Advanced search
Publication Cover
Expert Opinion on Pharmacotherapy Volume 9, 2008 - Issue 18
Submit an article Journal homepage
74
Views
9
CrossRef citations to date
0
Altmetric
Drug Evaluations

Developing clinical role of a CCR5 co-receptor antagonist in HIV-1 infection

David J Caldwell Assistant Professor of Clinical and Administrative Sciences ULM College of Pharmacy, 1800 Bienville Drive, Monroe, LA 71201, USA +1 318 342 1689; +1 318 342 5290; [email protected]
, PharmD AAHIVE &
Jeffery D Evans Assistant Professor of Clinical and Administrative Sciences ULM College of Pharmacy, 1725 Claiborne Ave., Shreveport, LA 71103, USA
, PharmD
Pages 3231-3242 | Published online: 10 Nov 2008

Bibliography

  • DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents Panel Roster. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available from: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf [Last accessed on 23 August 2008]
  • European AIDS Clinical Society Executive Committee, European AIDS Clinical Society (EACS). Guidelines for the clinical management and treatment of HIV infected adults in Europe. Available from: http://www.eacs.eu/guide/index.htm [Last accessed 23 August 2008]
  • Hammer SM, Eron JJ, Reiss P, et al. Antiretroviral treatment of adult HIV infection 2008 recommendations of the international AIDS Society–USA Panel. JAMA 2008;300(5):555-70
  • Isentress. EPARs for authorised medicinal products for human use. EMEA. Available from: http://www.emea.europa.eu/humandocs/Humans/EPAR/isentress/isentress.htm [Last accessed 24 August 2008]
  • Celsentri. EPARs for authorised medicinal products for human use. EMEA. Available from: http://www.emea.europa.eu/humandocs/Humans/EPAR/celsentri/celsentri.htm [Last accessed 24 August 2008]
  • Cox E. Maraviroc approval letter. Rockville, MD. Public Health Service. FDA/Department of Health and Human Services. Available from: http://www.fda.gov/cder/foi/appletter/2007/022128s000ltr.pdf [Last accessed 24 August 2008]
  • Cox E. Raltegravir approval letter. Rockville, MD. Public Health Service. FDA/Department of Health and Human Services. Available from: http://www.fda.gov/cder/foi/appletter/2007/022145s000tr.pdf [Last accessed 24 August 2008]
  • Cox E. Etravirine approval letter. Rockville, MD. Public Health Service. FDA/Department of Health and Human Services. Available from: http://www.fda.gov/cder/foi/appletter/2008/022187s000ltr.pdf [Last accessed 24 August 2008]
  • Gulick RM, Su Z, Flexner C, et al. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-infected, treatment-experienced patients: AIDS Clinical Trials Group 5211. J Infect Dis 2007;196:304-12
  • Landovitz RJ, Angel JB, Hoffman C, et al. Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naïve subjects with HIV-1 infection. J Infect Dis 2008;198:1113-22
  • 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(11):4721-32
  • Kondru R, Zhang J, Ji C, et al. Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists. Mol Pharmacol 2006;73:789-800
  • Mayer H, Van Der Ryst E, Saag M, et al. Safety and efficacy of maraviroc, a novel CCR5 antagonist, when used in combination with optimized background therapy for the treatment of antiretroviral-experienced subjects infected with dual/mixed tropic HIV-1: 24-week results of a phase 2b exploratory trial. Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract THLB0215. Available from: http://www.aids2006.org/PAG/Abstracts.aspx?AID=50985 [Last accessed 13 Oct 2008]
  • Moyle GJ, Wildfire A, Mandalia S, et al. Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis 2005;191:866-72
  • Abel S, Van Der Ryst E, Rosario MC, et al. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers. Br J Clin Pharmacol 2008;65(s1):5-18
  • 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(s1):60-7
  • 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(s1):27-37
  • Selzentry [package insert]. New York City, NY: Pfizer Inc; August 2007
  • Nelson M, Fätkenheuer G, Konourina I, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia, and North America: 24-week results [abstract 104aLB]. Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, California. Available from: http://www.retroconference.org/2007/Abstracts/30636.htm [Last accessed 26 July 2008]
  • Lalezari J, Goodrich J, De Jesus E, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b/3 study in the US and Canada [abstract 104bLB]. Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, California. Available from: http://www.retroconference.org/2007/Abstracts/30635.htm [Last accessed 26 July 2008]
