Clinical Use of Raltegravir: A Review

• Lewden C , CheneG, MorlatPet al.: HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population.J. Acquir. Immune Defic. Syndr.46(1), 72–77(2007).
   PubMed Web of Science ®Google Scholar
• van Sighem A , GrasL, ReissP, BrinkmanK, de WolfF, ATHENA National Observational Cohort Study: Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA 16–19 February (2010) (Abstract 526).
   Google 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. USA96(23), 13040–13043(1999).
   PubMed Web of Science ®Google Scholar
• Hazuda D , BlauCU, FelockPet al.: Isolation and characterization of novel human immunodeficiency virus integrase inhibitors from fungal metabolites.Antivir. Chem. Chemother.10(2), 63–70(1999).
   PubMed Web of Science ®Google Scholar
• Miller M , BarnardR, WitmerMet al.: Short-term RAL monotherapy does not predispose patients to develop RAL resistance during subsequent combination therapy: analysis of samples from Protocol 004. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 557).
   Google Scholar
• Damond F , LarivenS, RoquebertBet al.: Virological and immunological response to HAART regimen containing integrase inhibitors in HIV-2-infected patients.AIDS22(5), 665–666(2008).
   PubMed Web of Science ®Google Scholar
• Briz V , GarridoC, PovedaEet al.: Raltegravir and etravirine are active against HIV type 1 group O.AIDS Res. Hum. Retroviruses25(2), 225–227(2009).
   PubMed Web of Science ®Google Scholar
• Kassahun K , McIntoshI, CuiDet al.: Absorption, metabolism and excretion of MK-0518, a potent HIV-1 integrase inhibitor, in healthy male volunteers. Program and abstracts of the 46th ICAAC. San Francisco, CA, USA, 27–30 September (2006) (Abstract A-0372).
   Google Scholar
• Markowitz M , Morales-RamirezJO, NguyenBYet 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.43(5), 509–515(2006).
   PubMed Web of Science ®Google Scholar
• Wenning LA , HwangE, Nguyen B-Y et al.: Pharmacokinetic/pharmacodynamic analyses for raltegravir in Phase III studies in treatment-experienced HIV-infected patients following 48 weeks of treatment. Program and abstracts of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC, USA, 25–28 October (2008) (Abstract H-4054).
   Google Scholar
• Grobler JA , McKennaPM, LySet al.: Functionally irreversible inhibition of integration by slowly dissociating strand transfer inhibitors. Program and abstracts of the 10th International Workshop on Clinical Pharmacology of HIV Therapy. Amsterdan, Holland, 15–17 April (2009) (Abstract O-10).
   Google Scholar
• Bonora S , D‘AvolioA, SimieleMet al.: Steady-state raltegravir penetration in seminal plasma of healthy volunteers. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 6–19 February (2010) (Abstract 609).
   Google Scholar
• Clavel C , MandelbrotL, Marcelin A-G et al.: Raltegravir concentrations in the cervicovaginal compartment exceed the median inhibitory concentration in HIV-1-infected women treated with a raltegravir-containing regimen: DIVA 01 Study. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 608).
   Google Scholar
• Yilmaz A , GisslénM, SpudichSet al.: Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.PLoS One4(9), e6877 (2009).
   PubMed Web of Science ®Google Scholar
• Luber A , SlowinskiPD, AcostaEet al.: Steady-state pharmacokinetics of fosamprenavir and raltegravir alone and combined with unboosted and ritonavir-boosted fosamprenavir. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA, USA, 12–15 September (2009) (Abstract A1-1297).
   Google Scholar
• Gupta S , LatailladeM, FarberS, KozalMJ: Raltegravir with unboosted atazanavir 300 mg twice daily in antiretroviral treatment-experienced participants.J. Int. Assoc. Physicians AIDS Care8, 87–92(2009).
   Google Scholar
• Ripamonti D , MaggioloF, BombanaEet al.: Efficacy, safety and tolerability of dual therapy with raltegravir and atazanavir in antiretroviral experienced patients. Program and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa, 19–22 July (2009) (Abstract MOPEB067).
   Google Scholar
• Ruane PJ , AlasB: Dual maintenance therapy with raltegravir bid with atazanavir qd in patients with no prior pi resistance and intolerance to other ARV regimens: preliminary report. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA, USA, 12–15 September (2009) (Abstract H-914).
