Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected ART Experienced Children and Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected ART Experienced Children and Adolescents (NCT00766597), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Suspected Adverse Drug Reaction Leading to Treatment Termination.

2. Clinical Question

The study asked whether vicriviroc could be evaluated for safety, tolerability, pharmacokinetics and antiviral activity when used in combination regimens in HIV-1-infected children and adolescents with prior antiretroviral therapy experience. The registry describes participants with CCR5-tropic virus; the primary endpoint population is specified more narrowly as participants who started treatment in Step II.

That safety question is distinct from the broader study objectives. The registry’s brief summary frames the study around the safety and effectiveness of vicriviroc, while its official title also identifies pharmacokinetics, tolerability and antiviral activity. Secondary outcomes include virologic failure, changes in co-receptor tropism, CD4 counts and percentage, polymerase genome and envelope sequence, and plasma HIV RNA PCR.

Because there is no concurrent control group, the study is not set up to compare outcomes under vicriviroc with outcomes under another treatment. Its described purpose is evaluation within the enrolled group, not estimation of a comparative treatment effect. The registry record does not report a primary endpoint result, so the number of participants meeting that endpoint cannot be stated from the recorded results.

3. Trial Design

This was a Phase I/II, open-label, single-group study. The record lists allocation as not applicable and masking as none. Participants received vicriviroc in tablet form (20/30 mg) or liquid form (1 mg/ml), in combination regimens. The described population was HIV-1-infected, antiretroviral-therapy-experienced children and adolescents with CCR5-tropic virus.

The registry records an enrollment of 9. The study started in 2009-08, reached primary completion in 2010-07, and has completed status. These dates and status describe the registry record; they do not, by themselves, establish when individual participants started or stopped treatment.

The primary endpoint is a count of participants with a suspected adverse drug reaction leading to treatment termination. Its timeframe is from study entry to Week 24 or early study termination, whichever occurred earlier. The endpoint description identifies the relevant group as participants with the specified infection and treatment history who started treatment in Step II. The record does not give a numerical primary endpoint result.

Secondary outcomes cover virologic failure, co-receptor tropism, CD4 measures, viral sequence measures and plasma HIV RNA PCR. The registry record lists 9 outcome measures and 0 analyses. It does not report detailed results or analysis methods for those secondary outcomes in the information.

The lack of a control group matters for interpretation. Outcomes can describe what was observed among participants receiving the study regimen, but the design cannot separate changes associated with vicriviroc from changes that might have occurred for other reasons. The registry record does not report a randomized comparison, and the adverse-event group summaries should not be treated as comparative estimates between treatment arms.

The record identifies the National Institute of Allergy and Infectious Diseases (NIAID) as sponsor. It does not report a sample-size justification, detailed dosing schedule, or a full statistical analysis plan. Those omissions limit how much can be inferred about planned precision, study conduct and the intended analysis beyond the endpoint descriptions.

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: In Step I, 9 participants under Cohort I were screened for evaluation for co-receptor tropism. Five participants did not have the required tropism and were discontinued from the study. Only 4 participants had the CCR-5-tropic virus tropism, and thus were eligible to go to Step II and were assigned to receive the study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The HIV-1 infected antiretroviral therapy experienced participants with CCR5-tropic virus who started treatment in Step II.

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: The HIV-1 infected antiretroviral therapy experienced participants With CCR5-tropic virus who started treatment in Step II

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Suspected Adverse Drug Reaction Leading to Treatment Termination, measured over From study entry to Week 24 or the early study termination whichever occurred earlier.

The primary endpoint counts participants with a suspected adverse drug reaction that led to treatment termination. It is a participant-count endpoint: the event of interest is not every symptom or laboratory abnormality, but a suspected drug reaction linked to stopping study treatment. This makes the endpoint a measure of treatment-limiting safety as defined by the protocol description.

The observation period runs from study entry through Week 24, unless the study ended earlier for a participant. The endpoint population is described as participants with HIV-1 infection, prior antiretroviral therapy experience and CCR5-tropic virus who started treatment in Step II. The registry record does not state the number of participants who met this endpoint.

