Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r) (NCT00491556), a randomized na study. The primary outcome is Difference in CD4+ T Cell Percentage Between Week 0 and Week 48.

2. Clinical Question

The clinical question concerns immune-cell measurements during HAART management, rather than a clinical event endpoint. The study summary says the strategy was to evaluate a pre-DHHS guideline of HAART initiation followed by de-intensification in adolescents with mild immunosuppression. It describes comparing CD4% changes from baseline to Week 48 and then during de-intensification.

The registry record identifies random allocation to an experimental arm or standard care, but it does not give a numerical estimate of the primary endpoint, its uncertainty, or a test of a between-arm difference. Consequently, the stated clinical question can be described from the endpoint definition, but its answer cannot be recovered from the reported primary-outcome information. The eligibility criteria beyond the wording in the official title, and the operational definitions of mild immunosuppression and viral suppression, are not reported in the registry record.

3. Trial Design

The registry record identifies NCT00491556 as a completed, randomized, parallel-group study with no masking. The recorded enrollment is 102. The phase is listed as NA. The condition is HIV infection, and the record names the University of North Carolina, Chapel Hill, as sponsor. The recorded study start is 2007-10 and primary completion is 2013-06.

The study compares an experimental HAART initiation and de-intensification strategy with standard care. The title and summary describe adolescents with mild immunosuppression initiating HAART and a strategy involving de-intensification to ATV/r. The registry lists “Early Initiation of Highly Active Anti-Retroviral Therapy” and “Standard Care” as interventions. The arm descriptions mention TDF/FTC/ATV/r and AZT/3TC/ATV/r, as well as other recommended NRTI backbone or ATV/r-based regimens. However, the posted arm descriptions end mid-sentence, so complete treatment schedules and eligibility details are not reported in the registry record.

Randomization is relevant because it is intended to support fair comparisons between assigned groups, while the absence of masking describes the study as open-label. These design features do not, by themselves, provide evidence about the size or precision of an outcome effect. The record does not report the allocation method, concealment procedures, stratification factors, or whether outcome assessment was masked.

The study lists a primary endpoint of mean difference in CD4+ T-cell percentage between Week 0 and Week 48. Its stated population is experimental-arm subjects who maintained viral load suppression from Week 24 to Week 152. This population definition matters: it is not described as all randomized participants, nor does the endpoint definition specify a standard-care comparison. The registry record does not report how many participants contributed data to this endpoint or how missing observations were handled.

The secondary outcomes cover CD4+ T-cell counts and subsets, including naïve, central memory, and effector memory cells, across Week 0 to Week 48 and Week 48 to Week 152. The registry record lists 52 outcome measures and 52 analyses. It does not report a complete statistical analysis plan or explain how the endpoint analyses relate to the randomized assignment.

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.

Entry-Week (WK) 48: EXP/Standard Care

Reasons for not completing this period:

Wk 48-152: EXP (On De-Int)/Standard Care

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects who maintained viral load suppression from Week 24 to Week 152 among those randomized to the experimental arm.

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.

Population: 75 subjects were randomized to the experimental arm, however 2 subjects withdrew from the study at the pre-entry visit. Therefore, only 73 experimental arm subjects were available for the baseline analyses.

6. Primary Endpoint

The registry lists the primary outcome as Difference in CD4+ T Cell Percentage Between Week 0 and Week 48, measured over Week 0 and Week 48.

The primary endpoint is the mean difference in CD4+ T-cell percentage between Week 0 and Week 48. The measured quantity is expressed as a percentage of CD4+ T cells, and the registry specifies the mean and standard deviation as the summary measures. It is an immune-cell measure observed over time, rather than a measure of a clinical event.

CD4+ T-cell percentage can describe the composition of circulating immune cells, complementing count-based measures. In general, using a percentage can provide information about the relative proportion of a cell type within the measured population, while a count describes its absolute number. The registry record does not explain why this measure was selected over the other listed immune outcomes.

