Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy

Clinical Infectious Diseases

Volumn 50, Issue 6, 2010, Pages 912-919

  McMahon, D ^a   Jones, J ^a   Wiegand, A ^b   Gange, S J ^c   Kearney, M ^b   Palmer, S ^b,f   McNulty, S ^a   Metcalf, J A ^d   Acosta, E ^e   Rehm, C ^d   Coffin, J M ^b   Mellors, J W ^a   Maldarelli, F ^b  

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

^b NATIONAL CANCER INSTITUTE   (United States)

^c JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

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

^e University of Alabama at Birmingham   (United States)

^f KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; EFAVIRENZ; EMTRICITABINE; LAMIVUDINE; LOPINAVIR PLUS RITONAVIR; NEVIRAPINE; RALTEGRAVIR; TENOFOVIR; VIRUS RNA;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DRUG EFFECT; DRUG EFFICACY; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MALE; PRIORITY JOURNAL; SHORT COURSE THERAPY; VIREMIA; VIRUS REPLICATION;

ADULT; AGED; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; PYRROLIDINONES; RNA, VIRAL; VIRAL LOAD; VIREMIA;

EID: 77749277080     PISSN: 10584838     EISSN: None     Source Type: Journal    
DOI: 10.1086/650749     Document Type: Article

References (42)

