OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.
OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.
Authors: Sanjay Pujari; Preeyaporn Srasuebkul; Somnuek Sungkanuparph; Poh Lian Lim; Nagalingeswaran Kumarasamy; John Chuah; Ritesh N Kumar; Yi-Ming A Chen; Shinichi Oka; Jun Yong Choi; Man-Po Lee; Praphan Phanuphak; Adeeba Kamarulzaman; Christopher Lee; Zhang Fujie; Rosanna Ditangco; Vonthanak Saphonn; Thira Sirisanthana; Tuti Parwati Merati; Jeff Smith; Matthew G Law Journal: J Antivir Antiretrovir Date: 2009-11-01
Authors: Ahmed M Bayoumi; Paul G Barnett; Vilija R Joyce; Susan C Griffin; Huiying Sun; Nick J Bansback; Mark Holodniy; Gillian Sanders; Sheldon T Brown; Tassos C Kyriakides; Brian Angus; D William Cameron; Aslam H Anis; Mark Sculpher; Douglas K Owens Journal: J Acquir Immune Defic Syndr Date: 2013-12-01 Impact factor: 3.731
Authors: R Oyomopito; M P Lee; P Phanuphak; P L Lim; R Ditangco; J Zhou; T Sirisanthana; Y M A Chen; S Pujari; N Kumarasamy; S Sungkanuparph; C K C Lee; A Kamarulzaman; S Oka; F J Zhang; C V Mean; T Merati; G Tau; J Smith; P C K Li Journal: HIV Med Date: 2010-03-21 Impact factor: 3.180
Authors: Ye Ma; Decai Zhao; Lan Yu; Marc Bulterys; Matthew L Robinson; Yan Zhao; Zhihui Dou; Philippe Chiliade; Xiaoyu Wei; Fujie Zhang Journal: Clin Infect Dis Date: 2010-01-15 Impact factor: 9.079
Authors: Wasana Prasitsuebsai; Asha C Bowen; Joselyn Pang; Cees Hesp; Azar Kariminia; Annette H Sohn Journal: AIDS Patient Care STDS Date: 2010-02 Impact factor: 5.078