Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People (STALWART)

This study has been completed.
Sponsor:
Collaborator:
Chiron Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00110812
First received: May 13, 2005
Last updated: April 7, 2014
Last verified: April 2014
Results First Received: December 12, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Intervention: Drug: IL-2

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled by HIV care providers between December 2005 and June 2008. When the main study ended in February 2009, patients who consented to a study extension were followed another 2 years, during which study drug was not given.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART during the main study or extension
IL-2 Without ART During the main study, participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Patients did not receive aldesleukin during the extension phase.
IL-2 With Pericycle HAART During the main study, participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). Patients did not receive aldesleukin during the extension phase.

Participant Flow for 2 periods

Period 1:   Main Study
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
STARTED     91     89     87  
COMPLETED     83     78     74  
NOT COMPLETED     8     11     13  
Death                 0                 0                 2  
Withdrawal by Subject                 0                 0                 1  
Lost to Follow-up                 8                 11                 10  

Period 2:   Extended Follow-up
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
STARTED     80     69     73  
COMPLETED     78     65     69  
NOT COMPLETED     2     4     4  
Death                 1                 0                 3  
Withdrawal by Subject                 0                 1                 0  
Lost to Follow-up                 1                 3                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).
Total Total of all reporting groups

Baseline Measures
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART     Total  
Number of Participants  
[units: participants]
  91     89     87     267  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     91     89     85     265  
>=65 years     0     0     2     2  
Age  
[units: years]
Mean ± Standard Deviation
  37.1  ± 7.7     37.3  ± 9.6     37.8  ± 11.0     37.4  ± 9.5  
Gender  
[units: participants]
       
Female     16     17     13     46  
Male     75     72     74     221  
Region of Enrollment  
[units: participants]
       
Portugal     3     3     4     10  
United States     8     9     9     26  
Morocco     1     0     0     1  
Argentina     25     24     21     70  
Thailand     21     21     22     64  
Spain     1     1     1     3  
Poland     3     2     3     8  
Australia     10     8     8     26  
Chile     2     5     4     11  
United Kingdom     8     9     10     27  
Italy     9     7     5     21  
CD4 cell count  
[units: cells/mm^3]
Median ( Inter-Quartile Range )
  432  
  ( 375 to 507 )  
  398  
  ( 355 to 458 )  
  425  
  ( 365 to 535 )  
  418  
  ( 359 to 511 )  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Mean Change in CD4+ T Lymphocyte Count   [ Time Frame: Week 32 ]

Measure Type Primary
Measure Title Mean Change in CD4+ T Lymphocyte Count
Measure Description Change in CD4 count from baseline to week 32.
Time Frame Week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
patients for whom the week-32 CD4+ cell count was measured

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  83     78     74  
Mean Change in CD4+ T Lymphocyte Count  
[units: cell/mm^3]
Mean ± Standard Deviation
  -21.8  ± 93.1     113.7  ± 216.8     110.4  ± 174.7  


Statistical Analysis 1 for Mean Change in CD4+ T Lymphocyte Count
Groups [1] No IL-2 vs. IL-2 Without ART
Method [2] ANOVA
P Value [3] <.001
Mean Difference (Net) [4] 134
95% Confidence Interval ( 70 to 198 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified by geographic region and adjusted for baseline CD4.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for 3 pairwise comparisons.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Mean Change in CD4+ T Lymphocyte Count
Groups [1] No IL-2 vs. IL-2 With Pericycle HAART
Method [2] ANOVA
P Value [3] <.001
Mean Difference (Net) [4] 133
95% Confidence Interval ( 68 to 199 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified by geographic region and adjusted for baseline CD4.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for 3 pairwise comparisons.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Discontinuation of IL-2   [ Time Frame: week 32 ]

Measure Type Secondary
Measure Title Discontinuation of IL-2
Measure Description Patients receiving fewer than 3 cycles of IL-2 by week 32
Time Frame week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all patients randomized to a study arm containing IL-2

Reporting Groups
  Description
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  89     87  
Discontinuation of IL-2  
[units: participants]
  12     32  

No statistical analysis provided for Discontinuation of IL-2



3.  Secondary:   Plasma HIV RNA   [ Time Frame: At Week 32 ]

Measure Type Secondary
Measure Title Plasma HIV RNA
Measure Description change from baseline in HIV-RNA copies/ml (log10)
Time Frame At Week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients for whom HIV-RNA was available at week 32

