L. Pierre, . Physiologie, . Orthopédie, L. Maintien-À-domicile-isabelle, L. Pharmacologie-cardiovasculaire-dominique et al., Chimie physique générale, Chimie thérapeutique Bertrand RIHN .................................. Biochimie

B. Sandrine, B. Mariette, B. Biologie-cellulaire-emmanuelle, . Communication, B. Santé-isabelle et al., Chimie thérapeutique Chimie thérapeutique

B. Ariane, B. Cédric, C. Jean-claude, C. Chimie-générale-et-minérale-igor, C. Chimie-analytique-joël et al., Chimie thérapeutique, Microbiologie clinique Béatrice FAIVRE ??????????????..Hématologie -Génie Biologique

J. Olivier, . Toxicologie, K. Sécurité-sanitaire-francine, L. Pharmacie-galénique-alexandrine, B. Informatique et al., Chimie organique Biophysique

S. Anne, S. Pharmacie-galénique-marie-paule, B. Mycologie, T. Nathalie, T. Santé-publique-gabriel et al., Pharmacie galénique 3, Biochimie et Biologie, vol.1, issue.1

G. Muirhead, Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers, Br J Clin Pharmacol, vol.65, pp.5-18, 2008.

G. Allison, M. Bostrom, and M. Glesby, Osteonecrosis in HIV disease, AIDS, vol.17, issue.1, pp.1-9, 2003.
DOI : 10.1097/00002030-200301030-00003

V. Amorosa and P. Tebas, Bone disease and HIV infection, Clin Infect Dis, vol.42, pp.108-122, 2006.

X. Anglaret, . Vih, and . Sida-dans-le-monde, VIH/sida dans le monde??: de l?????pid??miologie au traitement universel, La Revue de M??decine Interne, vol.29, pp.269-73, 2008.
DOI : 10.1016/j.revmed.2008.10.002

Y. Ariumi, F. Sherhan, P. Turelli, A. Telenti, and D. Trono, The integrase interactor 1(IN1) proteins facilitate Tat-mediated human immunodeficiency virus type 1 transcription

J. Arnsten, R. Freeman, and A. Howard, HIV Infection and Bone Mineral Density in Middle-Aged Women, Clinical Infectious Diseases, vol.81, issue.8, pp.1014-1034, 2006.
DOI : 10.1210/jc.81.8.2948

URL : https://academic.oup.com/cid/article-pdf/42/7/1014/915442/42-7-1014.pdf

M. Benkirane, D. Jin, R. Chun, R. Koup, and K. Jeang, Mechanism of Transdominant Inhibition of CCR5-mediated HIV-1 Infection by ccr5??32, Journal of Biological Chemistry, vol.66, issue.49, pp.30603-30609, 1997.
DOI : 10.1093/nar/25.2.379

R. Berro, R. Sanders, M. Lu, P. Klasse, and J. Moore, Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry, PLoS Pathogens, vol.13, issue.8, pp.10548-55, 2009.
DOI : 10.1371/journal.ppat.1000548.s004

J. Buxeraud, Isentress-raltégravir. Fiche médicaments sortant de la réserve hospitalière, Actualités pharmaceutiques, vol.483, pp.55-61, 2009.
DOI : 10.1016/s0515-3700(09)70340-4

M. Caron, M. Auclair, and A. Vissian, Contribution of mitochondrial dysfunction and oxidative stress to cellular premature senescence induced by antiretroviral thymidine analogues, Antivir Ther, vol.13, pp.27-38, 2008.

C. Cazanavea, M. Dupona, and V. Lavignolle-aurillac, Reduced bone mineral density in HIV-infected patients: prevalence and associated factors, AIDS, vol.22, issue.3, pp.395-402, 2008.
DOI : 10.1097/QAD.0b013e3282f423dd

M. Chaix, J. Fichou, and C. Deveau, Stable frequency of HIV-1 transmitted drug resistance mutation over a decade (1996-2006) in France is likely explained by the increase of chronically treated patients in virological success, Antivir Ther, vol.12, p.49, 2007.

