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Expert Opinion on Pharmacotherapy Volume 10, 2009 - Issue 15
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Reviews

New antiretroviral drugs: a review of the efficacy, safety, pharmacokinetics, and resistance profile of tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir

Christine A Hughes Associate Professor and Clinical Pharmacotherapy Practitioner, HIV, Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Northern Alberta HIV Program, Edmonton, AB T6G 2N8, Canada
, BScPharm PharmD FCSHP,
Linda Robinson HIV Clinical Pharmacy Specialist, Windsor Regional Hospital, Windsor, ON N8W 1E3, Canada
, BScPharm AAHIVE,
Alice Tseng HIV Pharmacotherapy Specialist, Assistant Professor, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto General Hospital, Toronto, ON M5G 2N2, Canada
, BScPharm PharmD FCSHP &
Rodger D MacArthur Professor of Medicine, Wayne State University, Division of Infectious Diseases, Detroit, Michigan 48201, USA +1 313 993 0921; +1 313 745 3638; [email protected]
, MD
Pages 2445-2466 | Published online: 13 Aug 2009

Bibliography

  • Walmsley S, Bernstein B, King M, et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002;346:2039-46
  • Noor MA, Parker RA, O'Mara E, et al. The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. AIDS 2004;18:2137-44
  • Walmsley S, Avihingsanon A, Slim J, et al. Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults. J Acquir Immune Defic Syndr 2009;50:367-74
  • Eron J Jr, Yeni P, Gathe J Jr, et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir ritonavir in combination with abacavir-lamivudine for initial treatment of HIV infection over 48 weeks: a randomized non-inferiority trial. Lancet 2006;368:476-82
  • Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naïve HIV-1 infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet 2008;372:646-55
  • Oritz R, Dejesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naïve HIV-1-infected patients at week 48. AIDS 2008;22:1389-97
  • Orman JS, Perry CM. Tipranavir. A review of its use in the management of HIV infection. Drugs 2008;68:1435-63
  • Sabo J, Elgadi M, Wruck J, et al. The pharmacokinetic interaction between atazanavir/ritonavir and steady-state tipranavir/ritonavir in healthy volunteers [abstract 41]. 7th International Workshop on Clinical Pharmacology of HIV Therapy, Lisbon. April 20-22, 2006
  • Leith J, Walmsley S, Katlama C, et al. Pharmacokinetics and safety of tipranavir/ritonavir alone or in combination with saquinavir, amprenavir, or lopinavir: interim analysis of BI1182.51 [abstract]. 5th International Workshop on Clinical Pharmacology of HIV Therapy, Rome, Italy. April 1-3, 2004
  • Peytavin G, Marcelin AG, Rouault A, et al. Therapeutic drug monitoring of boosted tipranavir with and without combination to lopinavir or fosamprenavir [abstract 591]. 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO. February 5-8, 2006
  • Harris M, Ramirez S, Joy R, et al. Effect of lopinavir and ritonavir dose adjustments on the pharmacokinetic interaction between LPV/RTV and tipranavir [abstract 584]. 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO. February 5-8, 2006
  • Roszko PJ, Curry K, Brazina B, et al. Standard doses of efavirenz, zidovudine, tenofovir, and didanosine may be given with tipranavir/ritonavir [abstract 865]. 2nd IAS Conference on HIV and Pathogenesis, Paris, France. July 14-17, 2003
  • La Porte CJL, Sabo J, Beique LC, et al. Lack of effect of efavirenz 600 mg QD on the pharmacokinetics of tipranavir/ritonavir 500/200 mg BID in healthy volunteers [abstract A-1421]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. September 17-20, 2007
  • Sabo J, MacGregor T, Lamson M, et al. Pharmacokinetics of tipranavir and nevirapine [abstract 249]. 10th Annual Canadian Conference on HIV/AIDS Research, Toronto. May 31-June 3, 2001
  • Tibotec, Inc. Intelence® (etravirine) product monograph. USA: January 2008
  • Scholler M, Kraft M, Hoetelmans RM, et al. Significant decrease in TMC125 exposures when co-administered with tipranavir boosted with ritonavir in healthy subjects [abstract 583]. 13th Conference on Retroviruses and Opportunistic Infections Denver, CO. February 5-8, 2006