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  82     79     72  
Plasma HIV RNA  
[units: copies/ml (log 10)]
Mean ± Standard Deviation
  -.39  ± 1.03     -.07  ± .80     -.01  ± .40  


Statistical Analysis 1 for Plasma HIV RNA
Groups [1] No IL-2 vs. IL-2 Without ART
Method [2] ANOVA
P Value [3] .01
Mean Difference (Net) [4] .31
95% Confidence Interval ( .08 to .54 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified by region and adjusted for baseline HIV-RNA.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Plasma HIV RNA
Groups [1] No IL-2 vs. IL-2 With Pericycle HAART
Method [2] ANOVA
P Value [3] .003
Mean Difference (Net) [4] .36
95% Confidence Interval ( .12 to .60 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified by region and adjusted for baseline HIV-RNA.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Change in CD4 T Lymphocyte Count   [ Time Frame: At Month 12 ]

Measure Type Secondary
Measure Title Change in CD4 T Lymphocyte Count
Measure Description change from baseline to month 12 in CD4 T lymphocyte count
Time Frame At Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
patients for whom the month 12 CD4 count was available

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  78     77     72  
Change in CD4 T Lymphocyte Count  
[units: cell/mm^3]
Mean ± Standard Deviation
  -8.4  ± 129.1     59.0  ± 176.0     49.8  ± 155.6  


Statistical Analysis 1 for Change in CD4 T Lymphocyte Count
Groups [1] No IL-2 vs. IL-2 Without ART
Method [2] ANOVA
P Value [3] .009
Mean Difference (Net) [4] 65.8
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  ANOVA with stratification by region and adjustment for baseline CD4
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in CD4 T Lymphocyte Count
Groups [1] No IL-2 vs. IL-2 With Pericycle HAART
Method [2] ANOVA
P Value [3] .02
Mean Difference (Net) [4] 58.2
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  stratified by region and adjusted for baseline CD4
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   HIV-1 Genotype Changes   [ Time Frame: after 3rd cycle of IL-2 ]

Measure Type Secondary
Measure Title HIV-1 Genotype Changes
Measure Description Patients who developed mutations associated with antiretroviral drugs.
Time Frame after 3rd cycle of IL-2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol, the analysis of genotypic changes associated with antiretroviral resistance was restricted patients in one arm, namely, patients assigned to take pericycle HAART who completed 3 cycles of IL-2 and who had successful genotypes.

Reporting Groups
  Description
IL-2 With Pericycle HAART No text entered.

Measured Values
    IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  47  
HIV-1 Genotype Changes  
[units: participants]
  2  

No statistical analysis provided for HIV-1 Genotype Changes



6.  Secondary:   Fasting Lipid Profile   [ Time Frame: week 32 ]

Measure Type Secondary
Measure Title Fasting Lipid Profile
Measure Description total fasting cholesterol
Time Frame week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all patients with laboratory data at week 32 who reported fasting

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  65     66     58  
Fasting Lipid Profile  
[units: mg/dl]
Mean ± Standard Deviation
  173.4  ± 33.7     167.0  ± 32.7     164.6  ± 40.8  

No statistical analysis provided for Fasting Lipid Profile



7.  Secondary:   Disease Progression or Death   [ Time Frame: throughout study, through Feb 28 2009 (median followup of 19 months) ]

Measure Type Secondary
Measure Title Disease Progression or Death
Measure Description occurrence of an opportunistic event (AIDS-defining infection or malignancy) or death
Time Frame throughout study, through Feb 28 2009 (median followup of 19 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all randomized patients

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  91     89     87  
Disease Progression or Death  
[units: participants]
  1     5     7  


Statistical Analysis 1 for Disease Progression or Death
Groups [1] No IL-2 vs. IL-2 Without ART
Method [2] Regression, Cox
P Value [3] .14
Hazard Ratio (HR) [4] 5.08
95% Confidence Interval ( 0.59 to 43.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Unadjusted, stratified by region.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Patients taking IL-2 alone compared to patients not taking IL-2.

