Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults

AIDS

Volumn 21, Issue 10, 2007, Pages 1293-1299

  Schürmann, Dirk ^a,b   Fätkenheuer, Gerd ^c   Reynes, Jacques ^d   Michelet, Christian ^e   Raffi, Francois ^f   Van Lier, Jan ^g   Caceres, Maria ^h   Keung, Anther ^h   Sansone Parsons, Angela ^h   Dunkle, Lisa M ^h   Hoffmann, Christian ⁱ  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b 3ClinicalResearch AG   (Germany)

^c UNIVERSITY OF COLOGNE   (Germany)

^d Biotrial SA   (France)

^e GUI DE CHAULIAC HOSPITAL   (France)

^f UNIVERSITÉ DE NANTES   (France)

^g PRA International USA   (Netherlands)

^h MERCK RESEARCH LABORATORIES   (United States)

ⁱ UNIVERSITY OF KIEL   (Germany)

Author keywords

AIDS; Antiretroviral therapy; CCR5 chemokine receptor antagonist; Clinical trials; Vicriviroc; Viral load

Indexed keywords

CHEMOKINE RECEPTOR CCR5 ANTAGONIST; PENICILLIN G; PLACEBO; QUINOLINE DERIVED ANTIINFECTIVE AGENT; VICRIVIROC; VIRUS RNA;

ABDOMINAL PAIN; ADULT; ANALYTICAL PARAMETERS; ANTIVIRAL ACTIVITY; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG ABSORPTION; DRUG DOSE REGIMEN; DRUG ERUPTION; DRUG FEVER; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LINEAR SYSTEM; MALE; MONOTHERAPY; NAUSEA; PHARYNGITIS; PRIORITY JOURNAL; RANDOMIZATION; RANDOMIZED CONTROLLED TRIAL; REDUCTION; SECONDARY SYPHILIS; SHORT COURSE THERAPY; STEADY STATE; TREATMENT DURATION; UPPER RESPIRATORY TRACT INFECTION; VIRUS DETECTION; VIRUS INHIBITION;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; ANTI-HIV AGENTS; CD4 LYMPHOCYTE COUNT; DRUG ADMINISTRATION SCHEDULE; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; PIPERAZINES; PYRIMIDINES; RECEPTORS, CCR5; RNA, VIRAL; TREATMENT OUTCOME; TROPISM; VIRUS REPLICATION;

EID: 34250006524     PISSN: 02699370     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAD.0b013e3280f00f9f     Document Type: Article

References (26)

1. Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984; 312:763-767.
2. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996; 272:872-877.
3. Wu L, Gerard NP, Wyatt R, Choe H, Parolin C, Ruffing N, et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 1996; 384:179-183.
4. Sattentau QJ, Moore JP. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med 1991; 174:407-415.
5. Murakami T, Freed EO. The long cytoplasmic tail of gp41 is required in a cell type-dependent manner for HIV-1 envelope glycoprotein incorporation into virions. Proc Natl Acad Sci U S A 2000; 97:343-348.
6. Wild C, Greenwell T, Matthews T. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Hum Retroviruses 1993; 9:1051-1053.
7. Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998; 4:1302-1307.
8. Tagat JR, McCombie SW, Nazareno D, Labroli MA, Xiao Y, Steensma RW, et al. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4,6-dimethyl-5-pyrimidinyl) carbonyl]- 4 - [4 - [2-methoxy-1(R)- 4-(trifluoromethyl) phenyl]ethyl-3(S)-methyl-1-piperaz inyl]-4-methylpiperidine (Sch-417690/Sch-D), a potent, highly selective, and orally bioavailable CCR5 antagonist. J Med Chem 2004; 47:2405-2408.
9. Palani A, Shapiro S, Clader JW, Greenlee WJ, Cox K, Strizki J, et al. Discovery of 4-[(Z)-(4-bromophenyl)-(ethoxyimino)-methyl]-1′- [(2,4-dimethyl-3-pyridinyl)carbonyl]-4′-methyl-1,4′-bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection. J Med Chem 2001; 44:3339-3342.
10. Strizki JM, Xu S, Wagner NE, Wojcik L, Liu J, Hou Y, et al. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc Natl Acad Sci U S A 2001; 98:12718-12723.
11. Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996; 273:1856-1862.
12. Paxton WA, Martin SR, Tse D, O'Brien TR, Skurnick J, VanDevanter NL, et al. Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nat Med 1996; 2:412-417.
13. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996; 86:367-377.
14. Strizki JM, Tremblay C, Xu S, Wojcik L, Wagner N, Gonsiorek W, et al. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother 2005; 49:4911-4919.
15. Wojcik L, Gheyas F, Ogert R, Strizki J. In vitro anti-HIV activity of SCH 417690 in combination with other antiretroviral therapies and against resistant HIV-1 strains. Presented at the 45th International Conference on Antimicrobial Agents and Chemotherapy. Washington, DC, 16-19 December 2005.[Abstract H-1096].
16. Markowitz M, Saag M, Powderly WG, Hurley AM, Hsu A, Valdes JM, et al. A preliminary study of ritonavir, an inhibitor of the HIV-1 protease, to treat HIV-1 infection. N Engl J Med 1995; 333:1534-1539.
17. Sanne I, Piliero P, Squires K, Thiry A, Schnittman S, and the AI424-007 Clinical Trial Group. Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. J Acquir Immun Defic Syndr 2003; 32:18-29.
18. Staszewski S, Katlama C, Harrer T, Massip P, Yeni P, Cutrell A, et al. A dose-ranging study to evaluate the safety and efficacy of abacavir alone or in combination with zidovudine and lamivudine in antiretroviral treatment-naive subjects. AIDS 1998; 12:F197-F202.
19. Rousseau FS, Wakeford C, Mommeja-Marin H, Sanne I, Moxham C, Harris J, et al. Prospective randomized trial of emtricitabine versus lamivudine short-term monotherapy in human immunodeficiency virus-infected patients. J Infect Dis 2003; 188:1652-1658.
20. Fatkenheuer G, Pozniak AL, Johnson MA, Plettenberg A, Staszewski S, Hoepelman AI, et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med 2005; 11:1170-1172.
21. Lalezari J, Thompson M, Kumar P, Piliero P, Davey R, Patterson K, et al. Antiviral activity and safety of 873140, a novel CCR5 antagonist, during short-term monotherapy in HIV-infected adults. AIDS 2005; 19:1443-1448.
22. Dunkle LM, Keung A, Sansone A, Strizki J. Vicriviroc is a novel, potent CCR5 inhibitor with outstanding pharmaceutic, pharmacokinetic and pharmacodynamic (PK/PD) properties. Retrovirology 2005; 2 (Suppl. I):S12.
23. 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. In: 13th Conference on Retroviruses and Opportunistic Infections. Denver, CO, 5-8 February 2006 [Abstract 582].
24. Glass WG, McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA, et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med 2006; 203:35-40.
25. Woitas RP, Ahlenstiel G, Iwan A, Rockstroh JK, Brackmann HH, Kupfer B, et al. Frequency of the HIV-protective CC chemokine receptor 5-Δ32/Δ32 genotype is increased in hepatitis C. Gastroenterology 2002; 122:1721-1728.
26. Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA 2006; 296:815-826.