  • Abel S, Taylor-Worth R, Ridgeway C, et al. Effect of boosted tipranavir on the pharmacokinetics of maraviroc (UK 427,857) in healthy volunteers [abstract LBPE4.3/15]. 10th European AIDS Conference, Dublin. November 17-20, 2005
  • Mathias A, Hinkle J, Enejosa J, et al. Lack of pharmacokinetic interaction between ritonavir-boosted GS-9137 (elvitegravir) and tipranavir/ritonavir [abstract TUPDB06]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia. July 22-25, 2007
  • Wenning LA, Hanley H, Stone J, et al. Effect of tipranavir + ritonavir on pharmacokinetics of MK-0518 [abstract A-0374]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA. September 27-30, 2006
  • Boehringer Ingelheim Pharmaceuticals, Inc. Aptivus® (tipranavir) product monograph. USA: June 2008
  • Tibotec, Inc. Prezista® (darunavir) product monograph. USA: February 2009
  • Hicks CB, Cahn P, Cooper DA, et al. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1 infected patients at 48 weeks in the Randomized Evaluation of Intervention in multi-drug resistant patients with Tipranavir (RESIST) studies: an alalysis of combined data from two randomized open-label trials. Lancet 2006;368:466-75
  • Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. November 3, 2008. Available from: http://aidsinfo.nih.gov/ contentfiles/AdultandAdolescentGL.pdf
  • Chrysos G, Gerakari S, Stasini F, et al. Intracranial hemorrhage possibly related to tipranavir in an HIV-1 patient with cryptococcal meningitis. J Infect 2008;57:85-7
  • Marcelin AG, Masquelier B, Desamps D, et al. Tipranavir-ritonavir genotypic resistance score in protease inhibitor-experienced patients. Antimicrob Agents Chemother 2008;52:3237-43
  • Fenton C, Perry CM. Darunavir in the treatment of HIV-1 infection. Drugs 2007;67:2791-801
  • Clotet B, Bellos N, Molina JM, et al. Efficacy and safetly of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet 2007;369(968):1169-78. Erratum in: Lancet 2008 Jan 12;371(9607):116
  • Molina JM, Cohen C, Katlama C, et al. Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24 week results of POWER 3. J Acquir Immune Defic Syndr 2007;46:24-31
  • Madruga JV, Berger D, McMurchie M, et al. Efficacy and safety of darunavir-ritonavir compated with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet 2007;370:49-58
  • Andries K, Azijn H, Thielemans T, et al. TMC125, a novel next-generation non-nucleoside reverse transcriptase inhibitor active against non-nucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2004;48:4680-6
  • deMeyer S, Vangeneugden T, van Baelen B, et al. Resistance profile of darunavir: combined 24-week results from the POWER trials. AIDS Res Hum Retroviruses 2008;24:379-88
  • Bristol-Myers Squibb Canada. Sustiva® (efavirenz) prescribing information. Montreal, QC: 2004
  • Boehringer Ingelheim (Canada) Ltd. Viramune® (nevirapine) product monograph. Burlington, ON: August 30, 2004
  • Hirsch MS, Günthard HF, Schapiro JM, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 2008;47:266-85
  • Wheeler W, Mahle K, Bodnar U, et al. Antiretroviral drug-resistance mutations and subtypes in drug-naive persons newly diagnosed with HIV-1 infection, US, March 2003 to October 2006 [abstract 648]. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA. February 25-28, 2007
  • Das K, Clark ADJ, Lewi PJ, et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 2004;47:2250-60
  • Scholler-Gyure M, Boffito M, Pozniak A, et al. Effects of different meal compositions and fasted state on the oral bioavailability of etravirine. Pharmacother 2008;28:1215-22
  • Scholler-Gyure M, Kakuda TN, De Smedt G, et al. Pharmacokinetics of TMC125 in QD and BID regimens in HIV-1 negative volunteers [abstract A-1427]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. September 17-20, 2007
  • Kakuda TN, Scholler-Gyure M, Peeters M, et al. Pharmacokinetics of etravirine are not affected by sex, age, race, use of enfuvirtide or treatment duration in HIV-1 infected patients [abstract P34]. 9th International Workshop on Clinical Pharmacology of HIV Therapy, New Orleans, LA. April 7-9, 2008
  • Scholler-Gyure M, Kakuda TN, De Smedt G, et al. Pharmacokinetics of TMC125 in HIV-1 negative volunteers with mild and moderate hepatic impairment [abstract A-1428]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. September 17-20, 2007
