Overview on Chemokine Co-Receptor-5 (CCR-5) HIV-1 Entry Inhibitors
In the 21st century, HIV-1 has turned into a noteworthy global challenge in medication. As per WHO report 2017, HIV is one of the deadliest diseases adding to an aggregate of 36.7 million contaminations until December 2016 among which 1.8 million were analyzed in 2016 itself. In 2016, 19.5 million individuals experienced to anti-retroviral treatment summing up to US$ 11 billion. With regards to rising resistance from anti-retroviral medication in HIV treatment, the advancement of most recent medication classes with a newer mode of action stays essential. The CCR5 co-receptor inhibitors suppress the fusion of HIV with the host cell by upsetting the connection of gp-120 protein with the CCR5 receptor. ThoughÂ severalCCR5 antagonists are assessed in clinical trials, just Maraviroc has been endorsed for clinical use in the treatment of HIV infected patients. The efficacy and safety profile of CCR5 adversaries with a consideration on maraviroc are assessed here in conjunction with their use in newer and developing clinical trials. In the beginning time of HIV-1 infection in the most of patients, the HIV utilizes CCR5 receptor for passage in CD4 cell of the host (CCR5-tropic infection). Maraviroc did not decrease virus load (compared to optimized background therapy) in patients with CXCR4 or dual-tropic virus. Before prescribing a CCR5 blocker HIV tropism testing is recommended. Viral tropism is defined as the capability of the viruses to enter as well as infect the host cell, and it is based on the binding capacity of the viruses to receptors on those host cells. The co-receptor type should be recognized before the treatment started with a CCR5 blocker.
Keywords: CCR5, CXCR4, HIV-1, CD4 cell, Tropism, CYP3A4.
2. Carpenter C, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, et al. Antiretroviral Therapy for HIV Infection in1998. American Medical Association. 1998; 280(1):78.
3. Nichols WG, Steel HM, Adkison K, Curtis L, Millard J, Kabeya K, et al. Hepatotoxicity observed in clinical trials of aplaviroc. Antimicrobial agents and chemotherapy. 2008; 52(3):858-865.
4. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995; 270:1811-5.
5. Cohen C, DeJesus E, Mills A, et al. Potent antiretroviral activity of the once-daily CCR5 antagonist INCB009471 over 14 days of monotherapy [Abstract TUAB106]. In: 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention 2007, Sydney, Australia.
6. Shin N, Solomon K, Wang KH, et al. INCB9471 is a non-competitive small molecule antagonist of CCR5 [Abstract H-1032]. Presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007; Chicago, IL.
7. Solomon K, Baribaud F, Shin N, et al. INCB9471 is a potent inhibitor of R5HIV-1 infection in vitro [Abstract H-1033]. Presented at: 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007; Chicago, IL.
8. Jaysuriya H, Herath KB, Ondekya JG, Polishook JD, Gerald F, Drombrowski AW, et al. Isolation and structure of antagonists of chemokine receptor (CCR5). Journal of Natural Products 2004; 67:1036-1038.
9. Baba M, Takashima K, Miyake H, et al. TAK-652 inhibits CCR5-mediated human immunodeficiency virus type 1 infection in vitro and has favorable pharmacokinetics in humans. Antimicrobial Agents and Chemotherapy. 2005; 49(11):4584-4591.
10. Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382(6593):722-5
11. 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 [abstract ThLB0215]. Presented at: XVI International AIDS Conference (IAC); 2006; Toronto [accessed on 12june2018]https://quod.lib.umich.edu/c/cohenaids/5571095.0191.008/2?view=image&size=400
12. VandekerckhoveLPR, WensingAMJ, Kaiser R, Brun-VÃ©zinet F, Clotet B, Luca AD, Dressler S, et al. European guidelines on the clinical management of HIV-1 tropism testing; Lancet Infect Dis 2011; 11:394â€“407
13. Tremblay C, Hardy I, Lalonde R, et al. HIV-1 tropism testingand clinical management of CCR5 antagonists: Quebec reviewand recommendations. Can J Infect Dis Med Microbiol 2013â€™ 24(4):202-208
14. Hamy F, Vidal V, Hubert S, Klimkait T. Hybridization-based assay andreplicative phenotyping as diagnostic platform for determination of coreceptortropism [Abstract 60]. Presented at: 5th European HIV Drug Resistance Workshop; 2007; Monte Carlo.
