PURPOSE OF REVIEW: HIV-1 entry into target cells is a complex multistage process involving the envelope glycoprotein, primary cellular receptor CD4, and at least two main cellular coreceptors, CCR5 and CXCR4. The identification of the HIV-1 coreceptors led to the rapid development of several drug candidates that selectively block this interaction, that is, CCR5 or CXCR4 antagonists. Here, we review different methodologies used to determine the ability of the virus to use one or both coreceptors and their potential role in managing HIV-infected individuals treated with these novel drugs. RECENT FINDINGS: Most commercially available HIV-1 tropism assays are cell-based (phenotypic) tests, which use different methodologies to generate env-recombinant viruses and distinct detection systems. On the other hand, a large effort is being devoted to develop more robust bioinformatic (genotypic) tools that may expedite HIV-1 tropism assays without compromising their accuracy. The main goal, however, continues to be to improve the sensitivity to detect minor CXCR4-tropic variants within the in-vivo HIV-1 quasispecies. SUMMARY: An accurate determination, and perhaps quantification, of HIV-1 coreceptor usage is necessary for the successful management of HIV-infected individuals in the new era of entry inhibitors. Further studies, aimed to the development of novel methodologies, are essential for the success of this new class of drugs.
PURPOSE OF REVIEW: HIV-1 entry into target cells is a complex multistage process involving the envelope glycoprotein, primary cellular receptor CD4, and at least two main cellular coreceptors, CCR5 and CXCR4. The identification of the HIV-1 coreceptors led to the rapid development of several drug candidates that selectively block this interaction, that is, CCR5 or CXCR4 antagonists. Here, we review different methodologies used to determine the ability of the virus to use one or both coreceptors and their potential role in managing HIV-infected individuals treated with these novel drugs. RECENT FINDINGS: Most commercially available HIV-1 tropism assays are cell-based (phenotypic) tests, which use different methodologies to generate env-recombinant viruses and distinct detection systems. On the other hand, a large effort is being devoted to develop more robust bioinformatic (genotypic) tools that may expedite HIV-1 tropism assays without compromising their accuracy. The main goal, however, continues to be to improve the sensitivity to detect minor CXCR4-tropic variants within the in-vivo HIV-1 quasispecies. SUMMARY: An accurate determination, and perhaps quantification, of HIV-1 coreceptor usage is necessary for the successful management of HIV-infected individuals in the new era of entry inhibitors. Further studies, aimed to the development of novel methodologies, are essential for the success of this new class of drugs.
Authors: Luke C Swenson; Theresa Mo; Winnie W Y Dong; Xiaoyin Zhong; Conan K Woods; Mark A Jensen; Alexander Thielen; Douglass Chapman; Marilyn Lewis; Ian James; Jayvant Heera; Hernan Valdez; P Richard Harrigan Journal: J Infect Dis Date: 2011-01-15 Impact factor: 5.226
Authors: Jan Weber; Ana C Vazquez; Dane Winner; Richard M Gibson; Ariel M Rhea; Justine D Rose; Doug Wylie; Kenneth Henry; Alison Wright; Kevin King; John Archer; Eva Poveda; Vicente Soriano; David L Robertson; Paul D Olivo; Eric J Arts; Miguel E Quiñones-Mateu Journal: J Clin Microbiol Date: 2013-03-13 Impact factor: 5.948