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).


METHODS
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.
Fischer
Marek
M
Division of Infectious Diseases, University Hospital of Zürich, Switzerland.
Hafner
Roland
R
Schneider
Christine
C
Trkola
Alexandra
A
Joos
Beda
B
Joller
Helen
H
Hirschel
Bernard
B
Weber
Rainer
R
Günthard
Huldrych F
HF
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004334:Drug Administration Schedule; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D012367:RNA, Viral / Q000097:blood*; D014766:Viremia / Q000821:virology; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D012367:RNA, Viral