Enhancement by Poly-ICLC During HIV-1 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enhancement by Poly-ICLC During HIV-1 Infection (NCT02071095), a randomized phase 1, phase 2 study. The primary outcome is Number Participants With Adverse Events.

2. Clinical Question

The trial record describes an investigation of Poly-ICLC as an addition to existing HIV medications. Its rationale concerns whether an immune adjuvant might be useful in future therapeutic-vaccine research, but no vaccine was given in this study. That distinction matters: the posted primary endpoint is safety-focused, while the background describes a broader research motivation involving immune responses and persistent HIV.

The comparison is between the Poly-ICLC arm and the normal-saline arm in a randomized, double-masked, parallel study. The registry lists enrollment as 15. The results section reports the primary endpoint separately by arm, with 12 participants in the Poly-ICLC arm and 3 in the normal-saline arm. The record does not explain the difference between the enrollment field, arm-description figures, and result counts.

The primary question is therefore narrow: what adverse-event counts were posted for these two groups, and how much can those counts tell us about safety? The results can describe the recorded counts, but the registry record does not report an adjusted comparison, uncertainty interval, or analysis method for a between-arm effect.

3. Trial Design

This was a randomized, double-masked, parallel-group phase 1/phase 2 study. The registry lists 15 participants as the enrollment and marks the trial completed. Its listed start is 2014-04, and its primary completion date is 2016-07-26. Those record details describe the trial's status and structure; they do not provide a statistical analysis plan.

Participants were assigned to the Poly-ICLC or normal-saline arm. The intervention descriptions specify subcutaneous injections on day 1 and day 2. The Poly-ICLC description states 1.4 mg per injection. The registry does not report the randomization procedure, allocation ratio as planned, concealment method, or how masking was maintained. “Double” is the recorded masking designation, but which people were masked is not reported in the registry record.

The arm descriptions state “Arm A (N=15)” for Poly-ICLC and “Arm B: (N=5)” for normal saline. Separately, the posted primary-outcome results list 12 participants for Arm A and 3 for Arm B. The registry does not explain why these figures differ or whether the arm-description N values refer to planned enrollment, another group, or something else. They should not be treated as interchangeable with the result denominators.

The primary outcome is the number of participants with adverse events, with a timeframe of up to 48 weeks. The registry also lists four secondary outcomes: plasma IP-10 level, CD8 CD38 mean fluorescence, NK cell number, and percent change in CD4+ Tcell-associated HIV-1 RNA compared with baseline. However, the record's analysis listing reports no posted analyses. Results for those secondary outcomes are not reported in the registry record.

The record describes the study as randomized and double-masked, but details needed to assess implementation and analysis are absent. The planned sample-size justification and the statistical analysis plan are not reported in the registry record.

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.

Overall Study

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 Number Participants With Adverse Events, measured over Up to 48 weeks.

The primary endpoint is the number of participants with adverse events, reported as a count of participants and assessed over a timeframe of up to 48 weeks. In the posted results, the Poly-ICLC arm has 12 participants and 11 with the endpoint; the normal-saline arm has 3 participants and 3 with the endpoint.

A count of participants with an event is a binary-outcome summary: each participant is classified according to whether the event occurred, and the arm result records how many participants met that definition. This is different from counting the total number of separate events. A participant may experience more than one event, but the primary endpoint as described counts participants, not event episodes.

Safety is an important focus in a phase 1/phase 2 study of an investigational intervention. A count of participants with adverse events provides a direct description of how many participants had at least one recorded event under the endpoint definition. It does not, by itself, describe event severity, duration, relatedness to treatment, or the number of events per person. Those details require distinct outcome definitions or additional summaries.

The registry's primary-outcome description says “Safety measured by number of participants with adverse events.” It does not give a more detailed operational definition of which events were included, how attribution was determined, or how missing safety observations were handled. The posted counts are therefore best read as the registry's summary of the stated endpoint, not as a complete account of every safety dimension.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this?

General: A count of participants with an event is a binary endpoint summarized by the number who experienced the event and the number assessed. It differs from an event count, where one participant can contribute several events. Here the registry names the endpoint as the number of participants with adverse events and gives arm denominators alongside counts. That pairing is essential: a count alone does not show how many people were represented in the arm result.

The posted outcome lists 11 participants with the endpoint among 12 in the Poly-ICLC arm and 3 among 3 in the normal-saline arm. The registry does not report an adjusted effect measure, an uncertainty interval, or a p-value. Without those, the comparison is descriptive. Readers should not infer a population-level contrast simply from the fact that the arm counts differ.

