HIV RNA in plasma rebounds within days during structured treatment interruptions

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%); P=0.14] at day 4, 11 patients [33 of 58 samples tested (56.9%); P<0.0001] at day 8 and 12 patients [53 of 65 samples tested (81.5%); P<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. (C) 2003 Lippincott Williams Wilkins.