P. Cherepanov, E. Devroe, P. Silver, and A. Engelman, Identification of an Evolutionarily Conserved Domain in Human Lens Epithelium-derived Growth Factor/Transcriptional Co-activator p75 (LEDGF/p75) That Binds HIV-1 Integrase, Journal of Biological Chemistry, vol.73, issue.47, pp.48883-92, 2004.
DOI : 10.1093/bioinformatics/15.4.305

C. Chidiac, C. Katlama, and P. Yéni, Maraviroc : r??sultats des ??tudes cliniques, M??decine et Maladies Infectieuses, vol.38, pp.17-23, 2008.
DOI : 10.1016/S0399-077X(08)70540-7

T. Chiu and D. Davies, Structure and Function of HIV-1 Integrase, Current Topics in Medicinal Chemistry, vol.4, issue.9, pp.965-77, 2004.
DOI : 10.2174/1568026043388547

L. Cooley and S. Lewin, HIV-1 cell entry and advances in viral entry inhibitor therapy, Journal of Clinical Virology, vol.26, issue.2, pp.2228-2266, 2003.
DOI : 10.1016/S1386-6532(02)00111-7

D. Cooper, R. Steigbigel, J. Gatell, J. Rockstroh, C. Katlama et al., Subgroup and Resistance Analyses of Raltegravir for Resistant HIV-1 Infection, New England Journal of Medicine, vol.359, issue.4, pp.339-54, 2008.
DOI : 10.1056/NEJMoa0708978

P. L. Corbeau, impact du niveau d'expression du corécepteur CCR5 sur l'histoire naturelle de l'infection par VIH, Virologie, vol.10, issue.4, pp.279-86, 2006.

D. Costagliola, ??pid??miologie de l???infection ?? VIH en France et en Europe, La Revue de M??decine Interne, vol.29, pp.266-68, 2008.
DOI : 10.1016/j.revmed.2008.10.004

R. Craigie, HIV Integrase, a Brief Overview from Chemistry to Therapeutics, Journal of Biological Chemistry, vol.69, issue.26, pp.23213-23219, 2001.
DOI : 10.1016/0263-7855(87)80010-3

A. Cribier and S. Emiliani, Les partenaires cellulaires de l'intégrase du VIH-1 : vers de nouvelles cibles thérapeutiques, Virologie, vol.11, pp.153-62, 2007.

J. Croxtall, K. Lyseng-williamson, and P. C. Raltégravir, Raltegravir, Drugs, vol.43, issue.5, pp.131-139, 2008.
DOI : 10.2165/00003495-200868010-00009

A. Eberhard, B. Ponceau, F. Biron, and B. Verrier, Les mécanismes de résistance à la transmission sexuelle du VIH-1. Médecines et maladies infectieuses, pp.517-541, 2005.
DOI : 10.1016/j.medmal.2005.09.003

C. Emile, Le maraviroc, un nouvel antirétroviral qui nécessite un test biologique, OptionBio, vol.412, 2009.

A. Engelmann and R. Craigie, Efficient magnesium-dependent human immunodeficiency virus type 1 integrase activity, J Virol, vol.69, pp.5908-911, 1995.

D. Esposito and R. Craigie, Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interaction, The EMBO Journal, vol.17, issue.19, pp.5832-5875, 1998.
DOI : 10.1093/emboj/17.19.5832

G. Fätkenheuer, A. Pozniak, M. Jonhson, A. Plettenberg, S. Stazewski et al., Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1, Nature Medicine, vol.19, issue.11, pp.1170-1172, 2005.
DOI : 10.1097/01.aids.0000183633.06580.8a

B. Grinsztejn, B. Nguyen, and C. Katlama, Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial, The Lancet, vol.369, issue.9569, pp.1261-1270, 2007.
DOI : 10.1016/S0140-6736(07)60597-2

R. Gulik, H. Ribodau, and C. Shikuma, Triple-Nucleoside Regimens versus Efavirenz-Containing Regimens for the Initial Treatment of HIV-1 Infection, New England Journal of Medicine, vol.350, issue.18, pp.1850-61, 2004.
DOI : 10.1056/NEJMoa031772

M. Hirsch, F. Brun-Ézinet, and B. Clotet, Antiretroviral drug resistance testing in adult HIV-1 infection: 2003 recommandations of an International AIDS-society-USA panel, Clin Infect Dis, vol.37, pp.1722-1725, 2003.