15. Van Baelen K, Vandenbrouke I, Rondelez E, Van Eygen V, Vermeiren H,Stuyver L. HIV-1 coreceptor usage determination in clinical isolates usingclonal and population-based genotypic and phenotypic assays. J Virol Methods. 2007; 146:61-73
16. Isaka Y, Sato A, Miki S, et al. Small amino acid changes in the V3 loop Of HIV type 2 determines the coreceptor usage for CXCR4 and CCR5.Virology. 1999â€™ 264:237-43.
17. Seclen E, Poveda E, Garrido C, et al. High sensitivity to detect X4 variantsusing specific genotypic tools in antiretroviral-experienced HIV patients suitable to CCR5 antagonists therapy. J AntimicrobChemother.2010; 65:1486-92
18. Briggs D, Tuttle D, Sleasman J, et al. Envelope V3 amino acid sequencepredicts HIV-1 phenotype (co-receptor usage and tropism for macrophages).AIDS. 2000; 14:2937-9
19. Delobel P, Nugeyre M, Cazabat M, et al. Population-based sequencingof the V3 region of env for predicting the coreceptor usage of HIV type1 quasispecies. J Clin Microbiol. 2007, 45:1572-80
20. Hoffman N, Seillier-Moiseiwitsch F, Anh J, et al. Variability in the HIV type1 gp120 Env protein linked to phenotype-associated changes in the V3loop. J Virol. 2002; 76:3852-64
21. Sierra S, Kaiser R, Thielen A, et al. Genotypic coreceptor analysis. Eur J Med Res. 2007; 12:453-62
22. 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(11):1170-2
23. Profit L.Maraviroc: the evidence for its potential in the management of HIV. Core Evidence 2007; 2(1):1-14
24. SchÃ¼rmann D, Rouzier R, Nourgarede R. SCH D: Antiviral activity of a CCR5 receptor antagonist [Abstract 140LB]. Presented at: 11th CROI; 2004; San Francisco.
25. Schurmann D, Pechardscheck C, Rouzier R, et al. SCH 417690: antiviral activity of a potent new CCR5 receptor antagonist[Abstract TuOa0205]. Presented at: 3rd IAS Conference on HIV Pathogenesis and Treatment; 2005 July 24â€“27; Rio de Janeiro, Brazil.
26. Greaves W, Landovitz R, Fatkenheuer G et al. Late virologic breakthrough in treatment-naÃ¯ve patients on a regimen of combivir plus vicriviroc [Abstract 161LB]. Presented at: XIII CROI; 2006; Denver.
27. Gulick R, Su Z, Flexner C, et al. ACTG 5211: phase 2 study of the safety and efficacy of vicriviroc in HIV-infected treatment-experienced subjects [Abstract ThLB0217].Presented at: XVI IAC; 2006; Toronto.
28. Gulick R, Su Z, Flexner C et al. Phase 2 Study of the Safety and Efficacy of Vicriviroc, a CCR5 Inhibitor, in HIV-1â€“Infected, Treatment-Experienced Patients: AIDS Clinical Trials Group 5211. J Infect Dis 2007; 196(2):304-12
29. Tremblay CL, Giguel F, Kollmann C, et al. Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro. Antimicrob Agents Chemother 2002; 46:1336â€“9.
30. 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]. Presented at: 4th IAS Conference; 2007.
31. Shah HR., Savjani JK.Recent updates for designing CCR5 antagonists as anti-retroviral agents. European Journal of Medicinal Chemistry2018, 147:115-129.
32. Lalezari J, Thompson M, Kumar P, et al. Antiviral activity and safety of 873140, a novel CCR5 antagonist, during short-term monotherapy in HIV-infected adults. AIDS 2005, 19(14): 1443â€“48
33. Crabb C. GlaxoSmithKline ends aplaviroc trials. AIDS 2006, 20: 641
34. Abel SE, VanderRyst GJ, Muirhead M, Rosario A, Edgington G, Weissgerber. Pharmacokinetics of Single and Multiple Oral Doses of UK-427,857-A Novel CCR5 Antagonist in Healthy Volunteers [Abstract 547]. Presented at: 10th CROI; February 2003; Boston, USA.
