Trial Outcomes & Findings for An International Study to Evaluate Recombinant Interleukin-2 in HIV Positive Patients Taking Anti-retroviral Therapy (NCT NCT00004978)

Last Updated: 2021-11-05

Results Overview

Participants who die or experience at least one: any CDC Category C 1993 AIDS-defining events or one of the following: invasive aspergillosis, bartonellosis, Chagas disease, Herpes zoster, visceral Leishmaniasis, Hodgkin's lymphoma, non-Hodgkin's lymphoma (all cell types), microsporidiosis, nocardiosis, disseminated Penicillium marneffii, extrapulmonary Pneumocystis carinii, and Rhodococcus equi disease

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4150 participants

Primary outcome timeframe

from randomization through study end - median of 7.6 years follow-up

Results posted on

2021-11-05

Participant Flow

Patients were enrolled to ESPRIT between 2000 and 2003. As per the ESPRIT protocol, patients from previous Vanguard studies (in Thailand, Argentina, and the U.S., enrolled 1997-1999) were followed and included in the analysis cohort of this study if at least 90% of patients from that site consented to ESPRIT.

Participant milestones

Participant milestones
Measure	rIL-2 Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 Control group - no study-assigned medication
Overall Study STARTED	2090	2060
Overall Study COMPLETED	1846	1790
Overall Study NOT COMPLETED	244	270

Reasons for withdrawal

Reasons for withdrawal
Measure	rIL-2 Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 Control group - no study-assigned medication
Overall Study Death	107	116
Overall Study Lost to Follow-up	101	108
Overall Study Withdrawal by Subject	17	26
Overall Study site closure - not in analysis cohort	19	20

Baseline Characteristics

An International Study to Evaluate Recombinant Interleukin-2 in HIV Positive Patients Taking Anti-retroviral Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rIL-2 n=2090 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2060 Participants Control group - no study-assigned medication	Total n=4150 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2071 Participants n=5 Participants	2032 Participants n=7 Participants	4103 Participants n=5 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	28 Participants n=7 Participants	47 Participants n=5 Participants
Age, Continuous	40.8 years STANDARD_DEVIATION 8.8 • n=5 Participants	40.9 years STANDARD_DEVIATION 9.1 • n=7 Participants	40.8 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	388 Participants n=5 Participants	381 Participants n=7 Participants	769 Participants n=5 Participants
Sex: Female, Male Male	1702 Participants n=5 Participants	1679 Participants n=7 Participants	3381 Participants n=5 Participants
Region of Enrollment Argentina	276 participants n=5 Participants	278 participants n=7 Participants	554 participants n=5 Participants
Region of Enrollment Australia	107 participants n=5 Participants	98 participants n=7 Participants	205 participants n=5 Participants
Region of Enrollment Austria	16 participants n=5 Participants	18 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Belgium	39 participants n=5 Participants	41 participants n=7 Participants	80 participants n=5 Participants
Region of Enrollment Brazil	48 participants n=5 Participants	50 participants n=7 Participants	98 participants n=5 Participants
Region of Enrollment Canada	74 participants n=5 Participants	67 participants n=7 Participants	141 participants n=5 Participants
Region of Enrollment Denmark	39 participants n=5 Participants	33 participants n=7 Participants	72 participants n=5 Participants
Region of Enrollment France	86 participants n=5 Participants	96 participants n=7 Participants	182 participants n=5 Participants
Region of Enrollment Germany	136 participants n=5 Participants	130 participants n=7 Participants	266 participants n=5 Participants
Region of Enrollment Ireland	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Israel	31 participants n=5 Participants	33 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment Italy	50 participants n=5 Participants	54 participants n=7 Participants	104 participants n=5 Participants
Region of Enrollment Japan	14 participants n=5 Participants	11 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Morocco	12 participants n=5 Participants	14 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment Netherlands	29 participants n=5 Participants	25 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment Norway	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Poland	48 participants n=5 Participants	52 participants n=7 Participants	100 participants n=5 Participants
Region of Enrollment Portugal	51 participants n=5 Participants	56 participants n=7 Participants	107 participants n=5 Participants
Region of Enrollment Singapore	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment Spain	151 participants n=5 Participants	157 participants n=7 Participants	308 participants n=5 Participants
Region of Enrollment Sweden	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Switzerland	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Thailand	182 participants n=5 Participants	183 participants n=7 Participants	365 participants n=5 Participants
Region of Enrollment United Kingdom	165 participants n=5 Participants	163 participants n=7 Participants	328 participants n=5 Participants
Region of Enrollment United States	511 participants n=5 Participants	477 participants n=7 Participants	988 participants n=5 Participants
CD4+ cell count	465 cells/mm^3 n=5 Participants	451 cells/mm^3 n=7 Participants	458 cells/mm^3 n=5 Participants

PRIMARY outcome

Timeframe: from randomization through study end - median of 7.6 years follow-up

Population: ITT

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
New or Recurrent HIV Disease Progression Event Including Death	159 participants	165 participants

SECONDARY outcome

Timeframe: from randomization through study end - median of 7.6 years follow-up

Population: ITT

Patients with at least one: progressive multifocal leukoencephalopathy, lymphoma, visceral Kaposi's sarcoma, AIDS dementia complex, toxoplasmosis, histoplasmosis, cryptococcosis, Mycobacterium avium complex, wasting syndrome, and cytomegalovirus disease.