What does uncertainty mean?

General: A confidence interval expresses the range of values reasonably compatible with the data and a specified statistical method. Its width depends on the amount of information in the data and on the analysis. With small groups, estimates for binary outcomes can be imprecise; a reported count does not eliminate that uncertainty. An interval can also help distinguish a precise estimate from one that leaves many possible values plausible.

No confidence interval is reported for this primary outcome. This means the registry record does not show how much uncertainty an analysis would attach to an arm-specific estimate or to a between-arm contrast. It would be inappropriate to present an interval or an inferential conclusion that is not in the record.

Why can the arm sizes matter?

General: Comparing groups of different sizes affects how much information each group contributes. A result based on fewer participants tends to be less stable than one based on more participants, especially when the endpoint is binary and the number of possible outcome patterns is limited. Statistical methods can accommodate unequal group sizes, but the choice of method and its assumptions matter.

The posted primary-outcome result groups contain 12 and 3 participants. The record does not report a model or test that accounts for the group sizes, nor does it provide a planned allocation ratio. The record also gives arm-description N values of 15 and 5, without explaining how those relate to the endpoint denominators. This limits assessment of the analysis set and of the intended comparison.

What can randomization and masking establish?

General: Random assignment is intended to reduce systematic differences between groups at the start of a trial, on average. Masking can reduce the influence of knowledge about assignment on care, measurement, or reporting, depending on who is masked and how the procedure is implemented. These design features do not guarantee that every source of bias is absent, and they do not replace a transparent outcome definition or analysis plan.

The registry records randomized allocation and double masking. It does not report the randomization method, who was masked, allocation concealment, or whether masking was assessed. Therefore, the design labels can be described, but implementation cannot be evaluated from the record.

What would an analysis plan clarify?

General: A statistical analysis plan identifies the target comparison, outcome definition, analysis population, method for estimating effects, treatment of missing observations, and any planned handling of multiple outcomes. For binary outcomes, possible approaches differ in the effect measure they estimate and in assumptions about the data. A prespecified method also helps readers distinguish planned analyses from choices made after results are known.

The registry record does not report the primary-outcome method or a statistical analysis plan. It reports no posted analyses. It is therefore not possible to identify whether the sponsor intended a particular test, whether the analysis was adjusted, or how any deviations from the planned approach were addressed. No method should be attributed to the investigators without documentation.

How should the sample-size section be read?

General: A sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability or event rates, significance level, allocation, and analysis method. It does not describe the observed evidence after a trial is complete. In particular, a sample-size illustration is not “observed power,” and it cannot substitute for an effect estimate with an uncertainty interval.

The sample-size section is a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. It considers effects stated as fractions of the observed effect. These assumptions describe the illustration, not the trial's own design justification. The registry record does not report the trial's sample-size justification, and no calculated planning values are reported. The illustration should not be interpreted as evidence that the trial was adequately powered or as a post-trial measure of whether an effect was detected.

Why is over-dispersion relevant in general?

General: Over-dispersion means that observed variability is greater than a model assumes. It is especially relevant to outcomes modeled as counts, where a basic model may expect a particular relationship between the mean and variance. If over-dispersion is ignored, standard errors may be too small and uncertainty may appear understated. The posted primary endpoint is a participant count with an event, not a total count of repeated event episodes, and the registry does not describe a count model or any over-dispersion assessment. It is therefore not possible to say that over-dispersion was assessed or relevant to the sponsor's analysis.

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("Arm A: Poly-ICLC", "Arm B: Normal Saline")
n      <- c(12, 3)
events <- c(11, 3)
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  Arm A: Poly-ICLC  12  11  91.7  61.5  99.8  64.6  98.5  64.0  98.1
ARM  Arm B: Normal Saline  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety endpoint and four secondary outcomes: plasma IP-10 level, CD8 CD38 mean fluorescence, NK cell number, and percent change in CD4+ Tcell-associated HIV-1 RNA compared with baseline. Multiple outcomes can create a multiplicity issue when several hypotheses are tested: the chance of at least one false-positive finding can increase if tests are treated independently without an appropriate strategy. General: trial plans may address this by defining a primary outcome, ordering secondary questions, or adjusting inference, but no such approach should be assumed.