35. McHale M., et al. Overview of phase 1 and 2a safety and efficacy data of maraviroc (UK-427,857) [Abstract TuOa0204]. Presented at: The 3rd IAS Conference on HIV Pathogenesis and Treatment; 2005.
36. Lalezari J, Goodrich J, DeJesus E et al. Efficacy and Safety of Maraviroc plus Optimized Background Therapy in Viremic ART-experienced Patients Infected with CCR5tropic HIV-1: 24-Week Results of a Phase 2b/3 Study in the US and Canada[Abstract 104bLB]. Presented at: 14th CROI; 2007; Los Angeles.
37. Nelson M, Fatkenheuer G, Kounourina 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]. Presented at: 14th CROI; 2007; Los Angeles.
38. Carl J, Lenz C, Rgen J, Rockstroh K. Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges. Expert Opin. Drug Metab. Toxicol. 2010; 6(9):1139-1150
39. Schering-Plough provides update on phase II study of vicriviroc: study continues in HIV treatment experienced patients (press release). Schering-Plough Corp, March 3, 2006
40. Strizki JM, Tremblay C, Xu S, et al. Discovery and characterization of vicriviroc (SCH 417690), a R5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother 2005; 49:4911-9
41. Keung A, Sansone A, Caceres M, Kraan M, Gaillac B. Effect of Food on Bioavailability of SCH 417690 in Healthy Volunteers [abstract A-1200]. Presented at: 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2005; Washington.
42. Abel S, et al. Effect of boosted tipranavir on the pharmacokinetics of maraviroc (UK 427,857) in healthy volunteers [abstract LBPE4.3/15]. Presented at: 10th European AIDS Conference; November 17-20, 2005; Dublin.
43. Abel S, Russell D, Ridgway C, Muirhead G. Overview of the drug-drug interaction data for maraviroc (UK427,857). Presented at: 6th International Workshop on Clinical Pharmacology of HIV Therapy [Abstract 76]. April 28-30, 2005; Quebec City, Canada.
44. Muirhead G, Pozniak A, Gazzard B, Nelson M, Moyle G, Ridgway C, Taylor-Worth R, Russell D. A Novel Probe Drug Interaction Study to Investigate the Effect of Selected ARV Combinations on the Pharmacokinetics of a Single Oral Dose of UK-427,857 in HIV+ ve Subjects[Abstract 663]. Presented at: 12th Retroconference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston, USA.
45. Sansone A, Guillaume M, Kraan M, Keung A, Caceres M, Boutros T. The pharmacokinetics of SCH 417690 when administered alone and in combination with lamivudine/ zidovudine[Abstract 84]. Presented at: 6th International Workshop on Clinical Pharmacology of HIV Therapy; April 28-30, 2005; Quebec City, Canada.
46. Sansone A, Guillaume M, Kraan M, Soni P, Keung A, Boutros T. Pharmacokinetics of SCH 417690 administered alone and in combination with tenofovir [Abstract 85]. Presented at: 6th International Workshop on Clinical Pharmacology of HIV Therapy; April 28-30, 2005; Quebec City, Canada.
47. Saltzman M, Rosenberg M, Kraan M, Keung A, Boutros T, Soni P, Sansone A. Pharmacokinetics of SCH417690 administered alone or in combination with ritonavir and efavirenz in healthy volunteers [Abstract TuPe3.1.B08]. Presented at: 3rd IAS Conference on HIV Pathogenesis and Treatment; July 24-27, 2005; Rio de Janeiro, Brazil.
48. Sansone A, Keung A, Tetteh E, Weisbrot H, Martinho M, Lang S, et al.Pharmacokinetics of vicriviroc are not affected in combination with five different protease inhibitors boosted by ritonavir [Abstract 582]. Presented at: 13th Conference on Retroviruses and Opportunistic Infections; February 5-8, 2006; Denver.
49. Emmelkamp JM, Rockstroh JK. Maraviroc, risks and benefits: a review of the clinical literature. Expert Opin. Drug Saf. 2008; 7(5):559-569
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).