Response to Vicriviroc in Treatment-Experienced Subjects, as Determined by an Enhanced-Sensitivity Coreceptor Tropism Assay: Reanalysis of AIDS Clinical Trials Group A5211

• Published in: The Journal of infectious diseases Vol. 200; no. 11; pp. 1724 - 1728
• Main Authors: Su, Zhaohui, Gulick, Roy M., Krambrink, Amy, Coakley, Eoin, Hughes, Michael D., Han, Dong, Flexner, Charles, Wilkin, Timothy J., Skolnik, Paul R., Greaves, Wayne L., Kuritzkes, Daniel R., Reeves, Jacqueline D.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 01.12.2009; University of Chicago Press; Oxford University Press
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; AIDS; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CCR5 Receptor Antagonists; CD4 Lymphocyte Count; Clinical trials; Double-Blind Method; Grants; HIV; HIV 1; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - metabolism; HIV-1 - physiology; HIV/AIDS; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Medical sciences; Pharmacology. Drug treatments; Piperazines - therapeutic use; Pyrimidines - therapeutic use; Receptors; RNA; RNA, Viral - metabolism; Sensitivity and Specificity; Statistics, Nonparametric; Tropisms; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Tropism - drug effects; Viral Tropism - physiology; Virology; Viruses; Human; Tropism; Immunopathology; Antiretroviral agent; AIDS; Immune deficiency; Infection; Sensitivity; Treatment; Viral disease; Antiviral; Clinical trial; Vicriviroc
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/648090

The enhanced-sensitivity Trofile assay (Monogram Biosciences) was used to retest coreceptor use at both study screening and study entry for 118 treatment-experienced subjects in AIDS Clinical Trials Group A5211 who had CCR5-tropic (R5) virus detected by the original Trofile assay at study screening. Among 90 recipients of vicriviroc, a significantly (P<.001) greater mean reduction in HIV-1 RNA was observed in 72 subjects with R5 virus versus 15 subjects reclassified as having dual/mixed-tropic viruses at screening: −1.11 versus −0.09 log10 copies/mL at day 14 and −1.91 versus −0.57 log10 copies/mL at week 24, respectively. Results suggest that the enhanced-sensitivity assay is a better screening tool for determining patient eligibility for CCR5 antagonist therapy