  • Raoof A, Lachau-Durand S, Verbeeck J, et al. Etravirine has no effect on fetal development in rats and rabbits [abstract TUPE0013]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Furco A, Gosrani B, Nicholas S, et al. Successful use of darunavir, etravirine, enfuvirtide and tenofovir/emtricitabine in pregnant woman with multiclass HIV resistance. AIDS 2009;23:434-5
  • Scholler-Gyure M, Kakuda TN, Stevens T, et al. Effect of etravirine on cytochrome P450 isozymes assessed by the Cooperstown 5+1 cocktail [abstract A-955]. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC. October 25-28, 2008
  • Ruxrungtham K, Pedro RJ, Latiff GH, et al. Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor-naïve, non-nucleoside reverse transcriptase inhibitor-experienced patients: study TMC125-C227. HIV Med 2008;9:883-96
  • Boffito M, Winston A, Jackson A, et al. Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. AIDS 2007;21:1449-55
  • Katlama C, Gatell JM, Molina JM, et al. Pooled 24-week results of DUET-1 and DUET-2: efficacy of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients [abstract P7.13/18]. 11th European AIDS Conference. Madrid, Spain: October 24-27, 2007
  • Madruga JV, Cahn P, Grinsztejn B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007;370:29-38
  • Lazzarin A, Campbell T, Clotet B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24 week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007;370:39-48
  • Trottier B, Johnson M, Katlama C, et al. Pooled 48-week analysis of DUET-1 and DUET-2: durable efficacy and safety results of etravirine (TMC125) in treatment-experienced HIV-infected patients [abstract P167]. 17th Annual Canadian Conference on HIV Research Montreal, QC. April 24-27, 2008
  • Cahn P, Molina JM, Towner W, et al. 48-week pooled analysis of DUET-1 and DUET-2: the impact of baseline characteristics on virologic response to etravirine [abstract TUPE0047]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Di Perri G, Madruga JV, Sathasivam K, et al. The impact of background regimen on virologic response to etravirine: pooled 48-week analysis to DUET-1 and DUET-2 [abstract TUPE0061]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Haubrich R, Eron J, Thompson M, et al. Reduction in AIDS-defining events/death with etravirine compared to placebo: pooled DUET 48-week results [abstract H-1239]. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC. October 25-28, 2008
  • Yazdanpanah Y, Fagard C, Descamps D, et al. High rate of virologic success with raltegravir plus etravirine and darunavir/ritonavir in treatment-experienced patients with multidrug resistant virus [abstract THAB0406]. 17th International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Kerrigan H, Towner W, Klein D, Follansbee S. Treatment response among HIV patients co-enrolled in the etravirine and raltegravir expanded access programs at Kaiser Permanente [abstract H-1263]. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC. October 25-28, 2008
  • Katlama C, Campbell T, Schechter M, et al. Incidence and severity of nervous system and psychiatric events are similar with etravirine versus placebo: pooled 48 week data from the Phase III DUET studies [abstract TUPE0056]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Haubrich R, Cahn P, Grinsztejn B, et al. DUET-1: week 48 results of a phase III randomized double-blind trial to evaluate the efficacy and safety of TMC125 vs placebo in 612 treatment-experienced HIV-1-infected patients [abstract 791]. 15th Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 3-6, 2008
  • Mills A, Grinsztejn B, Katlama C, et al. The incidence of rash observed with the NNRTI etravirine in the Phase III DUET trials using pooled 48-week data [abstract TUPE0059]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Madruga JV, Cahn P, Grinsztejn B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1 infected patients in DUET-1: 24-week results from a randomized, double-blind, placebo-controlled trial. Lancet 2007;370:29-38
  • Vingerhoets J, Peeters M, Azijn H, et al. An update of the list of NNRTI mutations associated with decreased virological response to etravirine: multivariate analyses on the pooled DUET-1 and DUET-2 clinical trial data. Antivir Ther 2008;13(Suppl 3):A26