   Google Scholar
• Cattaneo D , RipamontiD, BaldelliS, CozziV, ContiF, ClementiE: Exposure-related effects of unboosted atazanavir on the pharmacokinetics of raltegravir in HIV-1 infected patients. Program and abstracts of the 11th International Workshop on Clinical Pharmacology and HIV Therapy. Sorrento, Italy, 7–9 April (2010) (Abstract 49).
   Google Scholar
• Giguere P , la PorteC, ZhangG, CameronB: Pharmacokinetics of darunavir, etravirine and raltegravir in an HIV-infected patient on haemodialysis. AIDS23(6), 740–742(2009).
   PubMed Web of Science ®Google Scholar
• Iwamoto M , KassahunK, TroyerMDet al.: Lack of a pharmacokinetic effect of raltegravir on midazolam: in vitro/in vivo correlation.J. Clin. Pharmacol.48(2), 209–214(2008).
   PubMed Web of Science ®Google Scholar
• ISENTRESS Package insert. Merck, USA (2010).
   Google Scholar
• Baldanti F , PaolucciS, GulminettiR, BrandoliniM, BarbariniG, MaseratiR: Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens.J. Med. Virol.82(1), 116–122(2010).
   PubMed Web of Science ®Google Scholar
• da Silva D , Van WesenbeeckL, BreilhDet al.: HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens. J. Antimicrob. Chemother.65(6), 1262–1269(2010).
   PubMed Web of Science ®Google Scholar
• Roquebert B , MatheronS, BenardAet al.: Raltegravir genetic resistance patterns in HIV-2 infected patients failing raltegravir-containing regimen. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 558).
   Google Scholar
• Hatano H , LampirisH, FransenSet al.: Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy.J. Acquir. Immune Defic. Syndr.54(4), 389–393(2010).
   PubMed Web of Science ®Google Scholar
• Nakahara K , Wakasa-MorimotoC, KobayashiMet al.: Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics.Antiviral Res.81(2), 141–146(2009).
   PubMed Web of Science ®Google Scholar
• Miller M , DanovichY, WitmerMet al.: Longitudinal analysis of resistance to the HIV-1 integrase inhibitor raltegravir: results from P005 a Phase II study in treatment experienced patients.Antiviral Ther.13, A8 (2008).
   Web of Science ®Google Scholar
• van Baelen K , Van EygenV, RondelezE, StuyverLJ: Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility. AIDS22(14), 1877–1880(2008).
   PubMed Web of Science ®Google Scholar
• Low A , PradaN, TopperMet al.: Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors.Antimicrob. Agents Chemother.53(10), 4275–4282(2009).
   PubMed Web of Science ®Google Scholar
• Ceccherini-Silberstein F , ArmeniaD, D‘ArrigoRet al.: Primary mutations associated with resistance to raltegravir are not detectable by pyrosequencing in integrase inhibitors-naive patients. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 566).
   Google Scholar
• Passaes CB , GuimaraesML, FernandezSLet al.: Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil.J. Acquir. Immune Defic. Syndr.51(1), 7–12(2009).
   PubMed Web of Science ®Google Scholar
• Armenia D , FabeniL, MaletIet al.: Impact of baseline HIV-1 polymorphisms with virological outcome in patients starting a raltegravir-containing regimen. Presented at: The 8th European HIV Drug Resistance Workshop, From Basic Science to Clinical Decision Making 2010. Sorrento, Italy, 17–19 March, 2010.
   Google Scholar
• Wirden M , SimonA, SchneiderLet al.: Raltegravir has no residual antiviral activity in vivo against HIV-1 with resistance-associated mutations to this drug.J. Antimicrob. Chemother.64(5), 1087–1090(2009).
   PubMed Web of Science ®Google Scholar
• Grinsztejn B , NguyenBY, KatlamaCet al.: 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.Lancet369(9569), 1261–1269(2007).
   PubMed Web of Science ®Google Scholar
• Steigbigel RT , CooperDA, TepplerHet al.: Long-term efficacy and safety of raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials.Clin. Infect. Dis.50(4), 605–612(2009).
   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.Lancet374(9692), 796–806(2009).
