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ResistancetoHIVtherapy-EACSEuropeanAIDSClinical：抗HIV治疗的EACS欧洲艾滋病临床.ppt
ITT analysis RAL arm: Integrase from 12/39 VFs = 4 RALR*; RT in 13/39 VFs = 5 FTCR EFV arm: RT from 9/45 VFs = 5 EFVR; 2 FTCR * NNRTI resistance mutations emerge rapidly in patients with detectable viraemia during NNRTI therapy Single NNRTI mutations can cause high-level NNRTI resistance and cross-resistance Resistance mutations continue to accumulate * * Viral rebound was most apparent in individuals who had more than one NRTI mutation at baseline. In contrast, the subset of patients with no NRTI mutations demonstrated a more durable viral load suppression of about 1.75 log10 copies/mL below baseline as of week 16. Those patients with four or more NRTI mutations at baseline showed virtually no response to etravirine. The number of NNRTI mutations also had an impact on etravirine efficacy, and there was transient suppression in some individuals who had just one NNRTI mutation at baseline. * * Pyrophosphate can also be an acceptor Antagonised by M184V, K65R, L74V * * * The clinical implications of these observations can be summarised as follows * The clinical implications of these observations can be summarised as follows * Ongoing Activity of ETV with a weak backbone Study TMC125-C227: 2 NRTIs + ETV or PI Ruxrungtham, HIV Med 2008 ART-experienced, PI-naive patients with documented NNRTI resistance The genetic barrier of PIs in vitro De Meyer, Antimicrob Agents Chemother 2005; De Meyer, IHDRW 2006 Time (days) Increase in PI selection concentration 0 50 100 150 200 250 300 350 400 450 0 100 300 500 700 900 1100 DRV (R41T, K70E) RTV (G16E, M46I, V82F, I84V) SQV (G48V, A71V, G73S, I84V, L90M) NFV (L10F, D30N, R41K, K45I, M46I, V77I, I84V, N88D) APV (L10F, V32I, L33F, M46I, I47V, I50V) LPV (L10F, L23I, M46I, I50V, I54V, L63P, V82A) TPV (L33V, M46L, V82T) ATV (L10F, V32I, M46I, I62V, A71V, I84V, N88S) Emergence of PI mutation with DRV/r vs LPV/r TITAN study: OBR + DRV/r or LPV/r 1Johnson et al. Top HIV Med 2007; 0 10 20 30 Primary PI mutations1 NRTI RAMs1 VFs w
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