  • Lalezari J, Mayer H, the MOTIVATE 1 Study Team. Efficacy and safety of maraviroc in antiretroviral treatment-experienced patients infected with CCR5-tropic HIV-1: 48-week results of MOTIVATE 1 [abstract H-718a]. Program and abstracts of the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Illinois. Available from: http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey={471F844E-DCF9-4D36-B713-6C6AC2D47CA8}&SKey= {5F5FCA3D-1CD2-4AA3-A93F-73B4E8E75F71}&MKey={D52CF5B5-E7A0-40B1-B430-CE0AC26BBA9E}& AKey={32093528-52DC-4EBE-9D80-29DAD84C92CE}',%20500,%20400); [Last accessed 26 July 2008]
  • Fätkenheuer G, Konourina I, Nelson M, et al. Efficacy and safety of maraviroc (MVC) plus optimized background therapy (OBT) in viremic, antiretroviral treatment-experienced patients infected with CCR5-tropic (R5) HIV-1 in Europe, Australia and North America (MOTIVATE 2): 48-week results [abstract PS3/5]. 11th European AIDS Conference/EACS, Madrid, 2007. Available from: http://www.eacs.eu/conference/madrid07/pdf2.php? pdf=ABS00015 [Last accessed 26 July 2008]
  • Westby M, Lewis M, Whitcomb J, et al. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol 2006;80(10):4909-20
  • Lewis M, Simpson P, Fransen S, et al. CXCR4-using virus detected in patients receiving maraviroc in the Phase III studies MOTIVATE 1 and 2 originates from a pre-existing minority of CXCR4-using virus [abstract 56]. Program and abstracts of the XVI HIV Drug Resistance Workshop; June 12-16, 2007; Barbados. Available from: http://www.intmedpress.com/Journal%20Management/display.cfm?viewinfo=3F7451620345260A0143070F4D22491C33782751545247000B5606510B330C15050003421A48470455096B00 [Last accessed 24 July 2008]
  • Van Der Ryst E, Westby M. Changes in HIV-1 co-receptor tropism for patients participating in the maraviroc MOTIVATE 1 and 2 clinical trials [abstract H-715]. Program and abstracts of the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Illinois. Available from: http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey={935091CF-D3E2-4A6C-A28C-FBC03FE760C7}&SKey={5F5FCA3D-1CD2-4AA3-A93F-73B4E8E75F71}& MKey={D52CF5B5-E7A0-40B1-B430-CE0AC26BBA9E}&AKey={32093528-52DC-4EBE-9D80-29D [Last accessed 24 July 2008]
  • Mori J, Mosley M, Lewis M, et al. Characterization of maraviroc resistance in patients failing treatment with CCR5-tropic virus in MOTIVATE 1 and MOTIVATE 2 [abstract 10]. Program and abstracts of the 16th International HIV Drug Resistance Workshop; June 12-16, 2007; Barbados. Available from: http://www.intmedpress.com/Journal%20Management/display.cfm? viewinfo= 3F7451620345260A0143070F4 D22491C33782751545247000B5606510 B330C15050003421A48470455096B00 [Last accessed 24 July 2008]
  • Kuhmann SE, Pugach P, Kunstman KJ, et al. Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. J Virol 2004;78(6):2790-807
  • Saag M, Ive P, Heera J, et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc vs 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]. Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Available from: http://www.ias2007.org/pag/Abstracts.aspx?SID=150&AID=5557 [Last accessed 24 July 2008]
  • Gulick RM, Ribaudo HJ, Shikuma CM, et al. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med 2004;350:1850-61
  • Koot M, Keet IP, Vos AH, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 1993;118:681-8
  • 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-naive patients [abstract 40LB]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://www.retroconference.org/ 2008/Abstracts/33388.htm [Last accessed 24 July 2006]
  • Ribeiro RM, Hazenger MD, Perelson AS, Davenport MP. Naïve and memory cell turnover as drivers of CCR5-to-CXCR4 tropism switch in human immunodeficiency virus type 1: implications for therapy. J Virol 2006;80:802-9
  • Maraviroc tablets NDA 22-128. Antiviral Drugs Advisory Committee Briefing Document. April 24, 2007. Available from: http://www.fda.gov/OHRMS/DOCKETS/AC/07/briefing/2007-4283b1-01-Pfizer.pdf [Last accessed 24 July 2008]
  • Nichols WG, Steel HM, Bonny T, et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother 2008;52(3):858-65
  • Bozzette SA, Ake CF, Tam HK, et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003;348:702-10
  • Currier J, Boyd F, Burtcel B, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr 2003;506-512
  • David MH, Hornung R, Fichtenbaum CJ. Ischemic cardiovascular disease in persons with human immunodeficiency virus infection. Clin Infect Dis 2002;34:98-102