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
New or Recurrent Serious HIV Disease Progression Event Including Death	126 participants	130 participants

SECONDARY outcome

Timeframe: from randomization through study end - median of 7.6 years follow-up

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
Number of Participants Who Died From Any Cause	107 participants	116 participants

SECONDARY outcome

Timeframe: from randomization through 15 November 2008 - median of 7.6 years follow-up

Includes first new episode of: CDC Category C 1993 AIDS-defining events plus invasive aspergillosis, bartonellosis, Chagas disease, Herpes zoster, visceral Leishmaniasis, Hodgkin's lymphoma, non-Hodgkin's lymphoma (all cell types), microsporidiosis, nocardiosis, disseminated Penicillium marneffii, extrapulmonary Pneumocystis carinii, and Rhodococcus equi disease

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
Participants With a New Disease Progression Event or Death	154 participants	164 participants

SECONDARY outcome

Timeframe: from randomization through study end - median of 7.6 years follow-up

Population: CD4+ cell counts averaged over all participants with at least one CD4+ measurement recorded during follow-up.

Average of all available CD4+ cell counts measured at follow-up visits

Outcome measures

Outcome measures
Measure	rIL-2 n=2053 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2024 Participants Control group - no study-assigned medication
Absolute CD4 Cell Counts Averaged Throughout Followup	715.4 cells/mm^3 Standard Deviation 273.1	556.3 cells/mm^3 Standard Deviation 193.0

SECONDARY outcome

Timeframe: From randomization through study end - median of 7.6 years follow-up

Population: HIV-RNA measurement averaged over followup visits for all participants with at least one follow-up measurement.

log10 HIV-RNA averaged throughout follow-up

Outcome measures

Outcome measures
Measure	rIL-2 n=2065 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2036 Participants Control group - no study-assigned medication
Plasma HIV RNA Levels	2.20 log10 HIV-RNA Standard Deviation 0.65	2.17 log10 HIV-RNA Standard Deviation 0.61

SECONDARY outcome

Timeframe: From randomization through study end - median of 7.6 years follow-up

Number of participants who changed ART at least once during the study period.

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
Number of Participants With Changes in Anti-retroviral Treatment (ART)	1760 participants	1751 participants

SECONDARY outcome

Timeframe: From randomization through study end - median of 7.6 years follow-up

Participants with at least one grade 4 sign or symptom (except those limited to a laboratory measurement), other than AIDS-defining conditions. Events were graded according to a standardized toxicity table. Events not specifically contained in the toxicity table were considered Grade 4 if they resulted in extreme limitation in activity or required significant medical intervention/therapy, hospitalization or hospice care. Grade 4 events by type are given under the adverse events section.

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
Grade 4 Signs and Symptoms	466 Participants	383 Participants

SECONDARY outcome

Timeframe: last followup visit - median of 7.6 years follow-up

Population: Intention to treat (ITT) - Medication use recorded on the last followup visit attended among all participants attending at least one followup visit.

Number of participants using pneumocystis pneumonia (PCP) prophylaxis at the last attended followup visit.

Outcome measures

Outcome measures
Measure	rIL-2 n=2028 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2005 Participants Control group - no study-assigned medication
Pattern of Use of Prophylaxis for Opportunistic Infections	54 participants	53 participants

SECONDARY outcome

Timeframe: From randomization through study end - median of 7.6 years follow-up

Number of participants experiencing a "serious non-AIDS" event defined as first serious cardiovascular, renal, or hepatic event, or non-AIDS malignancy.

Outcome measures

Outcome measures
Measure	rIL-2 n=2071 Participants Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 Participants Control group - no study-assigned medication
Hepatic, Metabolic, and Cardiac Conditions	134 participants	136 participants

Adverse Events

rIL-2

Serious events: 466 serious events

Other events: 133 other events

Deaths: 0 deaths

No rIL-2

Serious events: 383 serious events

Other events: 92 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	rIL-2 n=2071 participants at risk Subcutaneous recombinant interleukin-2 (rIL-2) therapy	No rIL-2 n=2040 participants at risk Control group - no study-assigned medication
Cardiac disorders Acute myocardial infarction	0.77% 16/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.74% 15/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Blood and lymphatic system disorders Anaemia	0.43% 9/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.49% 10/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Infections and infestations Appendicitis	0.48% 10/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.39% 8/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Nervous system disorders Cerebrovascular accident	0.58% 12/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.20% 4/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Cardiac disorders Coronary artery disease	0.58% 12/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.44% 9/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Vascular disorders Deep vein thrombosis	0.48% 10/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.10% 2/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Psychiatric disorders Depression	0.68% 14/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.34% 7/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Gastrointestinal disorders Diarrhoea	0.77% 16/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.49% 10/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Cardiac disorders Myocardial infarction	0.68% 14/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.88% 18/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
General disorders Pyrexia	0.87% 18/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.44% 9/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Psychiatric disorders Suicide attempt	0.53% 11/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.49% 10/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.
Gastrointestinal disorders Vomiting	0.63% 13/2071 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.	0.15% 3/2040 • Grade 4 events were reportable from randomization through study end (15 November 2008), irrespective of whether patient was taking a study treatment. Adverse events are grade 4 events (excluding AIDS-defining events and events limited to abnormal laboratory values), reportable in both treatment arms. All grade 4 events are included under "serious adverse events", categorized according to MedDRA HLGT. Common adverse events of any grade are reported under "other adverse events" by MedDRA PT.

Additional Information

James Neaton, PhD

Division of Biostatistics, University of Minnesota

Phone: 612-626-9040

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place