   PubMed Web of Science ®Google Scholar
• DeJesus E , CohenC, LennoxJet al.: Metabolic profiles and body composition changes in treatment-naive HIV-infected patients treated with raltegravir 400 mg twice-daily vs efavirenz 600 mg each bedtime combination therapy: 96-week follow-up. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 720).
   Google Scholar
• Markowitz M , NguyenBY, GotuzzoEet al.: Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection.J. Acquir. Immune Defic. Syndr.52(3), 350–356(2009).
   PubMed Web of Science ®Google Scholar
• Lennox JL , DejesusE, BergerDSet al.: Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses.J. Acquir. Immune Defic. Syndr.55(1), 39–48(2010).
   PubMed Web of Science ®Google Scholar
• Harris M , LarsenG, MontanerJS: Exacerbation of depression associated with starting raltegravir: a report of four cases.AIDS22(14), 1890–1892(2008).
   PubMed Web of Science ®Google Scholar
• Zembower TR , GerzenshteinL, ColemanK, PalellaFJ: Severe rhabdomyolysis associated with raltegravir use.AIDS22(11), 1382–1384(2008).
   PubMed Web of Science ®Google Scholar
• Tsukada K , TeruyaK, TasatoD, GatanagaH, KikuchiY, OkaS: Raltegravir-associated perihepatitis and peritonitis: a single case report.AIDS24(1), 160–161(2010).
   PubMed Web of Science ®Google Scholar
• Rockstroh J , TepplerH, ZhaoJet al.: Hepatic safety and efficacy of raltegravir in patients co-infected with HIV and HBV or HCV. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract MOPEB067).
   Google Scholar
• Spivak A , RezaA, McMahonM, SedaghatA, SilicianoR: Understanding decay of viremia in patients on raltegravir. Program and abstracts of the 16th Conference on Retrovirus and Opportunistic Infections. Montreal, Canada, 8–11 February (2009) (Abstract P552).
   Google Scholar
• Gottuzo E , Nguyen B-Y, Markowitz M et al.: Sustained antiretroviral efficacy of raltegravir after 192 weeks of combination ART in treatment-naive HIV-1-infected patients. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 514).
   Google Scholar
• Steigbigel RT , CooperDA, KumarPNet al.: Raltegravir with optimized background therapy for resistant HIV-1 infection.N. Engl. J. Med.359(4), 339–354(2008).
   PubMed Web of Science ®Google Scholar
• Eron JJ , CooperD, SteigbigelRet al.: Sustained antiretroviral effect of raltegravir at week 156 in the BENCHMRK Studies and exploratory analysis of late outcomes based on early virologic responses. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 515).
   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
• Roquebert B , ColinC, Taburet A-M et al.: Bulk and clonal resistance analyses in highly experienced patients failing raltegravir-, etravirine-, and darunavir/ritonavir-containing regimen (ANRS 139 TRIO Trial). Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 593).
   Google Scholar
• Nozza S , GalliL, ViscoFet al.: Raltegravir, maraviroc, etravirine: an effective protease inhibitor and nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in HIV-infected patients with triple-class experience.AIDS24(6), 924–928(2010).
   PubMed Web of Science ®Google Scholar
• de Castro N , BraunJ, CharreauIet 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
• Talbot A , MachoufN, ThomasRet al.: Switch from enfuvirtide to raltegravir in patients with undetectable viral load: efficacy and safety at 24 weeks in a Montreal cohort.J. Acquir. Immune Defic. Syndr.51(3), 362–364(2009).
   PubMed Web of Science ®Google Scholar
• Santos JR , LibreJM, FerrerEet al.: Efficacy and safety of switching from enfuvirtide to raltegravir in patients with virological suppression.HIV Clin. Trials10(6), 432–438(2009).
   PubMed Web of Science ®Google Scholar
• Eron JJ , YoungB, CooperDAet al.: Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials.Lancet375(9712), 396–407(2010).
   PubMed Web of Science ®Google Scholar
• Martinez E , LarrousseM, LibreJMet al.: Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study.AIDS24(11), 1697–1707(2010).
   PubMed Web of Science ®Google Scholar
• Mira L , Lopez-CortesL, BarreiroPet al.: Efficacy of pegylated interferon + ribavirin treatment in HIV/HCV-co-infected patients receiving abacavir + lamivudine or tenofovir + either lamivudine or emtricitabine as nucleoside analogue backbone. Program and abstracts of the 15th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA (2010) (Abstract 1074).
