TILT: a randomized controlled trial of interruption of antiretroviral therapy with or without interleukin-2 in HIV-1 infected individuals.
OBJECTIVE
We aimed to see if structured treatment interruption (STI) could be supported safely with the use of two cycles of IL-2 (4.5 MIU q12h subcutaneously 5 days) before STI to prolong the time before therapy restarted.


METHODS
Subjects were randomly allocated to either A - continuous ART; B - continue for 9 weeks, then STI; restart with the same ART when the CD4 count falls below 200 cells; or C - two cycles of IL-2, 8 weeks apart, while still on ART; at week 9 stop ART and use a new cycle of IL-2 alone whenever the CD4 count falls < 300 cells. Patients were followed until week 105.


RESULTS
86 mostly white middle aged homosexual men with a baseline median CD4 count of 754 cells/ml (range 240-1400) and a nadir CD4 count of 268 cells/ml (range 62-822) enrolled. By 96 weeks there was a 66% probability of having restarted ART in arm B compared with 34% in arm C (p = 0.002; log rank test). New drugs were used in 60% in arm A, 57% in arm B and 45% in arm C. 4 subjects had a dose modification in the first cycle due to toxicity with 2 interrupting. There were 39 SAEs with 21 in arm C. There were no deaths.


CONCLUSIONS
The primary aim of the trial was to gain experience in using IL-2. IL-2 delayed restarting drugs and fewer new drugs were used.
Angus
Brian
B
Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK. brian.angus@ndm.ox.ac.uk
Lampe
Fiona
F
Tambussi
Guiseppe
G
Duvivier
Claudine
C
Katlama
Christine
C
Youle
Mike
M
Williams
Ian
I
Clotet
Bonaventura
B
Fisher
Martin
M
Post
Frank A
FA
Babiker
Abdul
A
Phillips
Andrew
A
D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006716:Homosexuality; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019562:Viral Load
D044966:Anti-Retroviral Agents; D007376:Interleukin-2