1. Wong JK, Hezareh M, Gunthard HF, et al. Recovery of replicationcompetent HIV despite prolonged suppression of plasma viremia. Science 1997; 278(5341):1291-1295. (Pubitemid 27495741)
2. Palmer S, Wiegand AP, Maldarelli F, 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 Microbiol 2003; 41(10):4531-4536. (Pubitemid 37259753)
3. Palmer S, Maldarelli F, Wiegand A, et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci USA 2008; 105(10):3879-3884. (Pubitemid 351723493)
4. Maldarelli F, Palmer S, King MS, et al. ART suppresses plasma HIV1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog2007;3(4):c46.
5. Lewin SR, Vesanen M, Kostrikis L, et al. Use of real-time PCR and molecular beacons to detect virus replication in human immunodeficiency virus type 1-infected individuals on prolonged effective antiretroviral therapy. J Virol 1999;73(7):6099-6103. (Pubitemid 29274900)
6. Hermankova. M, Ray SC, Ruff C, et al. HIV-1 drug resistance profiles in children and adults with viral load of <50 copies/mL receiving combination therapy. JAMA 2001;286(2):196-207. (Pubitemid 32640851)
7. Chun TW, Stuyver L, Mizeli SB, et al. Presence of an inducible HIV1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA 1997;94(24):13193-13197. (Pubitemid 27518498)
8. Chun TW, Nickle DC, Justement JS, et al. HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J Clin Invest 2005; 115(11): 3250-3255.
9. Chun TW, Justement JS, Moir S, 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(12):1762-1764. (Pubitemid 46870248)
10. Tobin NH, Learn GH, Holte SE, 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 Virol 2005;79:9625-9634.
11. Shiu C, Cunningham CK, Greenough T, et al. Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. J Virol 2009;83(19):9731-9742.
12. Havlir DV, Strain MC, Clerici M, et al. 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 2003; 77(20):11212-1.1219. (Pubitemid 37204311)
13. 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(l):33-37. (Pubitemid 38044779)
14. Finzi D, Hermankova M, Pierson T, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 1997;278(5341):1295-1300. (Pubitemid 27495742)
15. Chun TW, Fauci AS. Latent reservoirs of HIV: obstacles to the eradication of virus. Proc Natl Acad Sd U S A 1999;96:10958-10961. (Pubitemid 29487311)
16. Finzi D, Blankson J, Siliciano JD, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999; 5(5):512-517. (Pubitemid 29220209)
17. Joos B, Fischer M, Kuster H, et al. HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci USA 2008; 105(43):16725-16730.
18. Varatharajan L, Thomas SA. The transport of anti-HIV drags across blood-CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res 2009;82(2):A99-A109.
19. Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J. Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol 2007; 73 ( 10) : 1573-1581. (Pubitemid 46527547)
20. Shaik N, Giri N, Pan G, Elmquist WF. P-glycoprotein-mediated active efflux of the anti-HIV 1 nucleoside abacavir limits cellular accumulation and brain distribution. Drug Metab Dispos 2007;35(11):2076-2085. (Pubitemid 350005198)
21. Peeters MF, Colebunders RL, Van den Abbeele K, et al. Comparison of human immunodeficiency virus biological phenotypes isolated from cerebrospinal fluid and peripheral blood. J Med Virol 1995;47(1): 92-96.
22. Letendre S, Marquie-Beck J, Capparelli E, et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008;65(l):65-70.
23. Clements JE, Li M, Gama L, et al. The central nervous system is a viral reservoir in simian immunodeficiency virus-infected macaques on combined antiretroviral therapy: a model for human immunodeficiency virus patients on highly active antiretroviral therapy. J Neurovirol2005;11(2):180-189.
24. Best BM, Letendre SL, Brigid E, et al. Low atazanavir concentrations in cerebrospinal fluid. AIDS 2009;23(l):83-87.
25. Wei X, Ghosh SK, Taylor ME, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 1995;373(6510):117-122.
26. Perelson AS, Essunger P, Cao Y, et al. Decay characteristics of HIV-1infected compartments during combination therapy. Nature 1997; 387(6629):188-191. (Pubitemid 27209434)
27. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV1 infection. Nature 1995;373(6510):123-126.
28. Di Mascio M, Dornadula G, Zhang H, 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(3):2271-2275.
29. Dinoso J, 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(23):9403-9408.
30. Murray JM, Emery S, Kelleher AD, et al. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS 2007;21(17):2315-2321. (Pubitemid 350287458)
31. Markowitz M, Nguyen BY, Gotuzzo E, 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 Defic Syndr 2007;46(2):125-133. (Pubitemid 47482607)
32. Markowitz M, Morales-Ramirez JO, Nguyen BY, et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr 2006;43(5):509-515. (Pubitemid 44885615)
33. Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Division of AIDS table for grading the severity of adult and pediatric adverse events December 2004. 2004. http://www3.niaid. nih.gov/labsandresources/resources/DAIDSClinRsrch/Safety.htm. Accessed 5 February 2010.
34. Long MC, Bennetto-Hood C, Acosta EP. A sensitive HPLC-MS-MS method for the determination of raltegravir in human plasma. J Chromatogr B Analyt Technol Biomed Life Sd 2008;867(2):165-171.
35. Hughes JP. Mixed effects models with censored data with application to HIV RNA levels. Biometrics 1999; 55(2):625-629.
36. Thiébaut R, Jacqmin-Gadda H. Mixed models for longitudinal leftcensored repeated measures. Comput Methods Programs Biomed 2004; 74(3):255-260. (Pubitemid 38591637)
37. Iwamoto M, Wenning LA, Petry AS, et al. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther 2008;83(2):293-299.
38. Koelsch KK, Liu L, Haubrich R, et al. Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro. J Infect Dis 2008; 197(3):411-419. (Pubitemid 351263423)
39. Steigbigel RT, Cooper DA, Kumar PN, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008; 359(4):339-354.
40. Wilkin TJ, McKinnon JE, Dirienzo AG, et al. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologie outcomes. J Infect Dis 2009; 199(6): 866-871.
41. Kennedy PE, Bera TK, Wang QC, et al. Anti-HIV-1 ¡mmunotoxin 3B3(Fv)-PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaques. J Leukoc Biol 2006;80(5):1175-1182.
42. Schito ML, Kennedy PE, Kowal RP, Berger EA, Sher A. A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression. J Infect Dis 2001;183(11):1592- 1600.