Background: To evaluate time to viral rebound in patients (pts) undergoing repeated structured treatment interruptions (STIs).

Methods: Fourteen (14) chronically HIV-infected pts who were enrolled in the Swiss-Spanish-Intermittent Treatment-Trial (SSITT) underwent frequent blood sampling. Pts underwent 4 cycles of 2-week (wk) STIs, followed by 8-wk retreatment with identical antiretroviral treatment (HAART) used before STI. At the 5^th cycle, treatment was stopped for a longer period. Before each new STI, viral load had to reach < 50 copies/ml. Viral load was measured during day 0 (last day on HAART), day 4, 8, and 14 during all 5 STIs.

Results: During the first cycle, HIV-plasma RNA increased to >50 copies in 5 pts (range 67-88 copies/ml) at day 4; in 8 pts (> 100 copies/ml) at day 8; and in 12 pts (> 100 copies/ml) at day 14. Cumulative analysis of the frequency of detectable HIV-RNA at days 4, 8, and 14 compared to day 0 for all 5 cycles revealed 9 pts with viral load > 50 copies/ml (13 of 54 samples tested [24.1%], p = 0.14) at day 4, 11 pts (33 of 58 samples tested [56.9%] p < 0.0001) at day 8 and 12 pts (53 of 65 samples tested [81.5%], p < 0.0001) at day 14.

Conclusions: Significant viral replication can be induced during one week STIs, and may increase the risk of the emergence of drug resistance during long-term cycling. Therefore, short-term cycling strategies such as 1-wk on, 1-wk off treatment, although conceptually intriguing, should still be regarded as investigational, and should be restricted to rigorously controlled clinical trials ideally involving pts who have never failed treatment before.