Safety studies use treatment-termination outcomes to identify events important enough to affect continued exposure. Such an endpoint can be informative about tolerability, but it does not capture the full range or severity of all adverse events. Nor does its count alone establish that vicriviroc caused an event: the endpoint uses the term “suspected,” and the record says the Study Team determined relationship for serious adverse events in connection with start, stop and pause rules.

The record also describes required reporting of signs, symptoms and laboratory abnormalities of at least Grade 2, and fever at all grades. Those reporting rules are not themselves the primary endpoint. They define elements of adverse-event collection and grading, whereas the primary endpoint requires suspected drug reaction and treatment termination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with no masking. This is a design description, not a statistical test. In a single-group study, the outcomes characterize participants receiving the study intervention; without a concurrent comparator, the data do not directly estimate how outcomes would differ under another regimen. Open-label means treatment assignment was not masked, but the record does not describe how that feature affected outcome assessment.

What does the primary endpoint count?

The primary outcome is a number of participants, rather than a continuous measurement or a time-to-event estimate. A participant qualifies only if there was a suspected adverse drug reaction leading to treatment termination, according to the endpoint wording. That definition is narrower than “any adverse event.” The collection rules described in the record cover signs, symptoms and laboratory abnormalities of at least Grade 2, as well as fever at all grades, but an event being reportable does not automatically mean it meets the primary endpoint.

The timeframe is from study entry to Week 24, or earlier study termination if that occurs first. A defined observation window helps specify which events are relevant to the endpoint. The registry does not report how individual follow-up was handled in the analysis, whether all participants had complete observation through the stated window, or how missing endpoint status was treated.

How should event counts be read?

A count describes the observed number meeting a stated event definition. When a denominator is also reported, the at-risk count identifies the group used for that particular summary. The listed safety summaries should be read as event counts among their stated at-risk participants, not as estimates for every enrolled participant unless the record says those populations match. Here the record gives enrollment of 9 and safety at-risk counts of 4. Why those counts differ is not reported in the registry record.

For a binary event, an uncertainty interval can be used generally to show how imprecisely an underlying event frequency is estimated from observed data. It reflects sampling uncertainty under the chosen statistical method and assumptions; it does not correct limitations such as a missing comparator, incomplete follow-up or an unclear analysis population. The record does not report a confidence interval for the primary endpoint, and no interval should be inferred from the counts alone.

What can a comparison establish?

Comparative analysis asks whether outcomes differ between groups, but a meaningful treatment comparison depends on how groups were formed and on the analysis plan. Random allocation can help balance factors that affect outcomes, while an uncontrolled single-group design cannot provide that protection through a concurrent control. This study’s allocation is recorded as not applicable, and the model is listed as single group. Therefore, the posted information supports descriptive interpretation rather than a treatment-versus-control estimate.

Even in a randomized comparison, a statistical difference would need interpretation alongside effect size, uncertainty, endpoint definition and clinical context. In an uncontrolled study, observed events and changes may have multiple explanations. The registry record does not report a comparative analysis, adjusted estimates or statistical tests for the listed outcomes.

Why do safety definitions and attribution matter?

Adverse-event grading and relationship assessment answer different questions. Grading categorizes severity; attribution assesses whether an event is considered related to study drug. The record identifies the DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009), and says expedited reporting followed Version 2.0 of the DAIDS Expedited Adverse Event Manual. It also states that the Study Team determined the relationship of serious adverse events for start, stop and pause rules, using categories from “Not related” through “Definitely related.”

These procedures describe how events were to be classified and handled, but do not establish the actual attribution for each event. The registry does not list serious-event terms or the primary endpoint result. A reader should not infer causality from the mere presence of an event in a safety category.

What does the registry say about statistical planning?

The registry record lists 0 analyses. A detailed statistical plan, sample-size justification, interim-analysis plan and method for handling multiple outcomes are not reported in the registry record. The study title and outcome list identify scientific aims, but do not specify statistical models or decision rules. The sample-size illustration described with the posted material is a planning exercise based on an observed effect, not the study’s own design; such planning figures should not be read as observed power or as evidence that the trial had adequate precision.

In general, planning calculations depend on an assumed effect, variability or event frequency, significance level, allocation and analysis method. Changing those assumptions changes the resulting sample-size requirement. A planning illustration can help explain scale, but it cannot replace a documented design rationale or analysis plan. No numerical planning results are stated in the registry record.

Why can over-dispersion matter?

For outcomes that count events, simple models may assume that variability follows a particular relationship to the mean. Over-dispersion occurs when observed variability is greater than that assumption allows; if ignored, uncertainty can be understated. This is a general statistical issue, not a reported feature of this study. The primary endpoint is a count of participants with an event, and the registry does not report a model or dispersion estimate for it.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Vicriviroc in Tablet Form (20/30 mg) or Liquid For")
n      <- c(4)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Vicriviroc in Tablet Form (20/30 mg) or Liquid For  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including virologic failure, co-receptor tropism, CD4 counts and percentage, sequence changes, and plasma HIV RNA PCR, in addition to the primary safety endpoint. When many outcomes are examined, there is a general risk that some findings may appear notable by chance, especially if multiple statistical tests are performed. A prespecified testing hierarchy or multiplicity adjustment can address some of that concern, but the registry record does not report a multiplicity plan or statistical testing hierarchy.

The record lists 9 outcome measures and 0 analyses. It does not provide a detailed statistical analysis plan, so it is not possible to determine from the registry record which outcomes were included in formal analyses, whether any multiplicity adjustment was used, or how outcome definitions were applied in analysis. A listed outcome should not be assumed to have a reported result.

Missing-data handling is also not reported in the registry record. The description gives an endpoint observation window through Week 24 or early study termination, but does not state how participants with incomplete follow-up or unknown endpoint status were handled. The 9 enrolled participants and the 4 participants at risk in each safety category do not, by themselves, explain the population used for the primary endpoint. No participant-flow account or analysis-population definition is stated.

These omissions matter because the interpretation of counts depends on who was assessed, for how long, and under what rules. Without those details, results cannot be reconstructed or assessed for sensitivity to missing observations. The primary endpoint count itself is not reported in the registry record, so neither its precision nor the effect of any missing data can be evaluated.

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 non-serious adverse event terms

The posted serious adverse-event summary lists 0 participants affected among 4 at risk in the vicriviroc group. For other adverse events, it lists 4 participants affected among 4 at risk. These are distinct categories in the safety summary; the other-adverse-event count should not be read as a count of serious events.

The death count is not reported in the registry record. The list of top serious adverse-event terms is empty, so no serious-event descriptions are available in that summary. The figures do not give event timing, severity details for other events, or the number of events per participant.

These safety counts are not the primary endpoint result. The primary endpoint specifically concerns suspected adverse drug reactions leading to treatment termination in participants who started treatment in Step II. The record does not state how many participants met that definition. Nor should event counts alone be treated as proof that an event was caused by study drug: the record describes an attribution process, but does not provide event-level attribution results.

Because the study has no concurrent control group, these summaries describe events in the listed group and do not establish comparative safety against another regimen. They are also not a complete account of all safety outcomes without further detail on event definitions and follow-up.

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

The registry record establishes that this was a completed, open-label, single-group Phase I/II study of vicriviroc in antiretroviral-therapy-experienced children and adolescents with CCR5-tropic HIV-1. It describes a primary safety question focused on suspected adverse drug reactions leading to treatment termination, along with secondary virologic, immunologic and sequence outcomes. The posted safety summary records 0 serious adverse events among 4 at risk and 4 participants with other adverse events among 4 at risk.

Those observations do not give the primary endpoint result. They therefore cannot show how many participants stopped treatment because of a suspected adverse drug reaction. They also do not reveal the details or attribution of individual events. The death count is not reported in the registry record.

The study’s design sets important boundaries on interpretation. With no control group, the observed outcomes cannot establish what would have happened under an alternative regimen. With no reported primary analysis, confidence interval, or detailed analysis plan, the precision and statistical handling of the primary endpoint cannot be assessed. The record does not provide enough information to infer the reason for the difference between the enrollment figure and the safety at-risk counts.