  • Fichtenbaum CJ. Coronary heart disease risk, dyslipidemia, and management in HIV-infected persons. HIV Clin Trials 2004;5(6):416-33
  • De Jesus E, Walmsley S, Cohen C, et al. Fasted lipid changes after administration of maraviroc or efavirenz in combination with zidovudine and lamivudine for 48 weeks to treatment-naive HIV-infected patients [abstract 929]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://www.retroconference.org/2008/ PDFs/929.pdf [Last accessed 25 July 2008]
  • Zaitseva MB, Lee S, Rabin RL, et al. CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection. J Immunol 1998;161:3103-13
  • Carrington M, Dean M, Martin MP, O'Brien SJ. Genetics of HIV-1 infection: chemokine receptor CCR5 polymorphism and its consequences. Hum Mol Genet 1999;8(10):1939-45
  • Thomas SM, Tse DB, Ketner DS, et al. CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men. AIDS 2006;20(14):1879-83
  • Chalmet K, Van Wanzeele F, Demecheleer E, et al. Impact of Delta 32-CCR5 heterozygosity on HIV-1 genetic evolution and variability – a study of 4 individuals infected with closely related HIV-1 strains. Virology 2008;379(2):213-22
  • Gulick R, et al. ACTG 5211: Phase II study of the safety and efficacy of vicriviroc (VCV) in HIV+ treatment-experienced subjects: 48-week results [abstract TUAB102]. Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Available from: http://www.ias2007.org/pag/Abstracts.aspx?SID=48&AID=1623 [Last accessed 25 July 2008]
  • Glass WG, Mc Dermott DH, Lim JK, et al. CCR5 deficiency increases risk of symptomatic West Nile Virus Infection. J Exp Med 2006;203:35-40
  • Abel S, Russell D, Whitlock LA, et al. The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in health volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):47-53
  • Posniak 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. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in health volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):19-26
  • Abel S, Jenkins TM, Whitlock LA, et al. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in health volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):38-46
  • Isentress [package insert]. Whitehouse Station, NJ: Merck; October 2007
  • Intelence [package insert]. Raritan, Inc: Tibotec Therapeutics; January 2008
  • Cooper RA, Gatell J, Rockstroh H, et al. 48-week results from BENCHMRK-1, a Phase III study of raltegravir (RAL) in patients failing antiretroviral therapy (ART) with triple-class resistant HIV-1 [Poster 788]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://www.retroconference.org/2008/PDFs/788.pdf [Last accessed 17 Oct 2008]
  • Johnson M, Campbell T, Clotet B, et al. DUET-2: week 48 results of a Phase III randomized double-blind trial to evaluate the efficacy and safety of etravirine (ETR; TMC125) versus placebo in 591 treatment-experienced HIV-1-infected patients [Poster 791]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://www.retroconference.org/2008/PDFs/791.pdf [Last accessed 17 Oct 2008]
  • Zembower TR, Cerzenshtein L, Coleman K, Palella FJ. Severe rhabdomyolysis associated with raltegravir use [Correspondence]. AIDS 2008;22(11):1382-4
  • Low AJ, Marchant D, Brumme CJ, et al. CD4-dependent characteristics of coreceptor use and HIV type 1 V3 sequence in a large population of therapy-naive individuals. AIDS Res Hum Retroviruses 2008;24(2): 219-28
  • Dumond JB, Patterson KB, Pecha A, et al. Maraviroc pharmacokinetics in blood plasma, genital tract fluid, and tissue in healthy female volunteers [abstract 135LB]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://img.thebody.com/confs/retro2008/slides/135LB%20Dumond%20slides.pdf [Last accessed on 13 Oct 2008]
  • Whitcomb JM, Huang W, Fransen S, et al. Development and characterization of a novel singly-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother 2007;512:566-75
  • Tressler R, Valdez H, Van Der Ryst E, et al. Comparison of results from the SensiTrop vs Trofile assays on 100 samples from the maraviroc expanded access program [abstract 920a]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://www.retroconference.org/2008/PDFs/920a.pdf [Last accessed 28 July 2008]
  • Reeves J, Han D, Wilkin T, et al. An enhanced version of the Trofile HIV co-receptor tropism assay predicts emergence of CXCR4 use in ACTG5211 vicriviroc trial samples [abstract 869]. Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Massachusetts. Available from: http://www.retroconference.org/2008/Abstracts/33252.htm [Last accessed on 28 July 2008]

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.