OBJECTIVE: To investigate the rate of decline of drug resistant viruses after stopping therapy. DESIGN: Twenty-five patients receiving multiple combination therapies (mean five; range three to nine drugs) for more than 3 months were tested for HIV-1 resistance on therapy and off therapy. The sample off therapy was tested 6-175 days after stopping therapy. METHODS: Patients were tested for genotypic changes associated with drug resistance using an in-house automated DNA sequencing assay to detect resistance in the protease and reverse transcriptase genes. RESULTS: All samples tested when patients were on therapy showed evidence of drug resistance (range 1-9 mutations). The patients were divided into three groups: <2 weeks after stopping therapy, median 1.1 weeks (n = 8, group A); 2 weeks-2 months, median 6.4 weeks (n = 7, group B) and 2 months-6 months, median 12.9 weeks (n = 10, group C). Of primary mutations (protease: 30N, 461/L, 82A, 90M; reverse transcriptase: 70R, 184I/V, 215 Y/F) detected on therapy 100% remained after stopping therapy in group A; 68% remained in group B and 15% remained in group C. For secondary mutations 98% remained in group A; 99% remained in group B and 57% in group C. CONCLUSIONS: This study showed a rapid decline in detectability of the majority of primary mutations within 13 weeks of stopping combination therapy. From this data, HIV-1 resistance testing to direct patients' therapy should only be carried out when on existing therapy, or < 2 weeks off therapy, if reliable decisions are to be made relating to future combinations.
OBJECTIVE: To investigate the rate of decline of drug resistant viruses after stopping therapy. DESIGN: Twenty-five patients receiving multiple combination therapies (mean five; range three to nine drugs) for more than 3 months were tested for HIV-1 resistance on therapy and off therapy. The sample off therapy was tested 6-175 days after stopping therapy. METHODS:Patients were tested for genotypic changes associated with drug resistance using an in-house automated DNA sequencing assay to detect resistance in the protease and reverse transcriptase genes. RESULTS: All samples tested when patients were on therapy showed evidence of drug resistance (range 1-9 mutations). The patients were divided into three groups: <2 weeks after stopping therapy, median 1.1 weeks (n = 8, group A); 2 weeks-2 months, median 6.4 weeks (n = 7, group B) and 2 months-6 months, median 12.9 weeks (n = 10, group C). Of primary mutations (protease: 30N, 461/L, 82A, 90M; reverse transcriptase: 70R, 184I/V, 215 Y/F) detected on therapy 100% remained after stopping therapy in group A; 68% remained in group B and 15% remained in group C. For secondary mutations 98% remained in group A; 99% remained in group B and 57% in group C. CONCLUSIONS: This study showed a rapid decline in detectability of the majority of primary mutations within 13 weeks of stopping combination therapy. From this data, HIV-1 resistance testing to direct patients' therapy should only be carried out when on existing therapy, or < 2 weeks off therapy, if reliable decisions are to be made relating to future combinations.
Authors: Dongning Wang; Charles B Hicks; Neela D Goswami; Emi Tafoya; Ruy M Ribeiro; Fangping Cai; Alan S Perelson; Feng Gao Journal: J Virol Date: 2011-04-13 Impact factor: 5.103
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Authors: J Servais; C Lambert; E Fontaine; J M Plesséria; I Robert; V Arendt; T Staub; F Schneider; R Hemmer; G Burtonboy; J C Schmit Journal: J Clin Microbiol Date: 2001-02 Impact factor: 5.948
Authors: Bambang S Adiwijaya; Eva Herrmann; Brian Hare; Tara Kieffer; Chao Lin; Ann D Kwong; Varun Garg; John C R Randle; Christoph Sarrazin; Stefan Zeuzem; Paul R Caron Journal: PLoS Comput Biol Date: 2010-04-15 Impact factor: 4.475