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: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 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 (NCT00071890), a randomized phase 2 study. The primary outcome is Proportion of Patients Without Failure of Strategy From Week 0 to Week 72.

2. Clinical Question

The question concerns a treatment strategy over time, not simply whether IL-2 changes a CD4 count at one visit. The study summary frames the strategy around interrupting antiretroviral treatment while seeking to preserve CD4 counts and extend the period without treatment. The primary outcome combines several reasons the planned strategy could fail, so its result reflects the composite definition as well as the assigned group.

The registry also lists changes in CD4 counts at week 72 and AIDS events as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. The posted primary result therefore addresses the defined strategy-failure outcome, rather than providing a complete account of every clinical outcome considered by the study.

3. Trial Design

The registry describes a randomized, parallel-group study with no masking. It classifies the trial as Phase 2, while the study title describes it as Phase II/III. The registry lists enrollment of 148. The intervention group received HAART and three cycles of IL-2; the control group received HAART alone. The registry record does not report the allocation ratio or further details of the randomization procedure.

The study’s central strategy involved a planned interruption of antiretroviral therapy at week 24. The primary outcome covered week 0 through week 72, a period that includes both the time before the planned interruption and the subsequent period. Restarting antiretroviral treatment between week 24 and week 72 for any reason counted as a strategy failure. A participant also met the failure definition if the planned interruption at week 24 could not be done for any reason.

The primary analysis is described as intent to treat, with missing outcomes counted as failure. This approach classifies participants according to the analysis population stated in the registry and treats missing status as an unfavorable outcome for the composite. The record does not report the number of missing outcomes or how many failures arose from each component.

The registry lists changes in CD4 counts at week 72 and AIDS events as secondary outcomes, but their numerical results are not reported in the registry record. The record identifies two reported analyses, including a chi-squared analysis comparing the primary outcome groups. It does not report a detailed statistical analysis plan, the procedures used to generate the random sequence, or whether any interim analyses took place.

The intervention descriptions and primary outcome definition indicate that the comparison is between two assigned strategies, rather than between IL-2 and no treatment in isolation: the control group received HAART, and interruption was part of the study strategy. Because the study was unmasked, participants and study personnel were not blinded according to the registry’s masking classification. The registry record does not report how that design feature was handled in outcome assessment.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 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)

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to treat analysis, missing = failure.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients Without Failure of Strategy From Week 0 to Week 72, measured over week 72.

The primary endpoint is the proportion of patients without failure of strategy from week 0 to week 72. It is reported as a percentage with a 95% confidence interval for each group. A participant was classified as having a failure at the first occurrence of any listed event: a CD4 T-lymphocyte count below 350 cells/mm3, confirmed by a second measurement after 2-4 weeks; inability to carry out the planned interruption at week 24; restarting antiretroviral treatment between week 24 and week 72; clinical progression to a stage C AIDS diagnosis; death from any cause during the period; or loss to follow-up.

This composite endpoint reflects whether the planned treatment strategy could be followed without any of its specified failure events. It includes laboratory, treatment, clinical, and follow-up events, which are not interchangeable in meaning. A lower proportion without failure can therefore arise through different routes, and the registry does not report the number of events attributable to each component.

Using a composite can summarize several outcomes relevant to the strategy in one measure. It also means the overall result should be interpreted in light of the components and their definitions. In this record, missing outcomes are counted as failure in the intent-to-treat analysis. That rule makes the handling of missing status part of the endpoint calculation, rather than a separate exclusion from the analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the percentage represent?

For each group, the percentage describes the share classified as remaining free of the defined strategy-failure events over the stated period. This is a binary outcome at the level of each participant: the status is either without a recorded failure under the definition or a failure. The registry reports the group summaries as percentages and gives a confidence interval for each one.

What does a confidence interval communicate?

In general, a confidence interval conveys the statistical uncertainty around an estimate using a method with a stated coverage level. A narrower interval indicates greater precision under that method; a wider interval indicates more uncertainty. The reported intervals are 95% confidence intervals: 63% to 83% for the Interleukin-2 group and 43% to 67% for the Control group. They are intervals for each group’s proportion, not a confidence interval for the difference between groups. A comparative interval is not reported in the registry record.

What does the chi-squared test assess?

A chi-squared test is a general method for assessing whether observed counts across categories are compatible with an assumption of no association or no difference, depending on the comparison being made. For this trial, the registry identifies a chi-squared analysis of the two groups and reports p = 0.025. The p-value expresses how unusual data at least as discrepant as those observed would be under the test’s null model and assumptions. It is not an effect-size measure, and it does not establish that the endpoint’s composite components behaved alike.

The registry does not report the contingency counts used in the test, the exact test specification, or a detailed statistical analysis plan. The listed group sizes are 81 in the Interleukin-2 group and 67 in the Control group; the group results are 73% and 55%, respectively. No additional test statistic or comparative effect estimate is reported. A simple recalculation from posted summary statistics is not reported as an estimable two-arm comparison for this count-other endpoint. The sponsor’s reported analysis is therefore the relevant inferential result in the registry record.

Why does the composite definition matter?

Composite outcomes combine several distinct events into a single endpoint. In general, this can capture a broader view of whether a strategy met its goals, but the overall result may be influenced by components that differ in severity, frequency, and interpretation. Here, failure could reflect a CD4 count below the threshold with confirmation, inability to interrupt therapy as planned, restarting treatment, clinical progression to stage C AIDS, death, or loss to follow-up. Because component-specific results are not reported in the registry record, the overall percentage cannot show which event types chiefly account for the group results.

Why does missing-as-failure handling matter?

The record defines the primary population as intent to treat and states that missing outcomes count as failure. In general, assigning missing status to an outcome category makes the analysis depend on that rule. It avoids treating missing participants as if they had an observed successful outcome, but it also means that loss to follow-up is explicitly part of the failure definition and that missingness can affect the group proportions. The record does not report the number of missing outcomes or separate losses to follow-up from other failure components.

What can randomization and lack of masking contribute?

In general, random assignment is intended to make the groups comparable at the start of a trial with respect to both measured and unmeasured factors, apart from chance variation. It supports interpreting the group comparison as a comparison of assigned strategies. It does not guarantee that every factor is balanced or remove uncertainty. The trial is classified as randomized and unmasked. In general, lack of masking may matter when decisions, behavior, or outcome assessment can be influenced by knowledge of assignment. The registry does not report details about outcome assessment procedures or safeguards.

What is the role of planning illustrations?

Sample-size illustrations based on an observed effect are planning exercises, not measurements of how much power the completed trial achieved. In general, such calculations depend on assumptions about the effect to detect, significance level, allocation, and statistical method. The registry record does not report the trial’s original sample-size justification, so an observed-effect planning illustration should not be read as evidence about the original design rationale or as observed power.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a chi-squared analysis, with p = 0.025. It gives the group-level proportions without strategy failure as 73% for the Interleukin-2 group and 55% for the Control group, along with their respective 95% confidence intervals. No recalculated two-arm comparison is reported as estimable from the posted summary statistics for this count-other endpoint.

The reported chi-squared result is therefore the inferential comparison available in the registry record. The group percentages and their confidence intervals describe the outcomes by group, while the p-value comes from the sponsor’s analysis. These quantities answer related but different questions: the percentages summarize each group, the intervals convey uncertainty around those summaries, and the test evaluates the reported group comparison under its statistical assumptions.

The registry does not provide the detailed analysis specification or underlying contingency counts needed to reproduce the test from the record. It also does not report an adjusted comparative estimate. There is no discrepancy between a posted recalculation and the sponsor’s result identified in the registry record. The result should be read as the reported chi-squared comparison, not as an independently recalculated effect estimate.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and two secondary outcomes: changes in CD4 counts at week 72 and AIDS events. Numerical results for the secondary outcomes are not reported in the registry record. The record does not report whether the analysis plan specified a hierarchy among outcomes, a multiplicity adjustment, or how conclusions across multiple tests were to be controlled. The reported p-value is for the primary comparison and should not be taken as a summary of all outcomes considered by the study.

Multiplicity arises in general when several hypotheses are tested. Testing more outcomes can increase the chance that at least one result appears unusual under its null hypothesis, unless a plan accounts for the set of tests. Without details of the planned testing strategy, the registry’s p = 0.025 can be interpreted as the reported result for the primary comparison, but its role within a broader testing framework is not reported in the registry record.

For the primary outcome, the population is described as intent to treat, with missing outcomes counted as failure. Loss to follow-up is also listed as one of the failure events. Thus missingness is incorporated into the endpoint rule rather than handled solely through a separate complete-case analysis. The registry does not report how many outcomes were missing, how many participants were lost to follow-up, or how many failures arose from each reason. It also does not describe sensitivity analyses for alternative assumptions about missing outcomes.

The record does not report a detailed statistical analysis plan, the original sample-size justification, or whether interim analyses occurred. These omissions limit assessment of how the posted analysis relates to prespecified methods and whether any multiplicity considerations applied beyond the reported primary test. They do not alter the stated endpoint definition or the group results, but they constrain interpretation of the full analysis strategy.

12. What the Result Does, and Does Not, Mean

The posted result describes a higher reported proportion without strategy failure in the Interleukin-2 group than in the Control group during the week 0 to week 72 period. The registry reports 73% (95% confidence interval 63% to 83%) and 55% (95% confidence interval 43% to 67%), respectively, with a chi-squared p-value of 0.025. Those figures apply to the defined composite and the registry’s intent-to-treat rule that missing outcomes count as failure.

