The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: A randomized controlled trial

PLoS Medicine

Volumn 7, Issue 8, 2010, Pages

  Gandhi, Rajesh T ^a   Zheng, Lu ^b   Bosch, Ronald J ^b   Chan, Ellen S ^b   Margolis, David M ^c   Read, Sarah ^d   Kallungal, Beatrice ^e   Palmer, Sarah ^f   Medvik, Kathy ^g   Lederman, Michael M ^g   Alatrakchi, Nadia ^h   Jacobson, Jeffrey M ⁱ   Wiegand, Ann ^j   Kearney, Mary ^j   Coffin, John M ^k   Mellors, John W ^l   Eron, Joseph J ^c  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c UNIVERSITY OF NORTH CAROLINA   (United States)

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

^e SOCIAL AND SCIENTIFIC SYSTEMS INC   (United States)

^f KAROLINSKA INSTITUTE   (Sweden)

^g CASE WESTERN RESERVE UNIVERSITY   (United States)

^h BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

ⁱ DREXEL UNIVERSITY   (United States)

^j NATIONAL CANCER INSTITUTE   (United States)

^k TUFTS UNIVERSITY   (United States)

^l UNIVERSITY OF PITTSBURGH   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PLACEBO; PROTEINASE INHIBITOR; RALTEGRAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS RNA;

ADULT; ANTIRETROVIRAL THERAPY; ANTIVIRAL THERAPY; ARTICLE; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; ERADICATION THERAPY; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OUTCOME ASSESSMENT; RANDOMIZED CONTROLLED TRIAL; REAL TIME POLYMERASE CHAIN REACTION; T LYMPHOCYTE ACTIVATION; TREATMENT DURATION; VIREMIA; VIRUS DETECTION; VIRUS LOAD; VIRUS REPLICATION;

ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; PYRROLIDINONES; VIRAL LOAD; VIREMIA;

EID: 77956856393     PISSN: 15491277     EISSN: 15491676     Source Type: Journal    
DOI: 10.1371/journal.pmed.1000321     Document Type: Article

References (21)

1. Dornadula G, Zhang H, VanUitert B, Stern J, Livornese L Jr, et al. (1999) Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA 282: 1627-1632.
2. Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, et al. (2007) ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog 3: e46.
3. Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, et al. (2008) Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 105: 3879-3884.
4. Coiras M, Lopez-Huertas MR, Perez-Olmeda M, Alcami J (2009) Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat Rev Microbiol 7: 798-812.
5. Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, et al. (2009) Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A 106: 9403-9408.
6. McMahon D, Jones J, Wiegand A, Gange S, Kearney M, et al. (2010) Short Course Raltegravir Intensification Does Not Reduce Persistent Low Level Viremia in Patients Suppressed on Combination Antiretroviral Therapy. Clin Infect Dis 50: 912-919.
7. Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, et al. (2008) Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 359: 339-354.
8. Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, et al. (2009) 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 374: 796-806.
9. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, et al. (2003) New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 41: 4531-4536.
10. Clement LT, Vink PE, Bradley GE (1990) Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate. J Immunol 145: 102-108.
11. Rabian-Herzog C, Lesage S, Gluckman E (1992) Characterization of lymphocyte subpopulations in cord blood. Bone Marrow Transplant 9 Suppl 1: 64-67.
12. Dianzani U, Funaro A, DiFranco D, Garbarino G, Bragardo M, et al. (1994) Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule. J Immunol 153: 952-959.
13. Havlir DV, Strain MC, Clerici M, Ignacio C, Trabattoni D, et al. (2003) Productive infection maintains a dynamic steady state of residual viremia in human immunodeficiency virus type 1-infected persons treated with suppressive antiretroviral therapy for five years. J Virol 77: 11212-11219.
14. Sedaghat AR, Siliciano JD, Brennan TP, Wilke CO, Siliciano RF (2007) Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART. PLoS Pathog 3: e122.
15. Kieffer TL, Finucane MM, Nettles RE, Quinn TC, Broman KW, et al. (2004) Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults with undetectable HIV loads. J Infect Dis 189: 1452-1465.
16. Buzon MJ, Massanella M, Llibre JM, Esteve A, Dahl V, et al. (2010) HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 16: 460-465.
17. Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, et al. (2003) 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 187: 1534-1543.
18. Goicoechea M, Smith DM, Liu L, May S, Tenorio AR, et al. (2006) Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis 194: 29-37.
19. Gandhi RT, Spritzler J, Chan E, Asmuth DM, Rodriguez B, et al. (2006) Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr 42: 426-434.
20. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, et al. (2009) Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 23: 1059-1067.
21. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, et al. (2009) The challenge of finding a cure for HIV infection. Science 323: 1304-1307.