Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir/ritonavir in HIV-infected, therapy-naïve patients: Results of the EPIC study (CCR100136)

HIV Medicine

Volumn 10, Issue 2, 2009, Pages 116-124

  Yeni, P ^a   Lamarca, A ^b   Berger, D ^c   Cimoch, P ^d   Lazzarin, A ^e   Salvato, P ^f   Smaill, F M ^g   Teofilo, E ^h   Madison, S J ⁱ   Nichols, W G ^j   Adkison, K K ⁱ   Bonny, T ^k   Millard, J ⁱ   Mccarty, Debra ⁱ  

^a BICHAT HOSPITAL   (France)

^b Therafirst Medical Center   (United States)

^c Northstar Medical Center   (United States)

^d Center for Special Immunology   (United States)

^e VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^f Diversified Medical Practices   (United States)

^g City of Hamilton Public Health Services   (Canada)

^h Centro Hospitalar de Lisboa Central   (Portugal)

ⁱ GLAXOSMITHKLINE   (United States)

^j GLAXOSMITHKLINE   (United Kingdom)

^k W L GORE AND ASSOCIATES   (United States)

more..

Author keywords

873140; Aplaviroc; CC chemokine receptor (CCR) 5 tropic virus; HIV infection

Indexed keywords

APLAVIROC; ATAZANAVIR; LAMIVUDINE PLUS ZIDOVUDINE; LOPINAVIR PLUS RITONAVIR; VIRUS RNA;

ADOLESCENT; ADULT; AGED; ALCOHOL LIVER CIRRHOSIS; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASCITES; BRONCHITIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; FEMALE; HEPATITIS C; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERBILIRUBINEMIA; HYPERTRIGLYCERIDEMIA; IC 50; IDIOSYNCRATIC HEPATOTOXICITY; LIVER FAILURE; LIVER TOXICITY; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; NAUSEA; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PORTAL HYPERTENSION; PRIORITY JOURNAL; SIDE EFFECT; SINUSITIS; THRUSH; TREATMENT DURATION; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION;

ADULT; AGED; BENZOATES; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; MALE; MIDDLE AGED; PIPERAZINES; PYRIMIDINONES; RECEPTORS, CCR5; RITONAVIR; RNA, VIRAL; SPIRO COMPOUNDS; YOUNG ADULT;

EID: 68949137214     PISSN: 14642662     EISSN: 14681293     Source Type: Journal    
DOI: 10.1111/j.1468-1293.2008.00660.x     Document Type: Article

References (23)

1. Poignard P, Saphire EO, Parren PW, Burton DR. gp120: Biologic aspects of structural features. Annu Rev Immunol 2001; 19: 253-274.
2. Huang Y, Paxton WA, Wolinsky SM et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 1996; 2: 1240-1243.
3. Patricia D'Souza M, Harden V. Chemokines and HIV-1 second receptors. Nat Med 1996; 2: 1293-1300.
4. Maeda K, Nakata H, Miyakawa T et al. Spirodiketopiperazine-based CCR5 inhibitor, which preserves CC chemokine/CCR5 interactions and exerts potent activity against R5 HIV type 1 in vitro. J Virol 2004; 78: 8654-8662.
5. Nakata H, Maeda K, Kawano Y et al. Potent in vivo anti-R5HIV effects of AK602, a novel spirodiketopiperazine (SPD)-containing HIV-specific CCR5 inhibitor, in hu-PBMC-NOD-mice. 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, February 2003 [Abstract 564a].
6. 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: 1443-1448.
7. Sparks S, Adkison K, Shachoy-Clark A, Piscitelli S, Demarest J. Prolonged duration of CCR5 occupancy by 873140 in HIV-negative and HIV-positive W. 12th Conference on Retroviruses and Opportunistic Infections. Boston, MA, February 2005 [Abstract 77].
8. Adkison KK, Shachoy-Clark A, Fang L et al. The effects of ritonavir and lopinavir/ritonavir on the pharmacokinetics of a novel CCR5 antagonist, aplaviroc, in healthy subjects. Br J Clin Pharmacol 2006; 62: 336-344.
9. Walmsley S, Bernstein B, King M et al. Lopinavir-ritonavir vs. nelfinavir for the initial treatment of HIV infection. N Eng J Med 2002; 346: 2039-2046.
10. Murphy R, Brun R, Scott A et al. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naïve adults with HIV-1 infection: 48-week results. AIDS 2001; 15: F1-F9.
11. Gathe JC Jr, Washington M, Mayberry C, Piot D. Pilot study of the safety and efficacy of Kaletra (LPV/r) as single drug HAART in HIV+ARV naïve patients. 15th International AIDS Conference, Bangkok, Thailand, July 2004 [Abstract MoOrB1057].
12. National Institutes of Health, Division of AIDS. Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Version 1.0. Bethesda, MD: National Institutes of Health 2004.
13. Nichols WG, Steel HM, Bonny T et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother 2008; 52: 858-865.
14. Zimmerman HJ. Hepatotoxicity. New York: Appleton-Century Crofts, 1978.
15. Oldfield V, Plosker GL. Lopinavir/ritonavir: A review of its use in the management of HIV infection. Drugs 2006; 66: 1275-1299.
16. Hughes AR, Koshy BT, Lafon SW et al. Pharmacogenetic investigation of HIV medicines directed against host cellular targets. 11th International Congress on Human Genetics. Brisbane, Australia, August 2006 [Abstract/ Poster 2014].
17. Greaves W, Lanovitz R, Fatkenheuer G et al. Late virologic breakthrough in treatment-naïve patients on a regimen of Combivir + Vicriviroc. 13th Conference on Retroviruses and Opportunistic Infections. Denver, CO, February 2006 [Abstract 161LB].
18. Kitrinos KM, Irlbeck DM, LaBranche CC, Madsen HA, Demarest JF. Virologic characterization of treatment naïve subjects failing an aplaviroc-based regimen with either lamivudine/zidovudine or lopinavir/ ritonavir. 15th International Drug Resistance Workshop. Sitges, Spain, June 2006 [Abstract 21].
19. MacManus S, Yates PJ, Elston RC, White S, Richards N, Snowden W. GW433908/ritonavir once daily in antiretroviral therapy-naïve HIV-infected patients: Absence of protease resistance at 48 weeks. AIDS 2004; 18: 651-655.
20. Kempf D, King M, Bernstein B et al. Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine. J Infect Dis 2004; 181: 51-60.
21. Selzentry (maraviroc) Product Information, Pfizer Inc., New York, NY, August 2007.
22. Schering-Plough, Vicriviroc CCR5 drug, 24 week results in treatment-experienced subjects; new study with higher doses to begin. XVI International AIDS Conference. Toronto, Canada, 13-18 August, 2006. Press release.
23. Gulick RM, Su Z, Flexner C et al., for the ACTG 5211 Study Team, Phase II study of the safety and efficacy of vicriviroc (VCV) in HIV+treatment-experienced subjects. 16th International AIDS Conference. Toronto, Canada, August 2006 [Abstract THLB0217].