S. Mclaughlin, R. Shankarappa, J. Margolick, and J. Mullins, Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences, Journal of Virology, vol.77, issue.24, pp.13376-88, 2003.

K. Kassahun, I. Mclntosh, and G. D. , Metabolism and Disposition in Humans of Raltegravir (MK-0518), an Anti-AIDS Drug Targeting the Human Immunodeficiency Virus 1 Integrase Enzyme, Drug Metabolism and Disposition, vol.35, issue.9, pp.1657-63, 2007.
DOI : 10.1124/dmd.107.016196

C. Katlama, R. Tubiana, and R. Murphy, Les nouvelles mol??cules anti-VIH??: la place du ralt??gravir, Antibiotiques, vol.11, issue.1, pp.11-18, 2009.
DOI : 10.1016/j.antib.2008.12.001

D. Kuritzkes, J. Jacobson, W. Powderly, E. Godofsky, E. Dejesus et al., Antiretroviral Activity of the Anti???CD4 Monoclonal Antibody TNX???355 in Patients Infected with HIV Type 1, The Journal of Infectious Diseases, vol.189, issue.2, pp.286-91, 2004.
DOI : 10.1086/380802

B. Lader, G. Darby, and D. Richmann, HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy, Science, vol.243, issue.4899, pp.1731-1765, 1989.
DOI : 10.1126/science.2467383

C. Lagathu, B. Eustace, and M. Prot, Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages

O. Launay, Th??rapeutiques antir??trovirales??: principes du traitement de l???infection par le VIH, La Presse M??dicale, vol.37, issue.6
DOI : 10.1016/j.lpm.2007.10.016

M. Ledermann, A. Penne-nicholson, M. Cho, and D. Mosier, Biology of CCR5 and Its Role in HIV Infection and Treatment, JAMA, vol.296, issue.7, pp.815-841, 2006.
DOI : 10.1001/jama.296.7.815

J. Lefrère, Les virus transmissibles par le sang, 1996.

C. Leporte, P. Longuet, A. Gervais, and J. Vildé, Manifestations cliniques de l'infection par le virus de l'immunodéficience humaine. Editions Scientifiques et Médicales, 2002.

J. Lennox, E. Dejesus, and A. Lazzarin, 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, The Lancet, vol.374, issue.9692, pp.796-806, 2009.
DOI : 10.1016/S0140-6736(09)60918-1

A. Levin, J. Rosenbluh, Z. Hayouka, A. Friedler, and A. Loyter, Integration of HIV-1 DNA is regulated by interplay between viral Rev and cellular LEDGF/p75 proteins, Mol Med, vol.16, issue.12, pp.34-44, 2009.

C. Lewden, T. May, and E. Rosenthal, Changes in Causes of Death Among Adults Infected by HIV Between 2000 and 2005: The ???Mortalit?? 2000 and 2005??? Surveys (ANRS EN19 and Mortavic), JAIDS Journal of Acquired Immune Deficiency Syndromes, vol.48, issue.5, pp.590-98, 2008.
DOI : 10.1097/QAI.0b013e31817efb54

M. Lewinski and S. Bushmann, Retroviral DNA Integration???Mechanism and Consequences, Adv Genet, vol.55, pp.147-181, 2005.
DOI : 10.1016/S0065-2660(05)55005-3

P. Lorenzi, M. Opravil, and B. Hirshel, Impact of drug resistance mutations on virologic response to salvage therapy, AIDS, vol.13, issue.2, pp.17-21, 1999.
DOI : 10.1097/00002030-199902040-00001

A. Llyod, S. Tateishi, P. Bieniasz, M. Muesing, M. Yamaizumi et al., Effect of DNA repair protein rad 18 on viral infection, PLoS Pathog, vol.2, pp.1-40, 2006.