   Google Scholar
• Butt AA : Fatal lactic acidosis and pancreatitis associated with ribavirin and didanosine therapy.AIDS Read.13(7), 344–348(2003).
   PubMedGoogle Scholar
• Alvarez D , DieterichDT, BrauN, MooreheadL, BallL, SulkowskiMS: Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons.J. Viral Hepat.13(10), 683–689(2006).
   PubMed Web of Science ®Google Scholar
• Buzon MJ , MassanellaM, LlibreJet al.: HIV-1 replication and immune dynamics are impacted by raltegravir intensification of HAART-suppressed patients. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 100LB).
   Google Scholar
• de Laugerre C , CharreauI, BraunJet al.: No evolution of HIV-1 total DNA and 2-LTR circles after 48 weeks of raltegravir-containing therapy in patients with controlled viremia: a sub-study of the randomized EASIER-ANRS 138 Trial. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 281).
   Google Scholar
• Hatano H , HayesT, DahlVet al.: Raltegravir intensification in antiretroviral-treated patients exhibiting a suboptimal CD4+ T cell response. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 101LB).
   Google Scholar
• Karim ASS , NaidooK, GroblerAet al.: Timing of initiation of antiretroviral drugs during tuberculosis therapy.N. Engl. J. Med.362(8), 697–706(2010).
   PubMed Web of Science ®Google Scholar
• Patel A , PatelK, PatelJ, ShahN, PatelB, RaniS: Safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naive patients in India who are coinfected with tuberculosis and HIV-1.J. Acquir. Immune Defic. Syndr.37(1), 1166–1169(2004).
   PubMed Web of Science ®Google Scholar
• Friedland G , KhooS, JackC, LallooU: Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV.J. Antimicrob. Chemother.58(6), 1299–1302(2006).
   PubMed Web of Science ®Google Scholar
• Schmitt C , RiekM, WintersK, SchutzM, GrangeS: Unexpected hepatotoxicity of rifampin and saquinavir/ritonavir in healthy male volunteers.Arch. Drug Inf.2(1), 8–16(2009).
   PubMedGoogle Scholar
• La Porte CJ , ColbersEP, BertzRet al.: Pharmacokinetics of adjusted-dose lopinavir–ritonavir combined with rifampin in healthy volunteers.Antimicrob. Agents Chemother.48(5), 1553–1560(2004).
   PubMed Web of Science ®Google Scholar
• Miller M , DanovichR, FransenSet al.: Analysis of resistance to the HIV-1 integrase inhibitor raltegravir: results from the Benchmrk 1 and 2. Program and abstracts of the 48th ICAAC. Washington DC, USA (2008) (Abstract 898).
   Google Scholar
• Canducci F , MarinozziMC, SampaoloMet al.: Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir.J. Antimicrob. Chemother.65(3), 425–433(2010).
   PubMed Web of Science ®Google Scholar
• Seki T , KobayashiM, Wakasa-MorimotoCet al.: S/GSK1349572 is a potent next generation hiv integrase inhibitor and demonstrates a superior resistance profile substantiated with 60 integrase mutant molecular clones. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 554).
   Google Scholar
• Marcelin A -G, Malet I, Fabeni L et al.: Resistance-associated mutations to integrase inhibitor S/GSK1349572 in HIV-1 integrase inhibitor-naive and raltegravir-experienced patients. Program and abstracts of the 17th Conference on Retrovirus and Opportunistic Infections. San Francisco, CA, USA, 16–19 February (2010) (Abstract 554).
   Google Scholar
• Gatell JM , KatlamaC, GrinsztejnBet al.: Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study.J. Acquir. Immune Defic. Syndr.53(4), 456–463(2010).
   PubMed Web of Science ®Google Scholar

Websites

• DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, December 1 (2009) http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
   Google Scholar
• European AIDS Clinical Society (EACS) Guidelines: Clinical Management and Treatment of HIV Infected Adults in Europe, version 5 (2009) http://www.europeanaidsclinicalsociety.org/guidelinespdf/1_Treatment_of_HIV_Infected_Adults.pdf
   Google Scholar