In general, a small descriptive study can document whether events were recorded under a specific study regimen and can inform questions for further research. It cannot, on its own, isolate treatment effects from other influences or establish comparative effectiveness. This is a statistical interpretation of the record, not a treatment recommendation or a conclusion about clinical benefit.

The appropriate conclusion is therefore limited: the registry describes the intervention, population, endpoint and some safety counts, but does not report a primary endpoint result or comparative analysis. Any stronger claim about treatment-related risk, antiviral activity or relative safety would go beyond the results recorded.

14. Why This Trial Matters Statistically

This trial matters statistically because it shows how a safety-focused question can be clear in definition while still lacking a reported result needed to answer it. The primary outcome is specific: suspected adverse drug reaction leading to treatment termination within the stated observation period. Yet the registry record does not give the number meeting that definition. Separate serious and other adverse-event counts cannot fill that gap because they use different categories.

The single-group design also illustrates the distinction between description and comparison. The study can document events among participants who received vicriviroc, but it cannot estimate a controlled contrast with another regimen. Statistical significance, even if reported for a within-group change, would not by itself resolve that design limitation. Here the record lists no analyses.

The safety summary also emphasizes why denominators and analysis populations need clear descriptions. Enrollment is recorded as 9, while the event summaries identify 4 participants at risk. Both figures should be retained in their stated contexts; the record does not explain their relationship. Assuming that they refer to the same population or that one reconciles the other would add information not reported.

Finally, a registry entry can convey methods and outcome definitions without supplying enough statistical detail to evaluate precision, missingness or multiplicity. For researchers, this underscores the value of transparent results reporting: event counts, denominators, endpoint-specific analysis populations, uncertainty estimates and analysis methods each answer different questions. The available record supports careful descriptive reading, but not a broader comparative conclusion.

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.

Several limitations are specific to the information recorded for this study. The primary endpoint is defined, but its result is not reported in the registry record. This prevents assessment of the frequency of treatment termination for suspected adverse drug reactions and of the precision of that estimate.

The design is open-label and single-group, with allocation not applicable. There is no concurrent comparator described. As a result, the safety counts cannot be interpreted as a comparative estimate, and observed changes in secondary outcomes cannot be attributed to vicriviroc on the basis of this design alone.

The registry records enrollment of 9, whereas the serious and other adverse-event summaries each use 4 at-risk participants. The record does not explain this difference. It also does not report a participant-flow account, the analysis population for each outcome, or how incomplete follow-up was handled. These gaps make it difficult to understand which participants contributed to each result.

Safety reporting is limited in the posted information: the death count is not reported, the serious-event term list is empty, and event-level timing and attribution are not stated. The primary endpoint should not be conflated with these broader safety categories.

The record lists 9 outcome measures and 0 analyses, but does not report a statistical analysis plan, multiplicity approach, sample-size justification or interim-analysis plan. These are not evidence that particular methods were or were not used; their status is simply not reported in the registry record. The record also does not provide detailed results for the secondary outcomes, limiting interpretation of the study’s antiviral and immunologic aims.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected ART Experienced Children and Adolescents — NCT00766597.
• Registry record last updated 2021-11-05; status last verified 2015-12.
• Results first posted 2016-02-01.
• 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

NCT00766597 is a completed, open-label, single-group Phase I/II study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It evaluated vicriviroc in combination regimens in HIV-1-infected, antiretroviral-therapy-experienced children and adolescents with CCR5-tropic virus. The registry records enrollment of 9, a start in 2009-08 and primary completion in 2010-07.

The primary endpoint counts participants with a suspected adverse drug reaction leading to treatment termination through Week 24 or earlier study termination. Its result is not reported in the registry record. The safety summary lists 0 serious adverse events among 4 at risk and 4 participants with other adverse events among 4 at risk; the death count is not reported.

Secondary outcomes cover virologic, immunologic and viral sequence measures. The registry lists 9 outcome measures and 0 analyses. With no concurrent comparator and limited posted results, the record supports descriptive interpretation of the listed safety counts, not a comparative treatment conclusion.