HIV entry: new insights and implications for patient management

被引:15
作者
Hughes, Amelia [1 ]
Nelson, Mark [1 ]
机构
[1] Chelsea & Westminster NHS Fdn Trust, St Stephens Ctr, London SW10 9NH, England
关键词
attachment inhibitors; CCR5; antagonists; fusion inhibitors; HIV entry inhibitors; HIV tropism; CHEMOKINE RECEPTOR USE; CORECEPTOR USAGE; MONOCLONAL-ANTIBODY; ANTIVIRAL ACTIVITY; CXCR4; CORECEPTORS; CLINICAL-COURSE; BROAD-SPECTRUM; SUBTYPE E; CCR5; EPIDEMIOLOGY;
D O I
10.1097/QCO.0b013e3283213093
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose of review The discovery of the chemokine coreceptors CCR5 and CXCR4, essential for HIV entry, provoked over a decade of research into the mechanism of HIV entry and potential targets for treatment and prevention of HIV. This review article reports the recent published data regarding licensed and investigational HIV entry inhibitors including CCR5 and CXCR4 antagonists, fusion inhibitors and attachment inhibitors. Recent findings The results from the maraviroc and vicriviroc clinical trials are reported, showing the efficacy and safety of CCR5 antagonists in treatment of multidrug resistant HIV. The poor sensitivity of the original screening tropism assay is associated with virological failure in individuals mislabelled R5 tropic who receive CCR5 antagonists. Reanalyses of clinical trials using a superior screening assay are in progress. Superior immunological restoration is seen with CCR5 antagonists that may be of benefit to individuals with discordant CD4 cell response with antiretroviral therapy and to those with severe immunosuppression. Summary Research and development of HIV entry inhibitors is ongoing and provides new classes of drug that can be used in the treatment of HIV. Clinical trials will soon commence to assess the benefit of CCR5 antagonists in immune reconstitution and other therapeutic uses.
引用
收藏
页码:35 / 42
页数:8
相关论文
共 73 条
[51]  
PAXINOS E, 2002, 42 ANN INT C ANT AG
[52]  
PETT A, 2008, 15 C RETR OPP INF 3
[53]  
PHILLIPS A, 2008, 15 C RETR OPP INF 3
[54]  
REEVES J, 2008, 15 C RETR OPP INF 3
[55]  
SAAG M, 2007, 4 IAS C 22 25 JUL 20
[56]  
SAAG M, 2007, 14 C RETR OPP INF 25
[57]  
SAAG M, 2007, 4 IAS C HIV PATH TRE
[58]   The case for selection at CCR5-Δ32 [J].
Sabeti, PC ;
Walsh, E ;
Schaffner, SF ;
Varilly, P ;
Fry, B ;
Hutcheson, HB ;
Cullen, M ;
Mikkelsen, TS ;
Roy, J ;
Patterson, N ;
Cooper, R ;
Reich, D ;
Altshuler, D ;
O'Brien, S ;
Lander, ES .
PLOS BIOLOGY, 2005, 3 (11) :1963-1969
[59]   Co-receptor antagonists as HIV-1 entry inhibitors [J].
Shaheen, F ;
Collman, RG .
CURRENT OPINION IN INFECTIOUS DISEASES, 2004, 17 (01) :7-16
[60]  
Sierra S, 2007, EUR J MED RES, V12, P453