Article information
Abstract
This review will summarize the role of integrase in HIV-1 infection, the mechanism of integrase inhibitors and resistance with an emphasis on raltegravir (RAL), the first integrase inhibitor licensed to treat HIV-1 infection.
Keywords:
antiretrovirals
integrase inhibitors
raltegravir
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References
[1.]
P. Cahn, O. Sued.
Raltegravir: a new antiretroviral class for salvage therapy.
Lancet, 369 (2007), pp. 1235-1236
[2.]
Brown PO. Retroviruses. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, New York, 1998.
[3.]
T.K. Chiu, D.R. Davies.
Structure and function of HIV-1 integrase.
Curr Top Med Chem, 4 (2004), pp. 965-977
[4.]
R. Craigie.
HIV integrase, a brief overview from chemistry to therapeutics.
J Biol Chem, 276 (2001), pp. 23213-23216
[5.]
A. Engelman, K. Mizuuchi, R. Craigie.
HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer.
Cell, 67 (1991), pp. 1211-1221
[6.]
S.D. Young.
Inhibition of HIV-1 integrase by small molecules: the potential for a new class of AIDS chemotherapeutics.
Curr Opin Drug Discov Devel, 4 (2001), pp. 402-410
[7.]
A.A. Johnson, C. Marchand, Y. Pommier.
HIV-1 integrase inhibitors: a decade of research and two drugs in clinical trial.
Curr Top Med Chem, 4 (2004), pp. 1059-1077
[8.]
Y. Pommier, A.A. Johnson, C. Marchand.
Integrase inhibitors to treat HIV/AIDS.
Nat Rev Drug Discov, 4 (2005), pp. 236-248
[9.]
M. Stevenson, T.L. Stanwick, M.P. Dempsey, C.A. Lamonica.
HIV-1 replication is controlled at the level of T cell activation and proviral integration.
Embo J, 9 (1990), pp. 1551-1560
[10.]
M. Wiskerchen, M.A. Muesing.
Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells.
J Virol, 69 (1995), pp. 376-386
[11.]
D.J. Hazuda, P. Felock, M. Witmer, et al.
Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells.
Science, 287 (2000), pp. 646-650
[12.]
M. Buzón, M. Massanella, J.M. Llibre, et al.
HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects.
Nature Medicine, 16 (2010), pp. 460-465
[13.]
A.S. Espeseth, P. Felock, A. Wolfe, et al.
HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase.
Proc Natl Acad Sci USA, 97 (2000), pp. 11244-11249
[14.]
J.A. Grobler, K. Stillmock, B. Hu, et al.
Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes.
Proc Natl Acad Sci USA, 99 (2002), pp. 6661-6666
[15.]
S. Hare, S.S. Gupta, E. Volkov, A. Engelman, P. Cherepanov.
Retroviral intasome assembly and inhibition of DNA strand transfer.
Nature, 464 (2010), pp. 232-236
[16.]
S. Maignan, J.P. Guilloteau, Q. Zhou-Liu, C. Clement-Mella, V. Mikol.
Crystal structures of the catalytic domain of HIV-1 integrase free and complexed with its metal cofactor: high level of similarity of the active site with other viral integrases.
J Mol Biol, 282 (1998), pp. 359-368
[17.]
F. Damond, S. Lariven, B. Roquebert, et al.
Virological and immunological response to HAART regimen containing integrase inhibitors in HIV-2-infected patients.
AIDS, 22 (2008), pp. 665-666
[18.]
Danovich R, Ke Y, Wan H et al. Raltegravir has similar in vitro antiviral potency, clinical efficacy, and resistance patterns in B subtype and non-B subtype HIV-1. In: Abstracts of the Seventeenth International AIDS Conference, Mexico City, 2008. Abstract TUAA0302.
[19.]
N. Garrett, L. Xu, E. Smit, B. Ferns, S. El-Gadi, J. Anderson.
Raltegravir treatment response in an HIV-2 infected patient: a case report.
AIDS, 22 (2008), pp. 1091-1112
[20.]
K. Shimura, E. Kodama, Y. Sakagami, et al.
Broad antiretroviral activity and resistance profile of the novel HIV integrase inhibitor elvitegravir. (JTK-303/GS-9137).
J Virol, 82 (2008), pp. 764-774
[21.]
V. Briz, C. Garrido, E. Poveda, et al.
Raltegravir and etravirine are active against HIV type 1 group O.
AIDS Res Hum Retroviruses, 25 (2009), pp. 225-227
[22.]
I. Singh, J. Gorzynski, D. Drobysheva, L. Bassit, R. Schinazi.
Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.
PLoS One, 5 (2010), pp. e9948
[23.]
Fransen S, Gupta S, Paxinos E et al. Natural variation in susceptibility of patient-derived HIV-1 to an integrase strand transfer inhibitor. XV International HIV Drug Resistance Workshop: Basic Principles and Clinical Implications; 2006.
[24.]
R.E. Myers, D. Pillay.