The specified analysis population is subjects who maintained viral load suppression from Week 24 to Week 152 among those randomized to the experimental arm. That restriction is important when interpreting the endpoint: it does not describe the primary measure across everyone randomized, and the endpoint definition does not state that the reported mean difference compares the experimental and standard-care arms.

The registry record does not report the observed mean change, standard deviation, number of participants with endpoint data, confidence interval, or p-value. It therefore does not show the magnitude or precision of the primary endpoint estimate. The record also does not report how the Week 0 and Week 48 measurements were paired or analyzed, beyond specifying a mean difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a mean difference in a continuous outcome: CD4+ T-cell percentage from Week 0 to Week 48. The statistical meaning of a mean is the arithmetic average of observed values. The standard deviation describes the spread of individual observations around that average; it is not the uncertainty in the estimated mean. The registry names the mean and standard deviation but does not report their values for the primary outcome.

What does a mean difference describe?

A change score compares measurements taken at separate times for the same outcome. A mean change summarizes those individual changes as an average. Its interpretation depends on the unit and the direction of subtraction. The endpoint title says “Difference in CD4+ T Cell Percentage Between Week 0 and Week 48,” but the registry record does not specify the subtraction convention. Without the estimate, its direction and size cannot be interpreted in any case.

In general, measurements at two time points from the same participant are correlated. A paired analysis uses that within-participant relationship; an analysis that treats the measurements as independent does not. The registry record does not specify the method used to calculate or test the primary change, so it is not possible to determine from the record whether the analysis used a paired method, a model, or another approach.

How should an estimate and its uncertainty be read?

In general, a confidence interval gives a range of values compatible with the observed data under the method’s assumptions. A narrow interval indicates more precision than a wide interval, while an interval containing values on both sides of a null value may leave the direction of an effect uncertain. These concepts require an actual estimate and interval to apply. Neither is reported for the primary outcome in the registry record. No p-value is reported, and a p-value alone would not describe the magnitude or clinical importance of an effect.

The study uses random allocation, but the primary endpoint population is defined by a post-randomization condition: maintenance of viral load suppression from Week 24 to Week 152 in the experimental arm. In general, conditioning on a characteristic observed after randomization can change the composition of the analyzed group. Thus, a result limited to this population would answer a different question from an analysis of all randomized participants. The registry record does not report whether an all-randomized analysis was also conducted or how the specified subset was formed.

What is the role of the listed planning assumptions?

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These assumptions are not a substitute for the trial’s original design rationale; that rationale is not reported in the registry record. The illustration is for planning, not observed power. A sample-size calculation cannot establish whether a study’s observed result is precise, and it cannot repair the absence of the endpoint estimate and its uncertainty.

For continuous outcomes, the planning illustration is described in participants per arm for a specified power. The record’s general guidance says time-to-event planning tables use total events, but the primary outcome is continuous. The registry entries do not give the calculated participant requirements or the observed effect used in the illustration, so neither should be inferred. The record also does not report an original target enrollment justification or a statistical power calculation used when the trial was designed.

Why does dispersion matter?

In general, the standard deviation reflects variation among participants. Greater variability makes it harder to estimate a mean precisely when other features are held constant. If a continuous outcome has more variability than a simple model assumes, uncertainty estimates and sample-size planning based on that model may be misleading. The registry identifies standard deviation as the dispersion measure, but provides no primary-outcome value. It does not report whether the distribution was checked or whether an alternative method was used if assumptions were not met.

Some outcomes can have over-dispersion: their variability exceeds what a chosen statistical model expects. This is a general concern for certain count and event data; it is not a finding reported for this trial. The primary endpoint is continuous, and the record does not describe a model, diagnostics, transformations, or robust variance method. No conclusion about these methods can be drawn from the endpoint summary alone.

What can the secondary analyses add?

The listed secondary outcomes cover CD4+ T-cell counts and several subsets at intervals from Week 0 to Week 48 and Week 48 to Week 152. Such measures can describe different aspects of immune-cell change. In general, examining multiple outcomes creates multiplicity: as the number of statistical tests increases, the chance of at least one apparently unusual result can rise if each test is interpreted without adjustment. The registry lists 52 outcome measures and 52 analyses but does not report a multiplicity procedure, hierarchy, or prespecified analysis plan. No claims about statistical significance across these outcomes are possible from the registry entries.