  • MacArthur RD, Huppler Hullsiek K, Peng G, et al. Failing therapy with efavirenz results in significantly fewer mutations limiting to etravirine than failing therapy with nevirapine: on-treatment analyses from the CPCRA FIRST Study. Antivir Ther 2008;13(Suppl 3):A141
  • Verloes R, Van't Klooster G, Baert L, et al. TMC278 long acting – a parenteral nanosuspension formulation that provides sustained clinically relevant plasma concentrations in HIV-negative volunteers [abstract TUPE0042]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Van Gyseghem E, Pendela M, Baert L, et al. Power for reconstitution of the anti-HIV-1 drug TMC278 - formulation development, stability and animal studies. Eur J Pharm Biopharm 2008;70:853-60
  • De Bethune M, Andries K, Azijn H, et al. TMC-278, a new potent NNRTI, with an increased barrier to resistance and good pharmacokinetic profile [abstract 556]. 12th Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 22-25, 2005
  • Crauwels H, Van Heeswijk RP, Bollen A, et al. The effect of different types of food on the bioavailability of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) [abstract P32]. 9th International Workshop on Clinical Pharmacology of HIV Therapy, New Orleans, LA. April 7-9, 2008
  • Hoetelmans R, Van Heeswijk R, Kestens D, et al. Effect of food and multiple-dose pharmacokinetics of TMC278 as an oral tablet formulation [abstract TuPe3.1B10]. 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, Brazil. July 24-27, 2005
  • Van Heeswijk R, Hoetelmans R, Kestens D. The effects of TMC 278, a next generation non-nucleoside reverse transcriptase inhibitor, on the pharmacokinetics of acetaminophen and CYP2E1 activity in HIV-negative volunteers [abstract 67]. 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, Hungary. April 16-18, 2007
  • Van Heeswijk R, Hoetelmans R, Aharchi F, et al. The pharmacokinetic interaction between atorvastatin and TMC278, a next-generation non-nucleoside reverse transcriptase inhibitor in HIV-negative volunteers [P4.3/04]. 11th European AIDS Conference, Madrid, Spain. October 24-27, 2007
  • Hoetelmans RM, Kestens D, Stevens M, et al. Pharmacokinetic interaction between the novel non-nucleoside reverse transcriptase inhibitor TMC278 and tenofovir disoproxil fumarate in healthy volunteers [abstract 18]. 6th International Workshop on Clinical Pharmacology of HIV Therapy, Quebec city, QC. April 28-30, 2005
  • Van Heeswijk RP, Hoetelmans RM, Kestens D, et al. The pharmacokinetic (PK) interaction between famotidine and TMC278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), in HIV-negative volunteers [abstract TUPDB01]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia. July 22-25, 2007
  • Van Heeswijk R, Hoetelmans R, Kestens D, et al. The effects of CYP3A4 modulation on the pharmacokinetics of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor [abstract 74]. 7th International Workshop of Clinical Pharmacology of HIV Therapy, Lisbon, Portugal. April 20-22, 2007
  • Goebel F, Yakovlev A, Pozniak A, et al. TMC278: potent anti-HIV activity in antiretroviral therapy-naive patients [abstract 160]. 12th Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 22-25, 2005
  • Yeni P, Goebel F, Thompson M, et al. TMC278, a next-generation NNRTI demonstrates potent and sustained efficacy in antiretroviral-naive patients: week 48 primary analysis of study TMC278-C204 [abstract P7.2/07]. 11th European AIDS Conference, Madrid, Spain. October 24-27, 2007
  • Santoscoy M, Cahn P, Gonsalez C, et al. TMC278 (rilpivirine), a next-generation NNRTI, demonstrates long-term efficacy and tolerability in ARV-naive patients: 96 week results of study C204 [abstract TUAB0103]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Pozniak A, Steyn D, Grinsztejn B, et al. Less frequent reporting of central nervous system and psychiatric adverse events with TMC278 than with efavirenz [abstract WEPEA105]. 4th IAS Conference on HIV Pathogensis, Treatment and Prevention, Sydney, Australia. July 22-25, 2007
  • Pozniak A, Yazdanpanah Y, Shalit P, et al. Lower lipid levels in antiretroviral-naive patients receiving the investigational NNRTI TMC278 versus efavirenz [abstract P9.2/05]. 11th European AIDS Conference, Madrid, Spain. October 24-27, 2007
