. Murray JM, Emery S, Kelleher AD, Law M, Chen J, Hazuda DJ, et al. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS 2007; 21:2315-2321.
17. Buzon MJ, Massanella M, Llibre JM, Esteve A, Dahl V, Puertas MC, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 2010; 16:460-465.
18. 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.
19. 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 1-11.
20. Hatano H, Hayes TL, Dahl V, Sinclair E, Lee TH, 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.
21. Reinhart TA, Rogan MJ, Huddleston D, Rausch DM, Eiden LE, Haase AT. Simian immunodeficiency virus burden in tissues and cellular compartments during clinical latency and AIDS. J Infect Dis 1997; 176:1198-1208.
22. Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, et al. Gastrointestinal tract as a major site of CD4R T cell depletion and viral replication in SIV infection. Science 1998; 280:427-431.
23. Guadalupe M, Reay E, Sankaran S, Prindiville T, Flamm J, McNeil A, et al. Severe CD4R T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol 2003; 77:11708-11717.
24. Yukl SA, Shergill AK, McQuaid K, Gianella S, Lampiris H, Hare CB, 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.
25. Chege D, Sheth PM, Kain T, Kim CJ, Kovacs C, Loutfy M, et al. Sigmoid Th17 populations, the HIV latent reservoir, and microbial translocation in men on long-term antiretroviral therapy. AIDS 2011; 25:741-749.
26. Lorello G, la Porte C, Pilon R, Zhang G, Karnauchow T, MacPherson P. Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma. HIV Med 2009; 10:548-554.
27. Di Mascio M, Dornadula G, Zhang H, Sullivan J, Xu Y, Kulkosky J, et al. In a subset of subjects on highly active antiretroviral therapy, human immunodeficiency virus type 1 RNA in plasma decays from 50 to <5 copies per milliliter, with a half-life of 6 months. J Virol 2003; 77:2271-2275
28. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 1995; 373:117-122.
29. Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Nat Acad Sci U S A 2008; 105:3879-3884.
30. Croxtall JD, Keam SJ. Raltegravir: a review of its use in the management of HIV infection in treatment-experienced patients. Drugs 2009; 69:1059-1075.
31. Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008; 359:355-365.
32. Canducci F, Sampaolo M, Marinozzi MC, Boeri E, Spagnuolo V, Galli A, et al. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS 2009; 23:455-460.
33. Charpentier C, Karmochkine M, Laureillard D, Tisserand P, Belec L, Weiss L, et al. Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy. HIV Med 2008; 9:765-770.
34. Ferns RB, Kirk S, Bennett J, Williams I, Edwards S, Pillay D. The dynamics of appearance and disappearance of HIV-1 integrase mutations during and after withdrawal of raltegravir therapy. AIDS 2009; 23:2159-2164.