Statistical methods are only one part of interpretation. The relevant population, missing data, adherence, timing, and completeness of reporting also matter. The registry record does not report primary-outcome estimates or enough detail about the analysis to evaluate these features. The appropriate reading is therefore descriptive: the endpoint and some design assumptions are recorded, while the inferential result and several methodological details are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Experimental-Early Initiation of HAART (EXP)")
n   <- c(25)
m   <- c(-10.08)
sp  <- c(5.13)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Experimental-Early Initiation of HAART (EXP)  25  -10.080  5.130  -12.198  -7.962

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 52 outcome measures and 52 analyses, including the primary CD4+ T-cell percentage endpoint and secondary measures of CD4+ counts and cell subsets. When many outcomes or tests are examined, multiplicity is a general statistical concern: interpreting each test separately can increase the chance of at least one apparently notable result. The record does not state whether tests were adjusted, whether outcomes were arranged in a testing hierarchy, or which analyses were prespecified. A statistical analysis plan is not reported in the registry record.

Missing-data methods are also not reported. The registry does not give the number of participants with Week 0 and Week 48 endpoint measurements, explain how incomplete follow-up was handled, or describe any imputation or sensitivity analysis. It does not report participant flow into the primary population defined by viral suppression from Week 24 to Week 152. Without these details, the potential influence of missing observations and population restriction cannot be evaluated.

The primary outcome is defined for experimental-arm subjects who maintained suppression through Week 152, rather than explicitly for all randomized participants. The registry record does not report an intention-to-treat analysis, a per-protocol analysis, or another analysis-population strategy. It also does not explain whether people who did not meet the suppression criterion contributed to other analyses. These omissions limit assessment of how closely the analysis reflects randomized assignment.

The primary result itself—including an estimate, uncertainty interval, and p-value—is not reported in the registry record. No missing-data or multiplicity method can be assessed without those results and supporting details.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: completed suicide (3.7%), cholecystitis (1.3%), pancreatitis (1.3%), neutriphil count decreased (1.3%).

The registry reports serious adverse events for the experimental arm as 2 affected participants among 75 listed at risk, and for standard care as 1 among 27 listed at risk. Other adverse events are reported as 9 among 75 in the experimental arm and 0 among 27 in standard care. These are descriptive counts; they do not, on their own, show that assignment caused an event or that the groups differ reliably.

The record lists Completed Suicide at 3.7%, Cholecystitis at 1.3%, Pancreatitis at 1.3%, and Neutriphil Count Decreased at 1.3% among the leading serious-event terms. It does not specify the arm or denominator for each listed term in the registry entries. The event-term percentages should therefore not be attributed to a particular arm or treated as directly comparable group rates.

Event timing, duration, severity definitions, exposure time, and methods of safety-event collection are not reported in the registry record. Death counts are not reported. These limitations mean the entries provide a limited descriptive account, not a complete comparative safety analysis.

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

The record establishes that this was a randomized, open-label, parallel-group study of HAART management in adolescents with HIV infection. It defines a primary endpoint based on CD4+ T-cell percentage between Week 0 and Week 48 and describes a primary population from the experimental arm that maintained viral load suppression from Week 24 to Week 152. Those details clarify what the study set out to measure, but they do not reveal the endpoint result.

The registry record does not report a mean difference, standard deviation, confidence interval, or p-value for the primary endpoint. It therefore cannot establish whether the measured percentage changed, how large any change was, or how precisely it was estimated. Nor does the primary endpoint definition specify a comparison with standard care. A missing result is not evidence of no change, equivalence, or lack of an effect.

The randomized design supports a comparative framework in principle, but a treatment comparison requires results for the relevant randomized groups and adequate information about the analysis. The primary outcome display is not available as a comparison because fewer than two arms are present for that outcome. The record does not provide a numerical comparative estimate to interpret.