V. Mallet, P. Blanchard, and V. Verkarre, Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients, AIDS, vol.21, issue.2, pp.187-92, 2007.
DOI : 10.1097/QAD.0b013e3280119e47

M. Markowitz, B. Nguyen, and E. Gotuzzo, 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, JAIDS Journal of Acquired Immune Deficiency Syndromes, vol.46, issue.2, pp.125-158, 2007.
DOI : 10.1097/QAI.0b013e318157131c

S. Martin, D. Burton, and I. Roitt, Fondements de l'immunologie. Edition de Boeck Université. Traduction de la 11 ème édition anglaise du Roitt's essential immunology. 465 p Merck and Co. Mentions obligatoires complètes, 2008.

V. Merluzzi, K. Hargrave, M. Labadia, K. Grozinger, M. Skoog et al., Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor, Science, vol.250, issue.4986, pp.1411-1424, 1990.
DOI : 10.1126/science.1701568

K. Mondy, K. Yarashesky, and W. Powderly, Longitudinal Evolution of Bone Mineral Density and Bone Markers in Human Immunodeficiency Virus???Infected Individuals, Clinical Infectious Diseases, vol.5, issue.4, pp.482-90, 2003.
DOI : 10.1210/jc.84.6.1932

J. Moore and R. Doms, The entry of entry inhibitors: A fusion of science and medicine, Proceedings of the National Academy of Sciences, vol.46, issue.5, pp.10598-602, 2003.
DOI : 10.1128/AAC.46.5.1336-1339.2002

A. Morozov, E. Yung, and G. Kaplana, Structure-function analysis of integrase interactor 1/hSNF5L1 reveals differential properties of two repeat motifs present in the highly conserved region, Proceedings of the National Academy of Sciences, vol.379, issue.6568, pp.1120-1125, 1998.
DOI : 10.1038/379844a0

J. Mouscadet, L. Tchertanov, and E. Deprez, Structures et rôles de l'intégrase du VIH dans le cycle viral, Virologie, vol.11, pp.143-52, 2007.

C. Orkin, J. Stebbing, and M. Nelson, A randomized study comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study), Journal of Antimicrobial Chemotherapy, vol.55, issue.2, pp.246-55, 2005.
DOI : 10.2165/00003088-200241010-00001

K. Pandey and D. Grandgenett, HIV-1 integrase strand transfer inhibitors: novel insights into their mechanism of action, Retrovirology, vol.2, pp.11-17, 2008.

N. Paton, D. Macallan, G. Griffin, and M. Pazianas, Bone Mineral Density in Patients with Human Immunodeficiency Virus Infection, Calcified Tissue International, vol.61, issue.1, pp.30-32, 1997.
DOI : 10.1007/s002239900288

G. Peytavin, Pharmacocin??tique clinique du maraviroc Clinical pharmacokinetic of maraviroc, M??decine et Maladies Infectieuses, vol.38, pp.12-18, 2008.
DOI : 10.1016/S0399-077X(08)70539-0

Y. Pommier, A. Johnson, and C. Marchand, Integrase inhibitors to treat HIV/Aids, Nature Reviews Drug Discovery, vol.17, issue.3, pp.236-284, 2005.
DOI : 10.1038/9886

T. Porco, J. Martin, and K. Page-shafer, Decline in HIV infectivity following the introduction of highly active antiretroviral therapy, AIDS, vol.18, issue.1, pp.81-89, 2004.
DOI : 10.1097/00002030-200401020-00010

P. Pugach, A. Marozsan, T. Ketas, E. Landes, J. Moore et al., HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry, Virology, vol.361, issue.1
DOI : 10.1016/j.virol.2006.11.004

J. Reynes, Inhibiteurs du CCR5: développement clinique et perspectives thérapeutiques antirétrovirales, Virologie, vol.11, pp.120-129, 2007.