  • Briz V, Poveda E, Soriano V. HIV entry inhibitors: mechanisms of action and resistance pathways. J Antimicrob Chemother 2006;57:619-27
  • Este JA, Telenti A. HIV entry inhibitors. Lancet 2007;370:81-8
  • Weber J, Piontkivska H, Quinones-Mateu ME. HIV type 1 tropism and inhibitors of viral entry: clinical implications. AIDS Rev 2006;8:60-77
  • Paxton WA, Martin SR, Tse D, et al. Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nat Med 1996;2:412-7
  • Liu R, Paxton WA, Choe S, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996;86:367-77
  • Pfizer Labs. SELZENTRY® (maraviroc) Prescribing Information. New York, NY: August 2007
  • Carter NJ, Keating GM. Maraviroc. Drugs 2007;67:2277-88
  • Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother 2005;49:4721-32
  • Abel S, Russell D, Whitlock LA, et al. Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects. Br J Clin Pharmacol 2008;65(Suppl 1):60-7
  • Fatkenheuer G, Pozniak AL, Johnson MA, et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med 2005;11:1170-2
  • Dumond J, Patterson K, Pecha A, et al. Maraviroc (MVC) pharmacokinetics (PK) in blood plasma (BP), genital tract (GT) fluid and tissue in healthy female volunteers [abstract 135LB]. 15th Conference on Retroviruses and Opportunistic Infections; Boston, Mass. February 3-6, 2008
  • Hyland R, Dickins M, Collins C, et al. Maraviroc: in vitro assessment of drug-drug interaction potential. Br J Clin Pharmacol 2008;66:498-507
  • Abel S, Jenkins TM, Whitlock LA, et al. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):38-46
  • Abel S, Russell D, Taylor-Worth RJ, et al. Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):27-37
  • Abel S, Russell D, Whitlock LA, et al. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):19-26
  • Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 2008;359:1429-41
  • Fatkenheuer G, Nelson M, Lazzarin A, et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med 2008;359:1442-55
  • Goodrich JM, Saag M, van der Ryst E, et al. 48-week safety and efficacy of maraviroc, a novel CCR5 antagonist in combination with optimized background therapy (OBT) for the treatment of antiretroviral-experienced patients infected with dual/mixed-tropic HIV-1 [abstract LB-2]. 45th Annual Meeting of the Infectious Diseases Society of America; San Diego, California. October 4-7, 2007
  • Saag M, Ive P, Heera J, et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC]), for the treatment of antiretroviral naive patients infected with R5 HIV 1: week 48 results of the MERIT study [abstract WESS104]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; Sydney, Australia. July 22-25, 2007
  • Heera J, Saag M, Ive P, et al. Virological correlates associated with treatment failure at week 48 in the Phase 3 study of maraviroc in treatment-naïve patients [abstract 40 LB]. 15th Conference on Retroviruses and Opportunistic Infections; Boston, MA. February 3-6, 2008
  • Saag M, Heera J, Goodrich J, et al. Reanalysis of the MERIT study with the enhanced Trofile assay [abstract H-1232a]. 48th International Conference on Antimicrobial Agents and Chemotherapy; Washington, DC. October 25-28, 2008
  • Mayer H. Maraviroc: a case of severe hepatotoxicity [abstract #3]. 1st International Workshop on Targeting HIV Entry; Bethesda, Maryland. December 2-3, 2005
  • Gulick R, Su Z, Flexner C, et al. ACTG 5211: phase II study of the safety and efficacy of vicriviroc (VCV) in HIV-infected treatment-experienced subjects: 48 week results [abstract TUAB102]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; Sydney, Australia. July 22-25, 2007
  • Vandekerckhove L, Verhofstede C, Vogelaers D. Maraviroc: integration of a new antiretroviral drug class into clinical practice. J Antimicrob Chemother 2008;61:1187-90
  • Trinh L, Han D, Huang W, et al. Technical validation of an enhanced sensitivity Trofile HIV coreceptor tropism assay for selecting patients for therapy with entry inhibitors targeting CCR5. Antivir Ther 2008;13(Suppl 3):A128
  • MacArthur RD, Novak RM. Maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis 2008;47:236-41
  • Goetz M, Leduc R, Kostman J, et al. Relationship between HIV co-receptor tropism and disease progression in persons with untreated chronic HIV infection [TUPEB092]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; Sydney, Australia. July 22-25, 2007
  • Westby M, Smith-Burchnell C, Mori J, et al. Reduced maximal inhibition in phenotypic susceptibility assays indicates than viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J Virol 2007;81:2359-71
  • Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov 2005;4:236-48
  • Merck & Co., Inc. Isentress® (Raltegravir): US prescribing information. Whitehouse Station (NJ): Jan 2009
  • 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;83:293-9
  • Kassahun K, McIntosh I, Cui D, et al. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos 2007;35:1657-63
  • Iwamoto M, Kassahun K, Troyer MD, et al. Lack of a pharmacokinetic effect of raltegravir on midazolam: in vitro/in vivo correlation. J Clin Pharmacol 2008;48:209-14
  • Anderson MS, Wenning L, Moreau A, et al. Effect of raltegravir on the pharmacokinetics of oral contraceptives [abstract A-1425]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; Chicago, IL. September 17-20, 2007
  • Iwamoto M, Wenning LA, Nguyen B, et al. Effects of omeprazole on plasma levels of raltegravir. Clin Infect Dis 2009;48:489-92
  • Iwamoto M, Wenning LA, Liou SY, et al. Rifampin (RIF) modestly reduced plasma levels of MK-0518 [abstract #P299]. 8th International Congress on Drug Therapy in HIV Infection; Glasgow, Scotland. November 12-16, 2006
  • Brainard DM, Petry A, Hanley WD, et al. Doubling the dose of raltegravir does not increase trough levels in the presence of rifampin [abstract A-964]. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC. October 25-28, 2008
  • Iwamoto M, Wenning LA, Mistry GC, et al. Atazanavir modestly increases plasma levels of raltegravir in healthy subjects. Clin Infect Dis 2008;47:137-40
  • Rhame FS, Long M, Acosta E. RAL-KAL: pharmacokinetics of coadministered raltegravir and lopinavir-ritonavir in healthy adults [abstract O19]. 9th International Workshop on Clinical Pharmacology of HIV Therapy, New Orleans, LA. April 7-9, 2008
  • Wenning LA, Hanley H, Stone J, et al. Effect of tipranavir + ritonavir on pharmacokinetics of MK-0518 [abstract A-0374]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA. September 27-30, 2006
  • Wenning LA, Friedman EJ, Kost JT, et al. Lack of a significant drug interaction between raltegravir and tenofovir. Antimicrob Agents Chemother 2008;52:3253-8
  • Iwamoto M, Wenning LA, Petry AS, et al. Minimal effects of ritonavir and efavirenz on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother 2008;52:4338-43
  • Anderson MS, Kakuda TN, Hanley W, et al. Minimal pharmacokinetic interaction between the human immunodeficiency virus nonnucleoside reverse transcriptase inhibitor etravirine and the integrase inhibitor raltegravir in healthy subjects. Antimicrob Agents Chemother 2008;52:4228-32
  • Van Luin M, Colbers A, Van Ewijk-Beneken Kolmer E, et al. Raltegravir has no Influence on UGT1A4/2B7 when using lamotrigine as a phenotypic probe [abstract 693]. 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Quebec. February 8-11, 2009
  • Iwamoto M, Hanley WD, Petry AS. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother 2009 [Epub ahead of print]
  • Steigbigel RT, Cooper DA, Jumar PN, et al. Raltegravir with optimized background therapy for resistance HIV-1 infection. N Engl J Med 2008;359:339-54
  • Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008;359:355-65
  • Steigbigel R, Cooper D, Eron J, et al. 96-Week results from BENCHMRK 1 and 2, Phase III studies of raltegravir in patients failing ART with triple-class-resistant HIV [abstract 571b]. 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Quebec. February 8-11, 2009
  • Eron J, Andrade J, Zajdenverg R, et al. Switching from stable lopinavir/ritonavir-based to raltegravir-based combination art resulted in a superior lipid profile at week 12 but did not demonstrate non-inferior virologic efficacy at week 24 [abstract 70aLB].16th Conference on Retroviruses and Opportunistic Infections; Montreal, Quebec. February 8-11, 2009
