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Next Generation Deep Sequencing to Evaluate Viral Tropism in HIV-1 Patients Exposed to Maraviroc Add-On Therapy for 8 Days. *Rachel A. McGovern, Art F.Y. Poon, Manuel Leal, Miguel Genebat, Ezequiel Ruiz-Mateos, P. Richard Harrigan Poster #TUPDA0102. Background. X. X4. R5. Maraviroc.
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Next Generation Deep Sequencing to Evaluate Viral Tropism in HIV-1 Patients Exposed to Maraviroc Add-On Therapy for 8 Days *Rachel A. McGovern, Art F.Y. Poon, Manuel Leal, Miguel Genebat, Ezequiel Ruiz-Mateos, P. Richard Harrigan Poster #TUPDA0102
Background X X4 R5 Maraviroc • The Maraviroc Clinical Test (MCT) evaluates virological response following 8 days of exposure to MVC add-on therapy • 27 MCT patients were followed longitudinally by 454 sequence analysis • Sequences were interpreted by Geno2Phenocoreceptor algorithm (3.5 FPR cutoff); >2% X4 virus was considered non-R5 • Analyses were conducted to identify any association between the degree of viral suppression and g2p score
In those screened non-R5 by genotype MVC inhibited R5 virus, however the overall pVL remained fairly constant as non-R5 virus took over the population within 8 days. A) B) Screened R5 by deep sequencing Screened non-R5 by deep sequencing
Maraviroc exposure in patients with non-R5 virus led to strong selection for virus with an extremely low FPR A) Screened non-R5 (3.4% X4) B) Relative Fitness in the Presence of Maraviroc 0.0 0.2 0.4 0.6 0.8 1.0 0 5 10 15 20 False Positive Rate In Summary patients with non-R5 virus, when exposed to short-term maraviroc add-on therapy, demonstrated a strong selection for X4 variants having extremely low g2P scores (0 ≤ FPR < 2) in as few as 8 days.