The current status of, and challenges in, the development of CCR5 inhibitors as therapeutics for HIV-1 infection

Maeda, Kenji; Nakata, Hirotomo; Ogata, Hiromi; Koh, Yasuhiro; Miyakawa, Taihei; Mitsuya, Hiroaki

doi:10.1016/j.coph.2004.07.004

Cited by 39 publications

(20 citation statements)

References 53 publications

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“…More recently, agents that target the gp120-CD4 interaction (11,15) or subsequent engagement of cellular coreceptors have been described and are being developed as antiretrovirals (4,7,16). In particular, antagonists of the cellular coreceptors, CCR5 and CXCR4, have shown promise in early-phase clinical trials (10,13,16).…”

mentioning

confidence: 99%

Discovery and Characterization of Vicriviroc (SCH 417690), a CCR5 Antagonist with Potent Activity against Human Immunodeficiency Virus Type 1

Strizki¹,

Tremblay

Xu³

et al. 2005

Antimicrob Agents Chemother

200

115

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mentioning

confidence: 99%

Discovery and Characterization of Vicriviroc (SCH 417690), a CCR5 Antagonist with Potent Activity against Human Immunodeficiency Virus Type 1

Strizki¹,

Tremblay

Xu³

et al. 2005

Antimicrob Agents Chemother

200

115

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“…Recently, with the development of coreceptor antagonists capable of blocking either the CCR5 (14,18) or the CXCR4 (18,20) coreceptor, the need for accurate HIV-phenotyping assays has increased. This is especially important in preliminary tests to screen patients for clinical trials of these agents and for monitoring the evolution of coreceptor usage under the pressure of CCR5 and/or CXCR4 antagonists (13).…”

mentioning

confidence: 99%

Determining Human Immunodeficiency Virus Coreceptor Use in a Clinical Setting: Degree of Correlation between Two Phenotypic Assays and a Bioinformatic Model

et al. 2007

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Two recombinant phenotypic assays for human immunodeficiency virus (HIV) coreceptor usage and an HIV envelope genotypic predictor were employed on a set of clinically derived HIV type 1 (HIV-1) samples in order to evaluate the concordance between measures. Previously genotyped HIV-1 samples derived from antiretroviral-naïve individuals were tested for coreceptor usage using two independent phenotyping methods. Phenotypes were determined by validated recombinant assays that incorporate either an ϳ2,500-bp ("Trofile" assay) or an ϳ900-bp (TRT assay) fragment of the HIV envelope gp120. Population-based HIV envelope V3 loop sequences (ϳ105 bp) were derived by automated sequence analysis. Genotypic coreceptor predictions were performed using a support vector machine model trained on a separate genotype-Trofile phenotype data set. HIV coreceptor usage was obtained from both phenotypic assays for 74 samples, with an overall 85.1% concordance. There was no evidence of a difference in sensitivity between the two phenotypic assays. A bioinformatic algorithm based on a support vector machine using HIV V3 genotype data was able to achieve 86.5% and 79.7% concordance with the Trofile and TRT assays, respectively, approaching the degree of agreement between the two phenotype assays. In most cases, the phenotype assays and the bioinformatic approach gave similar results. However, in cases where there were differences in the tropism results, it was not clear which of the assays was "correct." X4 (CXCR4-using) minority species in clinically derived samples likely complicate the interpretation of both phenotypic and genotypic assessments of HIV tropism.

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“…Within the last few years, the interest in HIV tropism has resurged mainly due to the appearance of promising new anti-HIV molecules that target CCR5 and CXCR4 receptors [9,10]. Given their mechanism of action, the clinical development of these compounds may require the prior knowledge of the viral tropism in a given HIV-infected individual.…”

Section: Introductionmentioning

confidence: 99%

HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors

Poveda¹,

Briz²,

Quiñones‐Mateu

et al. 2006

Aids

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The current status of, and challenges in, the development of CCR5 inhibitors as therapeutics for HIV-1 infection

Cited by 39 publications

References 53 publications

Discovery and Characterization of Vicriviroc (SCH 417690), a CCR5 Antagonist with Potent Activity against Human Immunodeficiency Virus Type 1

Discovery and Characterization of Vicriviroc (SCH 417690), a CCR5 Antagonist with Potent Activity against Human Immunodeficiency Virus Type 1

Determining Human Immunodeficiency Virus Coreceptor Use in a Clinical Setting: Degree of Correlation between Two Phenotypic Assays and a Bioinformatic Model

HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors

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