  • Lennox J, Dejesus E, Lazzarin A, et al. STARTMRK, A Phase III study of the safety & efficacy of raltegravir (RAL)-based vs efavirenz (EFV)-based combination therapy in treatment-naive HIV-infected patients [abstract H-896a]. 48th International Conference on Antimicrobial Agents and Chemotherapy; Washington, DC. October 25-28, 2008
  • Lennox J, Dejesus E, Lazzarin A, et al. Subgroup analyses from STARTMRK, a phase III study of raltegravir-based vs efavirenz-based combination therapy in treatment-naïve HIV-infected patients [abstract 573]. 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Quebec. February 8-11, 2009
  • Cooper D, Steigbigel R, Lennnox J, et al. Review of Cancer Incidence in Raltegravir Clinical Trials [abstract 859]. 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Quebec. February 8-11, 2009
  • Sekar V, Lefebvre E, De Marez T, et al. Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers. Drugs R D 2007;8:241-8
  • Sekar V, Lefebvre E, Boogaerts G, et al. Pharmacokinetic interaction between the protease inhibitors TMC114 and lopinavir/ritonavir [abstract A-0367]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy San Francisco, CA. September 27-30, 2006
  • Sekar V, Lefebvre E, Marien K, et al. Pharmacokinetic interaction between darunavir and saquinavir in HIV-negative volunteers. Ther Drug Monit 2007;29:795-801
  • Sekar V, De Pauw M, Marien K, et al. No clinically significant pharmacokinetic drug-drug interaction is observed between the HIV protease inhibitor TMC114 and the non-nucleoside reverse transcriptase inhibitor efavirenz [abstract 55]. 7th International Workshop on Clinical Pharmacology of HIV Therapy, Lisbon. April 20-22, 2006
  • Boffito M, Winston A, Fletcher C, et al. Pharmacokinetics and antiretroviral response to TMC114/r and TMC125 in combination in patients with high level viral resistance [abstract 575c]. 13th Conference on Retroviruses and Opportunistic Infections Denver, CO. February 5-8, 2006
  • Kakuda TN, Scholler-Gyure M, Peeters M, et al. Pharmacokinetic interaction study with TMC125 and TMC114/rtv in HIV-negative volunteers [abstract TUPE0086]. XVI International AIDS Conference, Toronto, Canada. August 13-18, 2006
  • Van Heeswijk RP, Hoetelmans RM, Kestens D, et al. The pharmacokinetic interaction between TMC278, a next generation non-nucleoside reverse transcriptase inhibitor, and once daily darunavir/ritonavir in HIV-negative volunteers [abstract H-1042]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. September 17-20, 2007
  • Lee LS, Soon GH, Shen P, et al. Pharmacokinetics of darunavir 900mg and ritonavir 100 mg (DRV/rtv) once daily when co-administered with efavirenz 600mg once daily in healthy adult volunteers [abstract P_29]. 10th International Workshop on Clinical Pharmacology of HIV Therapy, Amsterdam. April 15-17, 2009
  • Sekar V, Spinosa-Guzman S, De Paepe E, et al. Pharmacokinetic interaction trial between darunavir in combination with low-dose ritonavir and didanosine [abstract WEPEB012]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia. July 22-25, 2007
  • Abel S, Ridgway C, Hamlin J, et al. An open, randomised, 2-way crossover study to investigate the effect of darunavir/ritonavir on the pharmacokinetics of maraviroc in healthy subjects [abstract 55]. 8th International Workshop on Pharmacology of HIV Therapy, Budapest, Hungary. April 16-18, 2007
  • Mathias A, Shen G, Enejosa J, et al. Lack of pharmacokinetic interaction between ritonavir-boosted GS-9137 (elvitegravir) and darunavir/ritonavir [abstract TUPDB03]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia. July 22-25, 2007
  • Anderson MS, Sekar V, Tomaka F, et al. Pharmacokinetic evaluation of darunavir/ritonavir and raltegravir in healthy subjects [abstract A-962]. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC. October 25-28, 2008
  • Scholler M, Hoetelmans RM, Bollen S, et al. No significant interaction between TMC125 and didanosine in healthy volunteers [abstract 29]. 6th International Workshop on Clinical Pharmacology of HIV Therapy, Quebec city, QC. April 28-30, 2005
  • Ramanathan S, Kakuda TN, Mack R, et al. Pharmacokinetics of elvitegravir and etravirine following coadministration of ritonavir-boosted elvitegravir and etravirine. Antivir Ther 2008;13:1011-7