D. Richmann, S. Morton, and T. Wrin, The prevalence of antiretroviral drug resistance in the United States, AIDS, vol.18, issue.10, pp.1393-401, 2004.
DOI : 10.1097/01.aids.0000131310.52526.c7

B. Roquebert, F. Damond, F. Brun-vézinet, and D. Descamps, Diversit?? g??n??tique des VIH et ses cons??quences, Pathologie Biologie, vol.57, issue.2, pp.142-148, 2008.
DOI : 10.1016/j.patbio.2008.04.004

M. Saag, I. Prudence, and J. Heera, A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine for the treatment of antiretroviral naive patients infected with R5 HIV 1: week 48 results of the MERIT study, IAS) Conference on HIV Pathogenesis, Treatment and Prevention, 2007.

M. Saag, J. Heera, and J. Goodrich, Reanalysis of the MERIT study with the enhanced Trofile assay, 48th International Conference on Antimicrobial Agents and Chemotherapy, 2008.

C. Soulié and V. Calvez, Tests de tropisme du VIH à l'heure de la mise à disposition du 1 er

X. Tribonnière, Y. Yazdanpanah, and J. Reynes, Les inhibiteurs de CCR5 : une nouvelle classe d???antir??troviraux, M??decine et Maladies Infectieuses, vol.38, pp.1-6, 2008.
DOI : 10.1016/S0399-077X(08)70537-7

F. Tsamis, S. Gavrilov, F. Kajumo, C. Seibert, S. Kuhmann et al., Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125, p.350581

R. Tubiana, Les résultats des essais cliniques concernant les inhibiteurs de l'intégrase du VIH, Virologie, vol.11, pp.183-92, 2007.

M. Wainberg and K. Jeang, 25 years of HIV-1 research ??? progress and perspectives, BMC Medicine, vol.3, issue.1, p.31, 2008.
DOI : 10.1186/1742-4690-3-87

D. Walker, S. Abel, P. Comby, A. Nedderman, and D. Smith, SPECIES DIFFERENCES IN THE DISPOSITION OF THE CCR5 ANTAGONIST, UK-427,857, A NEW POTENTIAL TREATMENT FOR HIV, Drug Metabolism and Disposition, vol.33, issue.4, pp.587-95, 2005.
DOI : 10.1124/dmd.104.002626

J. Whitcomb, W. Huang, S. Fransen, K. Limoli, J. Toma et al., Development and Characterization of a Novel Single-Cycle Recombinant-Virus Assay To Determine Human Immunodeficiency Virus Type 1 Coreceptor Tropism, Antimicrobial Agents and Chemotherapy, vol.51, issue.2, pp.566-75, 2007.
DOI : 10.1128/AAC.00853-06

J. Wielens, I. Crosby, and D. Charmers, A Three-dimensional Model of the Human Immunodeficiency Virus Type 1 Integration Complex, Journal of Computer-Aided Molecular Design, vol.76, issue.5, pp.301-318, 2005.
DOI : 10.1080/07391102.1998.10508285

S. Wolinsky, R. Veazey, K. Kunstman, P. Klasse, J. Dufour et al., Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses, Virology, vol.328, issue.1, pp.19-29, 2004.
DOI : 10.1016/j.virol.2004.07.021

T. Yamashita, J. Phair, and A. Munoz, Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study, AIDS, vol.15, issue.6, pp.735-781, 2001.
DOI : 10.1097/00002030-200104130-00009

P. Yéni, Prise en charge médicale des personnes infectées par le VIH, rapport 2008, recommandations du groupe d'experts. Edition Paris Flammarion médecine-sciences, 2008.

E. Yung, M. Sorin, and A. Pal, Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1, Nature Medicine, vol.22, issue.8, pp.920-926, 2001.
DOI : 10.1038/8811

Y. Zhou, A. Kottmann, M. Kuroda, I. Taniuchi, and D. Littmann, Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development, Nature, vol.140, issue.6685, pp.595-604, 1998.
DOI : 10.1007/BF00267823