Statistical Analysis 2 for Disease Progression or Death
Groups [1] No IL-2 vs. IL-2 With Pericycle HAART
Method [2] Regression, Cox
P Value [3] .08
Hazard Ratio (HR) [4] 6.56
95% Confidence Interval ( 0.80 to 53.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Unadjusted, stratified by region.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Patients taking IL-2 plus pericycle HAART compared to patients not receiving IL-2



8.  Secondary:   Initiation of Continuous ART   [ Time Frame: from randomization through February 28, 2009 ]

Measure Type Secondary
Measure Title Initiation of Continuous ART
Measure Description While patients were not taking ART at baseline or while undergoing IL-2 cycles (other than use of pericycle ART in one of the three groups), some chose to start an ART regimen during the study.
Time Frame from randomization through February 28, 2009  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all patients randomized

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  91     89     87  
Initiation of Continuous ART  
[units: participants]
  34     23     14  


Statistical Analysis 1 for Initiation of Continuous ART
Groups [1] No IL-2 vs. IL-2 Without ART
Method [2] Regression, Cox
P Value [3] .048
Hazard Ratio (HR) [4] .58
95% Confidence Interval ( .34 to .99 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  IL-2 without ART vs control group

Statistical Analysis 2 for Initiation of Continuous ART
Groups [1] No IL-2 vs. IL-2 With Pericycle HAART
Method [2] Regression, Cox
P Value [3] <.001
Hazard Ratio (HR) [4] .32
95% Confidence Interval ( .17 to .62 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  IL-2 with pericycle HAART compared to control



9.  Secondary:   Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12   [ Time Frame: month 12 ]

Measure Type Secondary
Measure Title Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12
Measure Description No text entered.
Time Frame month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
patients for whom HIV-RNA measurement was available at baseline and month 12.

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  77     74     71  
Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12  
[units: copies/ml (log 10)]
Mean ± Standard Deviation
  -0.64  ± 1.24     -0.28  ± 0.95     -0.09  ± 0.84  


Statistical Analysis 1 for Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12
Groups [1] No IL-2 vs. IL-2 Without ART
Method [2] ANOVA
P Value [3] .03
Mean Difference (Net) [4] 0.34
95% Confidence Interval ( 0.03 to 0.64 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by region and adjusted for baseline HIV-RNA
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in HIV-RNA Copies/ml (log10) From Baseline to Month 12
Groups [1] No IL-2 vs. IL-2 With Pericycle HAART
Method [2] ANOVA
P Value [3] <.001
Mean Difference (Net) [4] 0.54
95% Confidence Interval ( 0.24 to 0.85 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by region and adjusted for baseline HIV-RNA
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



10.  Secondary:   Thyroid Stimulating Hormone   [ Time Frame: week 32 ]

Measure Type Secondary
Measure Title Thyroid Stimulating Hormone
Measure Description Number of participants with thyroid stimulating hormone greater than the upper limit of normal
Time Frame week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all patients with TSH measured at 32 weeks

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  79     75     71  
Thyroid Stimulating Hormone  
[units: participants]
  3     2     7  

No statistical analysis provided for Thyroid Stimulating Hormone



11.  Secondary:   SGOT   [ Time Frame: week 32 ]

Measure Type Secondary
Measure Title SGOT
Measure Description Number of participants with aspartate aminotransferase (SGOT) greater than 5 times the upper limit of normal
Time Frame week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
all patients with SGOT measured at week 32

Reporting Groups
  Description
No IL-2 Participants will receive no aldesleukin or HAART
IL-2 Without ART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level.
IL-2 With Pericycle HAART Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; in addition, this group will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle).

Measured Values
    No IL-2     IL-2 Without ART     IL-2 With Pericycle HAART  
Number of Participants Analyzed  
[units: participants]
  83     79     74  
SGOT  
[units: participants]
  1     0     0  

No statistical analysis provided for SGOT



12.  Post-Hoc:   Opportunistic Disease or Death During the Trial Extension Phase   [ Time Frame: two years following close of main study ]

Measure Type Post-Hoc
Measure Title Opportunistic Disease or Death During the Trial Extension Phase
Measure Description Incidence of an opportunistic event (AIDS-defining infection or malignancy) or death between February 28, 2009, when the main study ended, and February 28, 2011, when the extended phase was completed.
Time Frame two years following close of main study  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who were alive at the end of the main study and who consented to be followed for an additional 2 years in the extension phase. Because the focus of the extension was on the safety of patients exposed to IL-2, the outcomes were summarized for the two groups exposed to IL-2 vs. the group that did not take IL-2.

Reporting Groups
  Description
IL-2 Consenting patients who were assigned IL-2 during the main phase of the study, including patients who took IL-2 alone as well as patients who took IL-2 with ART.
Control Consenting patients who were in the control group during the main phase of the trial.