  • Anderson MS, Kakuda TN, Hanley WD, et al. Minimal pharmacokinetic interaction between the human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor etravirine and the integrase inhibitor raltegravir in healthy subjects. Antimicrob Agents Chemother 2008;52:4228-32
  • Harris M, Zala C, Ramirez S, et al. Pharmacokinetics and safety of adding TMC125 to stable regimens of saquinavir, lopinavir, ritonavir and NRTI in HIV+ adults [abstract 575b]. 13th Conference on Retroviruses and Opportunistic Infections Denver, CO February 5-8, 2006
  • Davis J, Scholler-Gyure M, Kakuda TN, et al. An open, randomized, two-period, crossover study in two cohorts to investigate the effect of steady-state TMC125 (Etravirine) and the combination of MC125/darunavir/ritonavir on the steady-state pharmacokinetics of oral maraviroc in health subjects [abstract P4.33/02]. 11th European AIDS Conference; Madrid, Spain. October 24-27, 2007
  • Van Heeswijk RP, Hoetelmans RM, Kestens D, et al. The pharmacokinetic interaction between TMC278, a next generation non-nucleoside reverse transcriptase inhibitor, and once daily darunavir/ritonavir in HIV-negative volunteers [abstract H-1042]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy Chicago, IL. September 17-20, 2007
  • Hoetelmans R, van Heeswijk R, Kestens D, et al. Pharmacokinetic interaction between TMC 278, an investigational non-nucleoside reverse transcriptase inhibitor, and lopinavir/ritonavir in healthy volunteers [abstract 4.3/1]. 10th European AIDS Conference, Dublin, Ireland. November 17-20, 2005
  • Baede P, Piscitelli S, Graham N, Van't Klooster G. Drug interactions with TMC125, a potent next generation NNRTI [abstract A1827]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA. September 27-30, 2002
  • Scholler-Gyure M, Woodfall B, Bollen S, et al. Pharmacokinetics of amprenavir and TMC125 in HIV-infected volunteers receiving TMC125 with fosamprenavir/ritonavir [abstract A-0370]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy San Francisco, CA. September 27-30, 2006
  • Scholler-Gyure M, Kakuda TN, De Smedt G, et al. Pharmacokinetic interaction between the non-nucleoside reverse transcriptase inhibitor TMC125 and atorvastatin in HIV-negative volunteers [abstract WEPEA 106]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia. July 22-25, 2007
  • Scholler-Gyure M, Kakuda TN, De Smedt G, et al. A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV–volunteers. Br J Clin Pharmacol 2008;66:508-16
  • Scholler-Gyure M, Woodfall B, Vanaken H, et al. Lack of interaction between TMC125 and methadone [abstract TUPE0084]. XVI International AIDS Conference, Toronto, Canada. August 13-18, 2006
  • Scholler-Gyure M, Debroye C, Aharchi F, et al. No effect of TMC125 on the pharmacokinetics of oral contraceptives [abstract 57]. Eighth International Congress on Drug Therapy in HIV Infection, Glasgow. November 12-16, 2006
  • Scholler-Gyure M, Debroye C, Vyncke V, et al. Effect of TMC125 on sildenafil pharmacokinetics [abstract 45]. 7th International Workshop on Clinical Pharmacology of HIV Therapy Lisbon. April 20-22, 2006
  • Scholler-Gyure M, Kakuda TN, Van Solingen-Ristea RM, et al. No clinically relevant effect of etravirine on digoxin pharmacokinetics in HIV-negative volunteers (abstract P22). 9th International Workshop on Clinical Pharmacology of HIV Therapy New Orleans, LA. April 7-9, 2008
  • Van Heeswijk RP, Hoetelmans RM, Kestens D, et al. The pharmacokinetic interaction between ketoconazole and TMC278, an investigational non-nucleoside reverse transcriptase inhibitor in healthy, HIV-negative subjects [abstract TUPE0087]. XVI International AIDS Conference, Toronto, Canada. August 13-18, 2006
  • Crauwels HM, Van Heeswijk R, Kestens D, et al. The pharmacokinetic interaction between rifabutin and TMC278, an investigational NNRTI [abstract TUPE0080]. XVIIth International AIDS Conference, Mexico City, Mexico. August 3-8, 2008
  • Pozniak AL, Boffito M, Russell D, et al. A novel probe drug interaction study to investigate the effect of selected antiretroviral combinations on the pharmacokinetics of a single oral dose of maraviroc in HIV-positive subjects. Br J Clin Pharmacol 2008;65(Suppl 1):54-9
  • Abel S, Russell D, Whitlock LA, et al. The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):47-53

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