Authentic HIV-1 Integrase Inhibitors

• Gottlieb MS , SchroffR, Schanker HMet al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N. Engl. J. Med.305(24), 1425–1431 (1981).
   PubMed Web of Science ®Google Scholar
• Masur H , MichelisMA, GreeneJBet al. An outbreak of community–acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N. Engl. J. Med. 305(24), 1431–1438 (1981).
   PubMed Web of Science ®Google Scholar
• Siegal FP , LopezC, HammerGSet al. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N. Engl. J. Med. 305(24), 1439–1444 (1981).
   PubMed Web of Science ®Google Scholar
• Sanders RW , DankersMM, BusserEet al. Evolution of the HIV-1 envelope glycoproteins with a disulfide bond between gp120 and gp41. Retrovirology 1, 3–13 (2004).
   PubMedGoogle Scholar
• Richman DD . HIV chemotherapy.Nature410(6831), 995–1001 (2001).
   PubMed Web of Science ®Google Scholar
• Sarafianos SG , MarchandB, DasKet al. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J. Mol. Biol. 385(3), 693–713 (2009).
   PubMed Web of Science ®Google Scholar
• Anthony NJ . HIV-1 integrase: a target for new AIDS chemotherapeutics.Curr. Top. Med. Chem.4(9), 979–990 (2004).
   PubMed Web of Science ®Google Scholar
• Louis JM , IshimaR, TorchiaDA, WeberIT. HIV-1 protease: structure, dynamics, and inhibition.Adv. Pharmacol.55, 261–298 (2007).
   PubMedGoogle Scholar
• Flexner C . HIV drug development: the next 25 years.Nat. Rev. Drug Discov.6(12), 959–966 (2007).
   PubMed Web of Science ®Google Scholar
• Nikolopoulos G , BonovasS, TsantesA, SitarasNM. HIV/AIDS: recent advances in antiretroviral agents.Mini Rev. Med. Chem.9(8), 900–910 (2009).
   PubMed Web of Science ®Google Scholar
• Li F , Goila-GaurR, SalzwedelKet al. PA–457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc. Natl. Acad. Sci. 100(23), 13555–13560 (2003).
   PubMed Web of Science ®Google Scholar
• Palella FJ Jr, Delaney KM, Moorman AC et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N. Engl. J. Med.338(13), 853–860 (1998).
   PubMed Web of Science ®Google Scholar
• Becker SL , DeziiCM, BurtcelBet al. Young HIV-infected adults are at greater risk for medication nonadherence. MedGenMed. 4(3), 21 (2002).
   PubMedGoogle Scholar
• Anker M , CoralesRB. Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection.Expert Opin. Investig. Drugs17(1), 97–103 (2008).
   PubMed Web of Science ®Google Scholar
• Croxtall JD , KeamSJ. Raltegravir: a review of its use in the management of HIV infection in treatment-experienced patients.Drugs69(8), 1059–1075 (2009).
   PubMed Web of Science ®Google Scholar
• Pommier Y , JohnsonAA, MarchandC. Integrase inhibitors to treat HIV/AIDS.Nat. Rev. Drug Discov.4(3), 236–248 (2005).
   PubMed Web of Science ®Google Scholar
• Savarino A . A historical sketch of the discovery and development of HIV–1 integrase inhibitors.Expert Opin. Investig. Drugs15(12), 1507–1522 (2006).
   PubMed Web of Science ®Google Scholar
• Rice PA , BakerTA. Comparative architecture of transposase and integrase complexes.Nat. Struct. Biol.8(5), 302–307 (2001).
   Google Scholar
• Ramratnam B , MittlerJE, ZhangLet al. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat. Med. 6(1), 82–85 (2000).
   PubMed Web of Science ®Google Scholar
• Marchand C , JohnsonAA, KarkiRGet al. Metal-dependent inhibition of HIV-1 integrase by β-diketo acids and resistance of the soluble double-mutant (F185K/C280S). Mol. Pharmacol. 64(3), 600–609 (2003).
   PubMed Web of Science ®Google Scholar
• Marchand C , NeamatiN, PommierY. In vitro human immunodeficiency virus type 1 integrase assays. Methods Enzymol.340, 624–633 (2001).
   PubMed Web of Science ®Google Scholar
• Liao C , NicklausMC. Tautomerism and magnesium chelation of HIV-1 integrase inhibitors: a theoretical study.ChemMedChem5, 1053–1066 (2010).