Measured Values
    IL-2     Control  
Number of Participants Analyzed  
[units: participants]
  142     80  
Opportunistic Disease or Death During the Trial Extension Phase  
[units: participants]
  8     3  


Statistical Analysis 1 for Opportunistic Disease or Death During the Trial Extension Phase
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] .59
Hazard Ratio (HR) [4] 1.45
95% Confidence Interval ( 0.38 to 5.45 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratification by region.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  IL-2 group compared to control group



13.  Post-Hoc:   CD4+ Cell Count 2 Years Post-study   [ Time Frame: two years following close of main study ]

Measure Type Post-Hoc
Measure Title CD4+ Cell Count 2 Years Post-study
Measure Description No text entered.
Time Frame two years following close of main study  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients for whom a CD4 count measurement was available during the extension phase. Because the focus of the extension was on the safety of patients exposed to IL-2, the outcomes were summarized for the two groups exposed to IL-2 vs. the group that did not take IL-2.

Reporting Groups
  Description
IL-2 Consenting patients who were assigned IL-2 during the main phase of the study, including patients who took IL-2 alone as well as patients who took IL-2 with ART.
Control Consenting patients who were in the control group during the main phase of the trial.

Measured Values
    IL-2     Control  
Number of Participants Analyzed  
[units: participants]
  141     80  
CD4+ Cell Count 2 Years Post-study  
[units: cell/mm^3]
Mean ± Standard Deviation
  499.9  ± 191.4     557.2  ± 225.5  


Statistical Analysis 1 for CD4+ Cell Count 2 Years Post-study
Groups [1] All groups
Method [2] ANOVA
P Value [3] .05
Mean Difference (Final Values) [4] -55.9
Standard Error of the mean ± 28.4
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Last measured CD4 is imputed if month 24 CD4 count is missing. Analysis is adjusted for baseline CD4.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  IL-2 group minus control group CD4.



14.  Post-Hoc:   Undetectable HIV-RNA   [ Time Frame: 24 months post-trial ]

Measure Type Post-Hoc
Measure Title Undetectable HIV-RNA
Measure Description Patients with undetectable HIV-RNA levels measured at 24 months after the close of the main study, at the end of the extension phase.
Time Frame 24 months post-trial  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients for whom an HIV-RNA measurement was available during the extension phase. Because the focus of the extension was on the safety of patients exposed to IL-2, the outcomes were summarized for the two groups exposed to IL-2 vs. the group that did not take IL-2.

Reporting Groups
  Description
IL-2 Consenting patients who were assigned IL-2 during the main phase of the study, including patients who took IL-2 alone as well as patients who took IL-2 with ART.
Control Consenting patients who were in the control group during the main phase of the trial.

Measured Values
    IL-2     Control  
Number of Participants Analyzed  
[units: participants]
  141     80  
Undetectable HIV-RNA  
[units: participants]
  97     60  

No statistical analysis provided for Undetectable HIV-RNA



15.  Post-Hoc:   Commencement of Continuous Antiretroviral Treatment   [ Time Frame: from randomization through February 28, 2011, the end of the extension phase ]

Measure Type Post-Hoc
Measure Title Commencement of Continuous Antiretroviral Treatment
Measure Description Number of patients commencing continuous antiretroviral treatment.
Time Frame from randomization through February 28, 2011, the end of the extension phase  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients are counted. Patients who did not consent to the extension phase are censored at the end of the main study (Feb 28, 2009). Because the focus of the extension was on the safety of patients exposed to IL-2, the outcomes were summarized for the two groups exposed to IL-2 vs. the group that did not take IL-2.

Reporting Groups
  Description
IL-2 Consenting patients who were assigned IL-2 during the main phase of the study, including patients who took IL-2 alone as well as patients who took IL-2 with ART.
Control Consenting patients who were in the control group during the main phase of the trial.

Measured Values
    IL-2     Control  
Number of Participants Analyzed  
[units: participants]
  176     91  
Commencement of Continuous Antiretroviral Treatment  
[units: participants]
  108     66  


Statistical Analysis 1 for Commencement of Continuous Antiretroviral Treatment
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] .03
Hazard Ratio (HR) [4] .71
95% Confidence Interval ( .52 to .97 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  IL-2 groups vs. control




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
All randomized patients were followed through 28 Feb 2009. A subset of 222 consenting patients were followed 2 additional years, through 28 Feb 2011.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Deborah Wentworth
Organization: University of Minnesota
phone: 612-726-9005
e-mail: wentw001@umn.edu


Publications:
Publications automatically indexed to this study:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00110812     History of Changes
Obsolete Identifiers: NCT00106730
Other Study ID Numbers: ESPRIT 002, 10053
Study First Received: May 13, 2005
Results First Received: December 12, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration