PURPOSE OF REVIEW: HIV entry into cells is mediated through sequential interactions between HIV envelope proteins (Env) and two cellular molecules: CD4 and a co-receptor, typically either CCR5 or CXCR4. Co-receptor preference has been associated with other viral traits; specifically, CXCR4-tropic viruses have been associated with increased host cell pathogenicity and more rapid progression of disease. Recently, much attention has been focused on the development of CCR5 and CXCR4 antagonists as antiviral agents and several are set to enter phase III trials in 2004 and 2005. The development of assays to assess the co-receptor tropism of HIV populations is critical for the optimal design and performance of clinical trials to evaluate these agents. In addition, the use of these agents in a clinical setting is likely to benefit from a reliable methodology for tropism determination prior to the selection of an optimal antiviral therapy or to evaluate continued efficacy of a regimen. RECENT FINDINGS: Tropism assays that use recombinant viruses and pseudotyped HIV are becoming more commonly employed and comparative data with standard assays have begun to be accumulated. These assays are being used to expand on earlier studies of the epidemiology and natural history of HIV tropism. In addition, tropism assays have facilitated the study of co-receptor inhibitors in vitro and in phase I and II trials. SUMMARY: The development of rapid, reliable tropism assays has been useful in advancing the development of novel antiviral agents. Defining the role of these assays in routine clinical practice will be the next important step.
PURPOSE OF REVIEW: HIV entry into cells is mediated through sequential interactions between HIV envelope proteins (Env) and two cellular molecules: CD4 and a co-receptor, typically either CCR5 or CXCR4. Co-receptor preference has been associated with other viral traits; specifically, CXCR4-tropic viruses have been associated with increased host cell pathogenicity and more rapid progression of disease. Recently, much attention has been focused on the development of CCR5 and CXCR4 antagonists as antiviral agents and several are set to enter phase III trials in 2004 and 2005. The development of assays to assess the co-receptor tropism of HIV populations is critical for the optimal design and performance of clinical trials to evaluate these agents. In addition, the use of these agents in a clinical setting is likely to benefit from a reliable methodology for tropism determination prior to the selection of an optimal antiviral therapy or to evaluate continued efficacy of a regimen. RECENT FINDINGS: Tropism assays that use recombinant viruses and pseudotyped HIV are becoming more commonly employed and comparative data with standard assays have begun to be accumulated. These assays are being used to expand on earlier studies of the epidemiology and natural history of HIV tropism. In addition, tropism assays have facilitated the study of co-receptor inhibitors in vitro and in phase I and II trials. SUMMARY: The development of rapid, reliable tropism assays has been useful in advancing the development of novel antiviral agents. Defining the role of these assays in routine clinical practice will be the next important step.
Authors: Beata Nowicka-Sans; Yi-Fei Gong; Brian McAuliffe; Ira Dicker; Hsu-Tso Ho; Nannan Zhou; Betsy Eggers; Pin-Fang Lin; Neelanjana Ray; Megan Wind-Rotolo; Li Zhu; Antara Majumdar; David Stock; Max Lataillade; George J Hanna; John D Matiskella; Yasutsugu Ueda; Tao Wang; John F Kadow; Nicholas A Meanwell; Mark Krystal Journal: Antimicrob Agents Chemother Date: 2012-04-30 Impact factor: 5.191
Authors: Jessica D Church; Wei Huang; Anthony Mwatha; Philippa Musoke; J Brooks Jackson; Danstan Bagenda; Saad B Omer; Deborah Donnell; Clemensia Nakabiito; Chineta Eure; Laura A Guay; Allan Taylor; Paul M Bakaki; Flavia Matovu; Michelle McConnell; Mary Glenn Fowler; Susan H Eshleman Journal: Curr HIV Res Date: 2010-10 Impact factor: 1.581
Authors: Ronald S Veazey; Thomas A Ketas; Per Johan Klasse; Donna K Davison; Morgan Singletary; Linda C Green; Michael L Greenberg; John P Moore Journal: Proc Natl Acad Sci U S A Date: 2008-07-22 Impact factor: 11.205