Phase II/III Study Evaluating the Effect of IL-2 on Preservation of the CD4 T-Lymphocytes After Interruption of Antiretroviral Treatment in HIV-Infected Patients With CD4 T-Lymphocyte Count Greater Than 500 Cells/mm3 Who Received Antiretroviral Tx (ILIADE)

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ClinicalTrials.gov Identifier: NCT00071890

Recruitment Status : Completed

First Posted : November 4, 2003

Results First Posted : October 5, 2010

Last Update Posted : October 5, 2010

Sponsor:

Collaborator:

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Information provided by:

National Institutes of Health Clinical Center (CC)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	HIV Infections
Interventions	Drug: Interleukin 2 Drug: HAART Drug: Treatment interruption
Enrollment	148

Participant Flow

Recruitment Details	From November 2003 to July 2006, 148 patients were randomized (81 in the IL-2 arm and 67 in the control arm in one centre of the NIH (USA) and 21 centres of the ANRS network (France).
Pre-assignment Details	31 patients were not included because : CD4 below 500 (n=8), patient decision (n=6), HIV RNA < 50 copies/ml (n=5), neutropenia or high bilirubin(n=3), CD4 nadir below 200 (n=2),other diseases (n=2), AIDS (n=1), other reason (n=4)


Arm/Group Title	Interleukin-2 Group	Control Group
Arm/Group Description	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Arm/Group Description	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Period Title: Overall Study
Started	81 ^[1]	67 ^[2]
Completed	81 ^[3]	67 ^[4]
Not Completed	0	0
[1] 3 patients did not received Interleukin-2 [2] 1 patients stopped HAART at week 0 [3] 1 withdrawal 1 death 81 patients analysed [4] 1 withdrawal 1 lost of follow-up 1 death 67 patients analysed

Baseline Characteristics

Arm/Group Title		Interleukin-2 Group	Control Group	Total
Arm/Group Description		HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)	Total of all reporting groups
Arm/Group Description		HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)	Total of all reporting groups
Overall Number of Baseline Participants		81	67	148
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	81 participants	67 participants	148 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	81 100.0%	66 98.5%	147 99.3%
	>=65 years	0 0.0%	1 1.5%	1 0.7%
Age Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	81 participants	67 participants	148 participants
		42 (8)	44 (9)	43 (8)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	81 participants	67 participants	148 participants
	Female	15 18.5%	13 19.4%	28 18.9%
	Male	66 81.5%	54 80.6%	120 81.1%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	81 participants	67 participants	148 participants
France		77	63	140
United States		4	4	8
CD4 at inclusion Median (Inter-Quartile Range) Unit of measure: Cells per mm3
	Number Analyzed	81 participants	67 participants	148 participants
		770 (646 to 876)	735 (625 to 834)	747 (637 to 851)
CD4 nadir Median (Inter-Quartile Range) Unit of measure: Cells per mm3
	Number Analyzed	81 participants	67 participants	148 participants
		326 (264 to 438)	328 (259 to 355)	326 (263 to 411)

Outcome Measures

1.Primary Outcome


Title	Proportion of Patients Without Failure of Strategy From Week 0 to Week 72
Description	A failure of strategy is...
Description	A failure of strategy is defined on the first occurrence of one of the following events: CD4 T-lymphocyte count becomes < 350 cells/mm3 between Wk0 and Wk72 (count confirmed by a 2nd measurement after 2-4 weeks Planned interruption of therapy at Wk24 cannot be done for any reason; Anti-retroviral treatment is restarted between Wk24 and Wk72 for any reason Subject experiences clinical progression of HIV infection to a stage C AIDS diagnosis (appendix I) Subject expires between Wk0 and Wk72 (whatever the cause of death) Subject is lost to follow up
Time Frame	week 72

Outcome Measure Data

Analysis Population Description

Intent to treat analysis, missing = failure.


Arm/Group Title	Interleukin-2 Group	Control Group
Arm/Group Description:	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Arm/Group Description:	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Overall Number of Participants Analyzed	81	67
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Pourcentage
	73 (63 to 83)	55 (43 to 67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Interleukin-2 Group, Control Group
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.025
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

2.Secondary Outcome


Title	Changes in CD4 Counts at Week 72
Description	[Not Specified]
Description	[Not Specified]
Time Frame	week 72

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Interleukin-2 Group	Control Group
Arm/Group Description:	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Arm/Group Description:	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Overall Number of Participants Analyzed	81	67
Median (Inter-Quartile Range) Unit of Measure: cells per mm3
	541 (398 to 702)	453 (379 to 580)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Interleukin-2 Group, Control Group
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.069
	Comments	Biphasic decline of CD4 after week 24 : first slope before W32 and weaker decline until W168.Slopes significantly different (all p values ≤0.0001) between the 2 groups, more pronounced in the IL-2 groups
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

3.Secondary Outcome


Title	AIDS Events
Description	AIDS defined events according to CDC classification
Description	AIDS defined events according to CDC classification
Time Frame	Overall study

Outcome Measure Data

Analysis Population Description

IL-2 arm : Oesophageal candidasis at W196
Control arm :Ocular B-cell lymphoma at W43,Oesophageal candidasis at W82, B-cell lymphoma at W104


Arm/Group Title	Interleukin-2 Group	Control Group
Arm/Group Description:	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Arm/Group Description:	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Overall Number of Participants Analyzed	81	67
Measure Type: Number Unit of Measure: event
	1	3

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Interleukin-2 Group	Control Group
Arm/Group Description	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
Arm/Group Description	HAART and tree cycles of IL-2	HAART alone (without Interleukin-2)
All-Cause Mortality
	Interleukin-2 Group	Control Group
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Interleukin-2 Group	Control Group
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Interleukin-2 Group	Control Group
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The sponsor can review results communications prior to public release and can embargo communications regarding trial results with no delay specified

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Pr G. Chene
Organization:	INSERM U897 Bordeaux FRANCE
Phone:	557571392 ext +33
EMail:	genevieve.chene@isped.u-bordeaux2.fr

Publications:

Arnó A, Ruiz L, Juan M, Jou A, Balagué M, Zayat MK, Marfil S, Martínez-Picado J, Martínez MA, Romeu J, Pujol-Borrell R, Lane C, Clotet B. Efficacy of low-dose subcutaneous interleukin-2 to treat advanced human immunodeficiency virus type 1 in persons with </=250/microL CD4 T cells and undetectable plasma virus load. J Infect Dis. 1999 Jul;180(1):56-60.

Carr A, Emery S, Lloyd A, Hoy J, Garsia R, French M, Stewart G, Fyfe G, Cooper DA. Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group. J Infect Dis. 1998 Oct;178(4):992-9.

Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet. 2000 Oct 21;356(9239):1423-30. Review.

Layout table for additonal information

Responsible Party:	Irini Sereti, M.D./National Institute of Allergy and Infectious Diseases, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00071890
Other Study ID Numbers:	040018 04-I-0018 ( Other Identifier: NIAID ) ANRS 118 ILIADE ( Other Identifier: ANRS )
First Submitted:	November 3, 2003
First Posted:	November 4, 2003
Results First Submitted:	September 13, 2010
Results First Posted:	October 5, 2010
Last Update Posted:	October 5, 2010

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