Analysis of natural sequence variation and covariation in human immunodeficiency virus type-1 integrase.
J Virol, 82 (2008), pp. 9228-9235
[25.]
A. Low, N. Prada, M. Topper, et al.
Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors.
Antimicrob Agents Chemother, 53 (2009), pp. 4275-4282
[26.]
K. Van Baelen, V. Van Eygen, E. Rondelez, L.J. Stuyver.
Cladespecific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility.
AIDS, 22 (2008), pp. 1877-1880
[27.]
D.J. Hazuda, N.J. Anthony, R.P. Gomez, et al.
From the Cover: A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase.
Proc Natl Acad Sci USA, 101 (2004), pp. 11233-11238
[28.]
O. Goethals, R. Clayton, M. Van Ginderen, et al.
Resistance mutations in HIV type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors.
J Virol, 82 (2008), pp. 10366-10374
[29.]
J. Marinello, C. Marchand, B. Mott, A. Bain, C.J. Thomas, Y. Pommier.
Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants.
Biochemistry, 47 (2008), pp. 9345-9354
[30.]
V. Fikkert, B. Van Maele, J. Vercammen, et al.
Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations.
J Virol, 77 (2003), pp. 11459-11470
[31.]
V. Fikkert, A. Hombrouck, B. Van Remoortel, et al.
Multiple mutations in human immunodeficiency virus-1 integrase confer resistance to the clinical trial drug S-1360.
AIDS, 18 (2004), pp. 2019-2028
[32.]
Jones G, Ledford R, Yu F, Miller MD, et al. Resistance profile of HIV-1 mutants in vitro selected by the HIV-1 integrase inhibitor, GS-9137 (JTK-303). 14th Conference on Retroviruses and Opportunistic Infections Los Angeles. 2007.
[33.]
McColl D, Fransen S, Gupta S et al. Resistance and cross-resistance to first generation integrase inhibitors: insights from a Phase II study of elvitegravir (GS-9137). XVI International HIV Drug Resistance Workshop: Abstract 12. 2007.
[34.]
Ceccherini-Silberstein F, Armenia D, D’Arrigo R et al. Virological response and resistance in multi-experienced patients treated with raltegravir. XVII International HIV Drug Resistance Workshop. Abstract 18. 2008.
[35.]
E.P. Garvey, B.A. Johns, M.J. Gartland, et al.
The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral.
Antimicrob Agents Chemother, 52 (2008), pp. 901-908
[36.]
A. Hombrouck, A. Voet, B. Van Remoortel, et al.
Mutations in human immunodeficiency virus type 1 integrase confer resistance to the naphthyridine L-870,810 and cross-resistance to the clinical trial drug GS-9137.
Antimicrob Agents Chemother, 52 (2008), pp. 2069-2078
[37.]
I. Malet, O. Delelis, M.A. Valantin, et al.
Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro.
Antimicrob Agents Chemother, 52 (2008), pp. 1351-1358
[38.]
D. Cooper, R. Steigbigel, J. Gatell, et al.
Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection.
N Engl J Med, 359 (2008), pp. 355-365
[39.]
C. Charpentier, M. Karmochkine, D. Laureillard, et al.
Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy.
HIV Med, 9 (2008), pp. 765-770
[40.]
S. Fransen, S. Gupta, R. Danovich, et al.
Loss of raltegravir susceptibility of HIV-1 is conferred by multiple non-overlapping genetic pathways.
J. Virol, 83 (2009), pp. 11440-11446
[41.]
H. Hatano, H. Lampiris, S. Fransen, et al.
Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy.
J Acquir Immune Defic Syndr, 54 (2010), pp. 389-393
[42.]
Geretti A, Fearnhill E, Ceccherini-Silberstein F et al. Prevalence and patterns of raltegravir resistance in treated patients in Europe. 2010 XVIV International HIV Drug Resistance Workshop.
[43.]
R. Quercia, E. Dam, D. Perez-Bercoff, F. Clavel.
Selective-advantage profile of Human Immunodeficiency virus type 1 integrase mutants explains In Vivo evolution of raltegravir resistance genotypes.
J.Virol, 83 (2009), pp. 10245-10249
[44.]
Soriano V, Garido C, Alverez E et al. Plasma raltegravir exposure influences the antiviral activity and selection of resistance mutations. 2010 International HIV and Hepatitis Virus Drug Resistance Workshop, Dubrovnik, Croatia.
[45.]
R. Ferns, S. Kirk, J. Bennett, et al.
The dynamics of appearance and disappearance of HIV-1 integrase mutations during and after withdrawal of raltegravir therapy.
AIDS, 23 (2009), pp. 2159-2164
[46.]
C. Garrido, A. Geretti, N. Zahonero, et al.
Integrase variability and susceptibility to HIV integrase inhibitors: impact of subtypes, antiretroviral experience and duration of HIV infection.
J Antimicrob Chemother, 65 (2010), pp. 320-326
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