Synergistic Combinations of the CCR5 Inhibitor VCH-286 with Other Classes of HIV-1 Inhibitors

被引:6
作者
Asin-Milan, Odalis [1 ,2 ]
Sylla, Mohamed [1 ]
El-Far, Mohamed [1 ]
Belanger-Jasmin, Genevieve [1 ]
Haidara, Alpha [1 ]
Blackburn, Julie [1 ]
Chamberland, Annie [1 ]
Tremblay, Cecile L. [1 ,2 ,3 ]
机构
[1] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ, Canada
[2] Univ Montreal, Fac Med, Dept Microbiol & Immunol, Montreal, PQ, Canada
[3] Inst Natl Sante Publ Quebec, Lab Sante Publ Quebec, Montreal, PQ, Canada
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL-MOLECULE INHIBITOR; ENTRY INHIBITORS; POTENT; INFECTION; MARAVIROC; INDIVIDUALS; PROGRESSION; ANTAGONISTS; VICRIVIROC;
D O I
10.1128/AAC.03630-14
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Here, we evaluated the in vitro anti-HIV-1 activity of the experimental CCR5 inhibitor VCH-286 as a single agent or in combination with various classes of HIV-1 inhibitors. Although VCH-286 used alone had highly inhibitory activity, paired combinations with different drug classes led to synergistic or additive interactions. However, combinations with other CCR5 inhibitors led to effects ranging from synergy to antagonism. We suggest that caution should be exercised when combining CCR5 inhibitors in vivo.
引用
收藏
页码:7565 / 7569
页数:5
相关论文
共 32 条
[1]   Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation [J].
Allers, Kristina ;
Huetter, Gero ;
Hofmann, Joerg ;
Loddenkemper, Christoph ;
Rieger, Kathrin ;
Thiel, Eckhard ;
Schneider, Thomas .
BLOOD, 2011, 117 (10) :2791-2799
[2]   V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc [J].
Berro, Reem ;
Klasse, Per Johan ;
Moore, John P. ;
Sanders, Rogier W. .
VIROLOGY, 2012, 427 (02) :158-165
[3]  
Bhopale Girish M, 2012, Recent Pat Antiinfect Drug Discov, V7, P45
[4]   HIV entry inhibitors: mechanisms of action and resistance pathways [J].
Briz, V ;
Poveda, E ;
Soriano, V .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 57 (04) :619-627
[5]  
Chou T.C., 1991, MEDIAN EFFECT PRINCI
[6]   QUANTITATIVE-ANALYSIS OF DOSE-EFFECT RELATIONSHIPS - THE COMBINED EFFECTS OF MULTIPLE-DRUGS OR ENZYME-INHIBITORS [J].
CHOU, TC ;
TALALAY, P .
ADVANCES IN ENZYME REGULATION, 1984, 22 :27-55
[7]   Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies [J].
Chou, Ting-Chao .
PHARMACOLOGICAL REVIEWS, 2006, 58 (03) :621-681
[8]   Change in coreceptor use correlates with disease progression in HIV-1-infected individuals [J].
Connor, RI ;
Sheridan, KE ;
Ceradini, D ;
Choe, S ;
Landau, NR .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (04) :621-628
[9]   INCREASED VIRAL BURDEN AND CYTOPATHICITY CORRELATE TEMPORALLY WITH CD4+ T-LYMPHOCYTE DECLINE AND CLINICAL PROGRESSION IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED INDIVIDUALS [J].
CONNOR, RI ;
MOHRI, H ;
CAO, YZ ;
HO, DD .
JOURNAL OF VIROLOGY, 1993, 67 (04) :1772-1777
[10]   CCR5 antagonism in HIV infection: ways, effects, and side effects [J].
Corbeau, Pierre ;
Reynes, Jacques .
AIDS, 2009, 23 (15) :1931-1943