   PubMed Web of Science ®Google Scholar
• Debyser Z , CherepanovP, PluymersW, De Clercq E. Assays for the evaluation of HIV-1 integrase inhibitors. Methods Mol. Biol.160, 139–155 (2001).
   PubMedGoogle Scholar
• Sinha S , PursleyMH, GrandgenettDP. Efficient concerted integration by recombinant human immunodeficiency virus type 1 integrase without cellular or viral cofactors.J. Virol.76(7), 3105–3113. (2002).
   PubMed Web of Science ®Google Scholar
• Li M , MizuuchiM, BurkeTR Jr, Craigie R. Retroviral DNA integration: reaction pathway and critical intermediates. EMBO J.25(6), 1295–1304 (2006).
   PubMed Web of Science ®Google Scholar
• Fesen MR , KohnKW, LeteurtreF, PommierY. Inhibitors of human immunodeficiency virus integrase.Proc. Natl Acad. Sci.90(6), 2399–2403 (1993).
   PubMed Web of Science ®Google Scholar
• Chiu TK , DaviesDR. Structure and function of HIV-1 integrase.Curr. Top. Med. Chem.4(9), 965–977 (2004).
   PubMed Web of Science ®Google Scholar
• Semenova EA , JohnsonAA, MarchandCet al. Preferential inhibition of the magnesium-dependent strand transfer reaction of HIV-1 integrase by a-hydroxytropolones. Mol. Pharmacol. 69(4), 1454–1460 (2006).
   PubMed Web of Science ®Google Scholar
• Svarovskaia ES , BarrR, ZhangX, PaisGCet al. Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions. J. Virol. 78(7), 3210–3222 (2004).
   PubMed Web of Science ®Google Scholar
• Marchand C , MaddaliK, MetifiotM, PommierY. HIV-1 IN inhibitors: 2010 update and perspectives.Curr. Top. Med. Chem.9(11), 1016–1037 (2009).
   PubMed Web of Science ®Google Scholar
• Field AK . Oligonucleotides as inhibitors of human immunodeficiency virus.Curr. Opin. Mol. Ther.1(3), 323–331 (1999).
   PubMedGoogle Scholar
• Goldgur Y , CraigieR, CohenGHet al. Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design. Proc. Natl Acad. Sci. 96(23), 13040–13043 (1999).
   PubMed Web of Science ®Google Scholar
• Neamati N . Patented small molecule inhibitors of HIV-1 integrase: a 10-year saga.Expert Opin. Therap. Patents12(5), 709–724 (2002).
   Web of Science ®Google Scholar
• Billich A . S-1360 Shionogi-GlaxoSmithKline.Curr. Opin. Investig. Drugs4, 206–209 (2003).
   PubMedGoogle Scholar
• Grobler JA , StillmockK, HuBet al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc. Natl Acad. Sci. 99(10), 6661–6666 (2002).
   PubMed Web of Science ®Google Scholar
• Summa V , PetrocchiA, BonelliFet al. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem. 51(18), 5843–5855 (2008).
   PubMed Web of Science ®Google Scholar
• Al-Mawsawi LQ , Al-SafiRI, NeamatiN. Anti-infectives: clinical progress of HIV-1 integrase inhibitors.Expert Opin. Emerg. Drugs13(2), 213–225 (2008).
   PubMed Web of Science ®Google Scholar
• Palmisano L . Role of integrase inhibitors in the treatment of HIV disease.Expert Rev. Anti. Infect. Ther.5(1), 67–75 (2007).
   PubMed Web of Science ®Google Scholar
• Pommier Y , NeamatiN. Inhibitors of human immunodeficiency virus integrase.Adv. Virus Res.52, 427–458 (1999).
   PubMed Web of Science ®Google Scholar
• Young SD . Inhibition of HIV-1 integrase by small molecules: the potential for a new class of AIDS chemotherapeutics.Curr. Opin. Drug Discov. Devel.4(4), 402–410 (2001).
   PubMedGoogle Scholar
• Neamati N , MarchandC, PommierY. HIV-1 integrase inhibitors: past, present, and future.Adv. Pharmacol.49, 147–165 (2000).
   PubMedGoogle Scholar
• Gupta SP , NagappaAN. Design and development of integrase inhibitors as anti-HIV agents.Curr. Med. Chem.10(18), 1779–1794 (2003).
   PubMed Web of Science ®Google Scholar
• Witvrouw M , Van MaeleB, VercammenJet al. Novel inhibitors of HIV-1 integration. Curr. Drug Metab.5(4), 291–304 (2004).
   PubMed Web of Science ®Google Scholar
• Johns BA , SvoltoAC. Advances in two-metal chelation inhibitors of HIV integrase.Expert Opin. Therap. Patents18(11), 1225–1237 (2008).
   Web of Science ®Google Scholar
• Barreca ML , FerroS, RaoAet al. Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors. J. Med. Chem. 48(22), 7084–7088 (2005).
   PubMed Web of Science ®Google Scholar
• Kawasuji T , YoshinagaT, SatoAet al. A platform for designing HIV integrase inhibitors. Part 1: 2-hydroxy-3-heteroaryl acrylic acid derivatives as novel HIV integrase inhibitor and modeling of hydrophilic and hydrophobic pharmacophores. Bioorg. Med. Chem. 14(24), 8430–8445 (2006).
   PubMed Web of Science ®Google Scholar
• Deng J , DayamR, Al-MawsawiLQ, NeamatiN. Design of second generation HIV-1 integrase inhibitors.Curr. Pharm. Des.13(2), 129–141 (2007).
   PubMed Web of Science ®Google Scholar
• Pace P , Di FrancescoME, GardelliCet al. Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors. J. Med. Chem.50(9), 2225–2239 (2007).
   PubMed Web of Science ®Google Scholar
• Kirschberg T , ParrishJ. Metal chelators as antiviral agents.Curr. Opin. Drug Discov. Devel.10(4), 460–472 (2007).
   PubMedGoogle Scholar
• Wai JS , EgbertsonMS, PayneLSet al. 4-aryl-2,4-dioxobutanoic acid inhibitors of HIV-1 integrase and viral replication in cells. J. Med. Chem. 43(26), 4923–4926 (2000).
   PubMed Web of Science ®Google Scholar
• Walker MA , JohnsonT, NaiduBNet al. Benzyl amide-ketoacid inhibitors of HIV-integrase. Bioorg. Med. Chem. Lett. 17(17), 4886–4890 (2007).
   PubMed Web of Science ®Google Scholar
• Di Santo R , CostiR, RouxAet al. Novel bifunctional quinolonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, biological activities, and mechanism of action. J. Med. Chem. 49(6), 1939–1945 (2006).
   PubMed Web of Science ®Google Scholar
• Pais GC , ZhangX, MarchandCet al. Structure activity of 3-aryl-1,3-diketo-containing compounds as HIV-1 integrase inhibitors. J. Med. Chem. 45(15), 3184–3194 (2002).
   PubMed Web of Science ®Google Scholar
• Pais GCG , BurkeTR Jr. Novel aryl diketo-containing inhibitors of HIV–1 integrase. Drugs Future27(11), 1101–1111 (2002).
   Web of Science ®Google Scholar
• Kawasuji T , FujiM, YoshinagaT, SatoAet al. A platform for designing HIV integrase inhibitors. Part 2: a two-metal binding model as a potential mechanism of HIV integrase inhibitors. Bioorg. Med. Chem. 14(24), 8420–8429 (2006).
   PubMed Web of Science ®Google Scholar
• Zhuang L , WaiJS, EmbreyMWet al. Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J. Med. Chem. 46(4), 453–456 (2003).
   PubMed Web of Science ®Google Scholar
• Guare JP , WaiJS, GomezRPet al. A series of 5-aminosubstituted 4-fluorobenzyl-8-hydroxy-[1,6]naphthyridine-7-carboxamide HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 16(11), 2900–2904 (2006).
   PubMed Web of Science ®Google Scholar
• Hazuda DJ , YoungSD, GuareJPet al. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science 305(5683), 528–532 (2004).
   PubMed Web of Science ®Google Scholar
• Hazuda DJ , AnthonyNJ, GomezRPet al. A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc. Natl Acad. Sci. 101(31), 11233–11238 (2004).
   PubMed Web of Science ®Google Scholar
• Mousnier A , LehH, MouscadetJF, DargemontC. Nuclear import of HIV-1 integrase is inhibited in vitro by styrylquinoline derivatives. Mol. Pharmacol.66(4), 783–788 (2004).
   PubMed Web of Science ®Google Scholar
• Zouhiri F , MouscadetJF, MekouarKet al. Structure-activity relationships and binding mode of styrylquinolines as potent inhibitors of HIV-1 integrase and replication of HIV-1 in cell culture. J. Med. Chem. 43(8), 1533–1540 (2000).
   PubMed Web of Science ®Google Scholar
• Garvey EP , JohnsBA, GartlandMJet al. The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral. Antimicrob. Agents Chemother. 52(3), 901–908 (2008).
