OBJECTIVE: To evaluate time to viral rebound in patients undergoing repeated structured treatment interruptions (STI). METHOD: Fourteen chronically HIV-infected patients enrolled in the Swiss-Spanish Intermittent Treatment Trial (SSITT) underwent frequent blood sampling. Patients underwent four cycles of 2-week STI, followed by 8-week retreatment with the identical antiretroviral treatment (HAART) used before STI. At the fifth cycle, treatment was stopped for a longer period. Before each new STI, plasma viral load (VL) had to reach < 50 copies/ml. VL was measured during day 0 (last day on HAART) and on days 4, 8 and 14 during all five STI. RESULTS: During the first cycle, plasma HIV RNA increased to > 50 copies/ml (range, 67-88) in five patients at day 4, in eight patients (> 100 copies/ml) at day 8 and in 12 patients (> 100 copies/ml) at day 14. Cumulative analysis of the frequency of detectable HIV RNA at days 4, 8 and 14 compared with day 0 for all five cycles revealed nine patients with VL > 50 copies/ml [13 of 54 samples tested (24.1%); = 0.14] at day 4, 11 patients [33 of 58 samples tested (56.9%); < 0.0001] at day 8 and 12 patients [53 of 65 samples tested (81.5%); < 0.0001] at day 14. CONCLUSIONS: Significant viral replication can be induced during 1 week STI, and this may increase the risk of the emergence of drug resistance during long-term cycling. Therefore, short-term cycling strategies such as 1-week-on, 1-week-off treatment, although conceptually intriguing, should still be regarded as investigational and should be restricted to rigorously controlled clinical trials ideally involving patients who have never failed treatment before.
OBJECTIVE: To evaluate time to viral rebound in patients undergoing repeated structured treatment interruptions (STI). METHOD: Fourteen chronically HIV-infectedpatients enrolled in the Swiss-Spanish Intermittent Treatment Trial (SSITT) underwent frequent blood sampling. Patients underwent four cycles of 2-week STI, followed by 8-week retreatment with the identical antiretroviral treatment (HAART) used before STI. At the fifth cycle, treatment was stopped for a longer period. Before each new STI, plasma viral load (VL) had to reach < 50 copies/ml. VL was measured during day 0 (last day on HAART) and on days 4, 8 and 14 during all five STI. RESULTS: During the first cycle, plasma HIV RNA increased to > 50 copies/ml (range, 67-88) in five patients at day 4, in eight patients (> 100 copies/ml) at day 8 and in 12 patients (> 100 copies/ml) at day 14. Cumulative analysis of the frequency of detectable HIV RNA at days 4, 8 and 14 compared with day 0 for all five cycles revealed nine patients with VL > 50 copies/ml [13 of 54 samples tested (24.1%); = 0.14] at day 4, 11 patients [33 of 58 samples tested (56.9%); < 0.0001] at day 8 and 12 patients [53 of 65 samples tested (81.5%); < 0.0001] at day 14. CONCLUSIONS: Significant viral replication can be induced during 1 week STI, and this may increase the risk of the emergence of drug resistance during long-term cycling. Therefore, short-term cycling strategies such as 1-week-on, 1-week-off treatment, although conceptually intriguing, should still be regarded as investigational and should be restricted to rigorously controlled clinical trials ideally involving patients who have never failed treatment before.
Authors: Beda Joos; Marek Fischer; Herbert Kuster; Satish K Pillai; Joseph K Wong; Jürg Böni; Bernard Hirschel; Rainer Weber; Alexandra Trkola; Huldrych F Günthard Journal: Proc Natl Acad Sci U S A Date: 2008-10-20 Impact factor: 11.205
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Authors: Paula Lerner; Moraima Guadalupe; Richard Donovan; Jason Hung; Jason Flamm; Thomas Prindiville; Sumathi Sankaran-Walters; Michael Syvanen; Joseph K Wong; Michael D George; Satya Dandekar Journal: J Virol Date: 2011-02-23 Impact factor: 5.103
Authors: Adrian Schmid; Sara Gianella; Viktor von Wyl; Karin J Metzner; Alexandra U Scherrer; Barbara Niederöst; Claudia F Althaus; Philip Rieder; Christina Grube; Beda Joos; Rainer Weber; Marek Fischer; Huldrych F Günthard Journal: PLoS One Date: 2010-10-12 Impact factor: 3.240
Authors: Sona Budhiraja; Marylinda Famiglietti; Alberto Bosque; Vicente Planelles; Andrew P Rice Journal: J Virol Date: 2012-11-14 Impact factor: 5.103