Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
G0000198
Study information
Scientific title
Acronym
TILT
Study hypothesis
Primary: To gain experience in antiretroviral therapy interruptions in patients with viral suppression and increased CD4 count, with and without use of Interleukin-2 (IL-2). In particular, to test the ability to maintain the CD4 count at a level above 150/mm3 during interruption, to evaluate the length of time off therapy that can be safely achieved and to evaluate the ability to "re-suppress" viral load if and when antiretroviral therapy is restarted. This information will be used to guide the design of a larger trial.
Secondary: To obtain preliminary data comparing the three strategies with regard to:
1. CD4 count decline to less than 150/mm to the power of three or new Acquired Immume Deficiency Symdrome (AIDS) disease or death
2. Virological failure of therapy (viral load greater than 1000 after having been on antiretroviral therapy for over 16 weeks) by two years
3. Changes in levels of lactates, lipids and bicarbonates
4. Quality of life using the Medical Outcomes Study health status questionnaire for HIV (MOS-HIV)
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Human Immunodeficiency Virus (HIV), Acquired Immune Deficiency Syndrome (AIDS)
Intervention
An open, randomised, three arm, controlled trial to study interruption of antiretroviral therapy with or without IL-2 therapy, in individuals with HIV-1 infection and nadir CD4 cell counts greater than 100 x 10^6/1, current CD4 count greater than 300 x 10^6/1 and currently receiving antiretrovirals and with a viral load less than 50 copies/ml for greater than three months.
Participants will be randomly allocated 1:1:1 ratio to either:
1. Continue with antiretroviral therapy. If drugs need to be switched for any reason, this should be done without a complete interruption, or
2. Interrupt antiretroviral therapy. Restart with the same regimen when the clinician and patient feel this is warranted. Treatment should certainly be restarted before the CD4 count falls below 200/mm^3. Further treatment interruptions should be considered when viral load is less than 50 for 12 weeks or more and if CD4 count is more than or equal to 300/mm^3, or
3. Give two cycles of IL-2, eight weeks apart, while still on antiretroviral therapy. Then interrupt antiretroviral therapy. Use new cycles of IL-2 and/or reintroduction of antiretroviral therapy if the clinician and patient feel that this is warranted.
New cycles of IL-2 and/or antiretroviral therapy should certainly be given before the CD4 count falls below 200/mm^3.
Last patient will complete follow up in July 2006.
Intervention type
Drug
Phase
Not Specified
Drug names
interLeukin-Two
Primary outcome measure
1. CD4 decline to les than 100 or new AIDS disease after death
2. Virological failure of therapy at two years after baseline
3. Virological failure of therapy at any time during the two year period after randomisation
4. Changes in levels of total cholesterol
5. Changes in severity of lipodystrophy/ quality of life
6. Incidence of grade three or four adverse
Secondary outcome measures
Not provided at time of registration
Overall trial start date
20/02/2001
Overall trial end date
31/08/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. HIV seropositive
2. Adult (18 years or older) HIV-infected therapy naïve patients
3. On Highly Active Anti-retroviral Therapy (HAART) (more than or equal to three ARTs of any of the three main classes) with viral load less than 50 copies/mL for 12 weeks or more
4. CD4 count nadir more than 50/mm^3
5. CD4 lymphocyte count more than or equal to 300/mm^3
6. Signed informed consent obtained
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
90 - Closed to recruitment - in follow-up
Participant exclusion criteria
1. Patients on hydroxyurea or interferons or any immunomodulating agent besides IL-2
2. Age less than 16
3. Prior IL-2 therapy
4. Use of any approved or experimental antiretroviral drug within four months prior to study therapy
5. Concurrent malignancy other than mucocutaneos Kaposi sarcoma or malignancy treated within the past five years
6. Any concurrent or history of AIDS defining illness
7. Use of systemic corticosteroids, chemotherapy or experimental cytotoxic drugs within four weeks prior to study therapy
8. Use of any agent approved or experimental with clinically significant immunomodulatory effects
9. Any Central Nervous System (CNS) abnormality that requires treatment with anti-seizure medication
10. Patients with current or historical Crohn's disease, psoriasis or other autoimmune/inflammatory diseases with potential life threatening complications
11. Pregnant or lactating women
12. Use of recreational drugs/alcohol that in the opinion of the investigator would affect patient safety and/or compliance
13. Patients with any serious psychiatric, medical and/or cognitive disturbance or illness that in the opinion of the investigator may affect safety, compliance or ability to provide written informed consent
Recruitment start date
20/02/2001
Recruitment end date
31/08/2006
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Department of Thoracic Medicine
London
NW3 2QG
United Kingdom
Sponsor information
Organisation
Medical Research Council (MRC) (UK)
Sponsor details
20 Park Crescent
London
W1B 1AL
United Kingdom
+44 (0)20 7636 5422
clinical.trial@headoffice.mrc.ac.uk
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (MRC) (UK)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18356603
Publication citations
-
Results
Angus B, Lampe F, Tambussi G, Duvivier C, Katlama C, Youle M, Williams I, Clotet B, Fisher M, Post FA, Babiker A, Phillips A, , TILT: a randomized controlled trial of interruption of antiretroviral therapy with or without interleukin-2 in HIV-1 infected individuals., AIDS, 2008, 22, 6, 737-740, doi: 10.1097/QAD.0b013e3282f511f1.