   PubMed Web of Science ®Google Scholar
• Johns BA , WeatherheadJG, AllenSHet al. The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: establishing the pharmacophore. Bioorg. Med. Chem. Lett. 19(6), 1802–1806 (2009).
   PubMed Web of Science ®Google Scholar
• Johns BA , WeatherheadJG, AllenSHet al. 1,3,4-oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position. Bioorg. Med. Chem. Lett. 19(6), 1807–1810 (2009).
   PubMed Web of Science ®Google Scholar
• Metobo SE , JinH, TsiangM, KimCU. Design, synthesis, and biological evaluation of novel tricyclic HIV-1 integrase inhibitors by modification of its pyridine ring.Bioorg. Med. Chem. Lett.16(15), 3985–3988 (2006).
   PubMed Web of Science ®Google Scholar
• Jones GS , YuF, ZeynalzadeganAet al. Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase. Antimicrob. Agents Chemother. 53(3), 1194–1203 (2009).
   PubMed Web of Science ®Google Scholar
• Summa V , PetrocchiA, MatassaVGet al. 4,5-dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species. J. Med. Chem. 49(23), 6646–6649 (2006).
   PubMed Web of Science ®Google Scholar
• Petrocchi A , KochU, MatassaVGet al. From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety. Bioorg. Med. Chem. Lett. 17(2), 350–353 (2007).
   PubMed Web of Science ®Google Scholar
• Vandeckerckhove L . GSK-1349572, a novel integrase inhibitor for the treatment of HIV infection.Curr. Opin. Investig. Drugs11(2), 203–212 (2010).
   PubMedGoogle Scholar
• Pace P , SpieserSA, SummaV. 4-hydroxy-5-pyrrolinone-3-carboxamide HIV-1 integrase inhibitors.Bioorg. Med. Chem. Lett.18(14), 3865–3869 (2008).
   PubMed Web of Science ®Google Scholar
• Kawasuji T , FujiM, YoshinagaTet al. 3-hydroxy-1,5-dihydro-pyrrol-2-one derivatives as advanced inhibitors of HIV integrase. Bioorg. Med. Chem. 15(16), 5487–5492 (2007).
   PubMed Web of Science ®Google Scholar
• Fisher TE , KimB, StaasDDet al. 8-hydroxy-3,4-dihydropyrrolo[1,2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 17(23), 6511–6515 (2007).
   PubMed Web of Science ®Google Scholar
• Langford HM , WilliamsPD, HomnickCFet al. Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 18(2), 721–725 (2008).
   PubMed Web of Science ®Google Scholar
• Wiscount CM , WilliamsPD, TranLOet al. 10-hydroxy-7,8-dihydropyrazino[1´,2´:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6 H)-diones: potent, orally bioavailable HIV-1 integrase strand-transfer inhibitors with activity against integrase mutants. Bioorg. Med. Chem. Lett. 18(16), 4581–4583 (2008).
   PubMed Web of Science ®Google Scholar
• Sato M , MotomuraT, AramakiHet al. Novel HIV-1 integrase inhibitors derived from quinolone antibiotics. J. Med. Chem. 49(5), 1506–1508 (2006).
   PubMed Web of Science ®Google Scholar
• Wai JS , KimB, FisherTEet al. Dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 17(20), 5595–5599 (2007).
   PubMed Web of Science ®Google Scholar
• Pace P , RowleyM. Integrase inhibitors for the treatment of HIV infection.Curr. Opin. Drug Discov. Devel.11(4), 471–479 (2008).
   PubMedGoogle Scholar
• Iwamoto M , WenningLA, PetryASet al. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin. Pharmacol. Ther. 83(2), 293–299 (2008).
   PubMed Web of Science ®Google Scholar
• Markowitz M , NguyenBY, GotuzzoEet 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. 46(2), 125–133 (2007).
   PubMed Web of Science ®Google Scholar
• Yazdanpanah Y , FagardC, DescampsDet al. High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial. Clin. Infect. Dis. 49(9), 1441–1449 (2009).
   PubMed Web of Science ®Google Scholar
• Thuret I , ChaixML, TamaletCet al. Aumaitre H, Blanche S. Raltegravir, etravirine and r-darunavir combination in adolescents with multidrug-resistant virus. AIDS 23(17), 2364–2366 (2009).