Statistically, the reported test indicates evidence of a difference between the group proportions under the chi-squared analysis. The confidence intervals show uncertainty in the separate group estimates; they do not by themselves give a direct interval estimate for the between-group effect. The record does not report an adjusted comparative estimate or a comparative confidence interval. The p-value does not measure the magnitude or practical importance of the difference.

The result does not identify which component of strategy failure explains the group pattern. A confirmed CD4 count below 350 cells/mm3, inability to proceed with interruption, treatment restart, clinical progression, death, and loss to follow-up all contribute to the endpoint, but component counts are not reported in the registry record. Nor does the primary result establish the findings for changes in CD4 counts at week 72 or AIDS events; numerical results for those secondary outcomes are not reported.

The outcome is limited to the stated period through week 72 and to the study’s specific strategy. It should not be interpreted as a result for periods beyond that window or as a comparison of IL-2 in isolation from HAART and the planned interruption strategy. The randomized design provides a basis for comparing assigned groups, while the unmasked design and the absence of further reporting about outcome assessment leave some aspects of measurement and decision-making unclear.

These findings are a statistical description of the posted trial results, not medical advice. They do not establish the benefit or harm of a treatment for an individual, and they do not replace consideration of the outcome definitions, the uncertainty around the estimates, or the limits of the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome evaluates a treatment strategy through a composite endpoint rather than a single biological measurement. The endpoint combines CD4 status, ability to carry out the planned interruption, treatment restart, clinical progression, death, and loss to follow-up. That structure makes the result relevant to whether the strategy remained free of defined failures, while also making component-level interpretation important.

The outcome’s rules determine what the reported percentages mean. A CD4 threshold event required confirmation by a second measurement after 2-4 weeks, and missing outcomes were counted as failure in the intent-to-treat analysis. These choices affect classification and are part of the statistical definition, not incidental details. The registry does not provide the numbers of failures by component or the extent of missingness, so readers cannot assess how much each rule contributed to the overall result.

The record also illustrates the distinction between group summaries and a test of comparison. The percentages and their confidence intervals describe each group; the chi-squared p-value provides the reported inferential comparison. The p-value does not convey the size or clinical importance of the group difference, and the registry does not report a comparative effect estimate with its own confidence interval.

Finally, the randomized, unmasked parallel-group design and the missing details in the registry record shape the limits of interpretation. Randomization supports comparison of assigned strategies, while the record does not describe allocation procedures, outcome assessment, or a full analysis plan. These features make it important to distinguish the reported primary result from unreported secondary results and from questions the registry cannot resolve.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record provides limited detail about how participants were randomized. It does not report the sequence-generation method, allocation concealment, or allocation ratio. Although the trial is classified as randomized, these details are not available for assessing the conduct of assignment from the record.

The study was unmasked. The registry does not describe whether outcome assessors were masked or how decisions about interrupting or restarting therapy were made. This matters because several components depend on clinical or treatment decisions, though the record does not establish whether the design affected those decisions. No inference about the direction or size of any such effect can be made from the posted information.

The primary outcome is a composite, but the record reports only the overall group proportions and not event counts for its individual components. The same overall result could reflect different mixes of CD4 threshold events, inability to interrupt, treatment restart, clinical progression, death, and loss to follow-up. Without component-specific results, those possibilities cannot be separated. The number of missing outcomes is also not reported, despite missing outcomes being counted as failure and loss to follow-up being included in the definition.

The registry reports no numerical results for the listed secondary outcomes, changes in CD4 counts at week 72 and AIDS events. It does not report an adjusted comparative estimate, a comparative confidence interval, a detailed statistical analysis plan, the original sample-size justification, or whether interim analyses occurred. These omissions restrict evaluation of the analysis strategy and the breadth of results. The trial’s listed enrollment and posted group results do not resolve those reporting gaps.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: 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 — NCT00071890.
• Registry record last updated 2010-10-05; status last verified 2010-09.
• Results first posted 2010-10-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a randomized, unmasked, parallel-group Phase 2 study of IL-2 plus HAART compared with HAART alone in people with HIV infection, a CD4 T-lymphocyte count greater than 500 cells/mm3, and prior antiretroviral treatment. The record lists enrollment of 148 and describes a planned treatment interruption at week 24.

The primary endpoint was the proportion without strategy failure from week 0 to week 72, with missing outcomes counted as failure in the intent-to-treat analysis. The reported proportions were 73% in the Interleukin-2 group and 55% in the Control group; the reported chi-squared comparison had p = 0.025. Secondary outcomes listed were changes in CD4 counts at week 72 and AIDS events, but their numerical results are not reported in the registry record.

The record lists the study as completed, with a start date of 2003-10 and primary completion in 2007-12. It does not report component-specific primary outcome results or a detailed statistical analysis plan.