The adverse-event counts and listed terms offer limited descriptive information. They do not establish that one strategy is safer or more harmful, particularly without event timing, arm-specific term detail, and uncertainty estimates. Similarly, the listed immune-cell outcomes do not support conclusions about changes in those measures because numerical results are not reported in the registry record for this interpretation.

Accordingly, the defensible conclusion is about reporting: the design and outcome definitions are recorded, but the primary efficacy estimate and key analytic details are not reported in the registry record. Any stronger conclusion about the direction, size, precision, or clinical significance of the endpoint would go beyond the reported information.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a randomized design and a reported randomized comparison. Random allocation is a design feature intended to support fair comparisons, but the specified primary outcome population includes experimental-arm subjects meeting a later viral-suppression condition. The primary endpoint is therefore not described as an analysis across both randomized arms. This distinction affects which question a result could answer.

The timing of the endpoint and population definition is also important. The measure is a change from Week 0 to Week 48, while the primary population is defined by suppression from Week 24 to Week 152. In general, restricting analysis based on a post-randomization characteristic can alter the composition of the analyzed group. The record does not provide enough detail to assess the implications for this study, making clear reporting of population flow and analytic choices especially relevant.

The registry lists 52 outcome measures and 52 analyses. Multiple endpoints can provide a broad description of immune outcomes, but they also raise questions about prespecification and multiplicity. The record does not report whether or how those issues were addressed. This illustrates why outcome definitions, analysis plans, and numerical estimates with uncertainty are all needed for interpretation.

Finally, the record includes some adverse-event counts but omits key context, including the reported death counts and event timing. Descriptive safety data need denominators, clear event definitions, and suitable comparative analysis to support interpretation. In this case, the registry supports an account of what was measured and some event counts, but not a complete statistical assessment of efficacy or safety.

15. 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 central limitation is that numerical results for the primary endpoint are not reported in the registry record. The mean difference, standard deviation, confidence interval, p-value, and number of participants contributing endpoint data are unavailable. The secondary outcome results are also not included in the registry record for this interpretation, so the listed immune-cell measures cannot be evaluated quantitatively.

The primary population is defined by maintained viral load suppression from Week 24 to Week 152 among experimental-arm subjects, while the endpoint compares Week 0 and Week 48. The record does not explain this selection or report how many subjects met the criterion. It also does not describe an analysis of all randomized participants or provide participant flow by arm. The relationship between the primary analysis population and the randomized comparison is therefore unclear.

The experimental and standard-care arm descriptions are incomplete in the registry record. Although several regimen names and general treatment descriptions are present, the text is truncated and does not provide complete schedules or details of management. The record also does not report allocation concealment, stratification, adherence, outcome-assessment procedures, or the statistical analysis plan.

For the 52 listed outcomes and analyses, multiplicity handling and prespecification are not reported. Missing-data methods are not reported either. Safety reporting is limited: event timing and the arm-specific context for the listed serious-event terms are not given, and death counts are not reported. These gaps prevent a full evaluation of precision, potential bias, and comparative safety from the registry record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r) — NCT00491556.
• Registry record last updated 2017-03-29; status last verified 2016-05.
• Results first posted 2016-06-24.
• 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.

19. Record Summary

NCT00491556 is recorded as a completed, randomized, open-label, parallel-group study with enrollment of 102. It concerns adolescents with HIV infection initiating HAART and compares an experimental initiation and de-intensification strategy with standard care. The primary endpoint is the mean difference in CD4+ T-cell percentage between Week 0 and Week 48 in experimental-arm subjects who maintained viral load suppression from Week 24 to Week 152.

The registry record lists 52 outcome measures and 52 analyses, but does not report the numerical primary endpoint result or its uncertainty. The primary outcome is not available as a two-arm comparison. Adverse-event counts are recorded by arm, while death counts and important safety-analysis details are not reported in the registry record. The available information defines the study question and selected design features, but does not support a quantitative conclusion about the primary outcome.