   PubMed Web of Science ®Google Scholar
• McKinnell JA , LinHY, NevinCNet al. Early virologic suppression with three-class experienced patients: 24-week effectiveness in the darunavir outcomes study. AIDS 23(12), 1539–1546 (2009).
   PubMed Web of Science ®Google Scholar
• Imaz A , del SazSV, RibasMAet al. Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection. J. Acquir. Immune Defic. Syndr.52(3), 382–386 (2009).
   PubMed Web of Science ®Google Scholar
• Towner W , KleinD, KerriganHLet al. Virologic outcomes of changing enfuvirtide to raltegravir in HIV-1 patients well controlled on an enfuvirtide based regimen: 24-week results of the CHEER study. J. Acquir. Immune Defic. Syndr. 51(4), 367–373 (2009).
   PubMed Web of Science ®Google Scholar
• De Castro N , BraunJ, CharreauI, PialouxGet al. Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1-infected patients: a randomized open-label trial. Clin. Infect. Dis. 49(8), 1259–1267 (2009).
   PubMed Web of Science ®Google Scholar
• Grant PM , PalmerS, BendavidEet al. Switch from enfuvirtide to raltegravir in virologically suppressed HIV-1 infected patients: effects on level of residual viremia and quality of life. J. Clin. Virol. 46(4), 305–308 (2009).
   PubMed Web of Science ®Google Scholar
• Lennox JL , DeJesusE, LazzarinAet 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. 374(9692), 796–806 (2009).
   PubMed Web of Science ®Google Scholar
• De Clercq E . A new drug combination therapy for treatment-naive patients with HIV-1 infection, consisting of raltegravir, emtricitabine and tenofovir disoproxil fumarate.Expert Opin. Pharmacother.10(17), 2935–2937 (2009).
   PubMed Web of Science ®Google Scholar
• McColl DJ , ChenX. Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy.Antiviral Res.85(1), 101–118 (2009).
   PubMed Web of Science ®Google Scholar
• Kobayashi M , NakaharaK, SekiTet al. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res. 80(2), 213–222 (2008).
   PubMed Web of Science ®Google Scholar
• Shimura K , KodamaE, SakagamiYet al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J. Virol. 82(2), 764–774 (2008).
   PubMed Web of Science ®Google Scholar
• Marinello J , MarchandC, MottBTet al. Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Biochemistry 47(36), 9345–9354 (2008).
   PubMed Web of Science ®Google Scholar
• Ramanathan S , ShenG, HinkleJet al. Pharmacokinetics of coadmistered ritonavir-boosted elvitegravir and zidovirine, didanosine, stavudine or abacavir. J. Acquir. Immune Defic. Syndr. 46(2), 160–166 (2007).
   PubMedGoogle Scholar
• Buzon MJ , DalmauJ, PuertasMCet al. The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates. AIDS 24(1), 17–25 (2009).
   Web of Science ®Google Scholar
• Fransen S , KarmochkineM, HuangWet al. Longitudinal analysis of raltegravir susceptibility and integrase replication capacity of human immunodeficiency virus type 1 during virologic failure. Antimicrob. Agents Chemother. 53(10), 4522–4524 (2009).
   PubMed Web of Science ®Google Scholar
• Delelis O , MaletI, NaLet al. The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Nucleic Acids Res. 37(4), 1193–1201 (2009).
   PubMed Web of Science ®Google Scholar
• Malet I , DelelisO, ValantinMAet al. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob. Agents Chemother. 52(4), 1351–1358 (2008).
   PubMed Web of Science ®Google Scholar
• Delelis O , ThierryS, SubraFet al. Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo. Antimicrob. Agents Chemother. 54(1), 491–501 (2009).
   PubMed Web of Science ®Google Scholar
• Sichtig N , SierraS, KaiserRet al. Evolution of raltegravir resistance during therapy. J. Antimicrob. Chemother. 64(1), 25–32 (2009).
   PubMed Web of Science ®Google Scholar
• Malet I , DelelisO, SoulieCet al. Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. J. Antimicrob. Chemother. 63(4), 795–804 (2009).
   PubMed Web of Science ®Google Scholar
• Sitzmann M , FilippovIV, NicklausMC. Internet resources integrating many small-molecule databases.SAR QSAR Environ. Res.19(1–2), 1–9 (2008).
   PubMed Web of Science ®Google Scholar

Websites

• National AIDS treatment advocacy project www.natap.org/2008/ICAAC/ICAAC_68.htm
   Google Scholar
• Clinicaltrials.gov http://clinicaltrials.gov/ct2/show/NCT00869557
   Google Scholar