The registry record does not report a multiplicity procedure, outcome hierarchy beyond identifying the primary endpoint, or a statistical analysis plan. It lists 0 posted analyses, so results for the secondary outcomes are not reported in the registry record. No adjustment—or absence of adjustment—can be attributed to the investigators from this information.

Missing-data handling and analysis populations are also not reported in the registry record. The result denominators are stated, but the record does not say whether they represent everyone randomized, everyone treated, or a defined safety population. It does not explain whether any participants lacked endpoint information, how missing observations were handled, or whether any participants were excluded from an analysis. The enrollment field and arm-description figures do not resolve those questions. Without this detail, readers cannot assess how the posted results relate to all randomized participants or whether missingness could affect interpretation.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fatigue (100.0%), pain (83.3%), headache (66.7%), erythema (41.7%), fever (33.3%).

The registry's serious adverse-event summary reports 11 affected participants among 12 at risk in the Poly-ICLC arm and 3 among 3 at risk in the normal-saline arm. It records 0 deaths in each arm. These figures are counts of participants, not counts of separate event episodes, and the registry does not report an inferential comparison or uncertainty interval for them.

The listed serious adverse-event terms are Fatigue at 100.0%, Pain at 83.3%, Headache at 66.7%, erythema at 41.7%, Fever at 33.3%, and Malaise at 33.3%. The record does not state the denominator for these percentages, whether the terms can overlap within participants, or how event seriousness and attribution were determined. They therefore describe the listed registry entries but cannot be interpreted as arm-specific rates from the available information.

These serious-event figures should be distinguished from the primary endpoint's broader wording, “participants with adverse events.” Although the counts match within each arm, the registry does not explain whether the categories share a definition. The counts alone do not establish cause, severity distribution, or comparative safety.

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

The posted results show how many participants in each arm were recorded with the primary adverse-event endpoint: 11 of 12 in the Poly-ICLC arm and 3 of 3 in the normal-saline arm. The serious adverse-event summary also records 11 of 12 and 3 of 3, respectively, and 0 deaths in each arm. These are descriptive findings from the registry record; the record does not report an inferential comparison or uncertainty interval.

The results do not establish that Poly-ICLC caused or prevented adverse events, nor do they show that the two arms have equivalent safety. The recorded design is randomized and double-masked, but the posted results are small group counts and lack details on analysis methods, missing observations, and endpoint definitions. Design labels cannot fill those gaps.

The trial's background describes an interest in immune enhancement and in future therapeutic vaccines, while also stating that no vaccine was given. The primary outcome is safety-focused. It does not measure whether a therapeutic vaccine works, whether the viral reservoir changed, or whether HIV infection was cured. The secondary outcomes listed in the registry concern immune and HIV-related measures, but their results are not reported in the registry record.

More broadly, an adverse-event count is only one component of a safety assessment. It does not show the number of events per person, time to onset, duration, severity distribution, or treatment relatedness unless those are separately defined and reported. The registry does not provide those details in a way that permits a fuller interpretation of these counts.

The most defensible conclusion is limited: the registry posts the stated counts for the recorded groups and timeframe. It does not provide enough information to quantify the precision of a treatment contrast or to support a general claim about safety beyond those observed participants.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it pairs a randomized, double-masked design with a small posted result set and a safety endpoint summarized as participant counts. It illustrates why a study design label and an outcome count are not sufficient on their own for comparative interpretation. Readers also need the endpoint definition, analysis population, method, and a measure of uncertainty.

The numbers in the record also highlight the importance of separating enrollment descriptions from analysis denominators. The enrollment field lists 15; the arm descriptions state N=15 and N=5; and the posted primary-outcome results list 12 and 3 participants. The registry record does not explain these differences. Clear reporting of who entered each analysis and why denominators differ is important for reproducibility and for assessing possible selection or missing-data concerns.

Another statistical lesson is the distinction between a planning exercise and evidence from an observed comparison. A sample-size illustration based on the observed effect is not the trial's design justification and is not observed power. It cannot replace a reported estimate and interval. This matters especially when the record does not provide the planned sample-size rationale or an analysis plan.

Finally, a safety endpoint is not a single universal measure. A count of participants with any adverse event, a count of serious events, and a list of event terms answer related but different questions. The record's primary endpoint and serious-event summary should not be conflated simply because their arm counts match. Transparent definitions and denominators would make the safety results easier to interpret.

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 registry record leaves several trial-specific questions unresolved. It states enrollment as 15, while the arm descriptions give N=15 for Poly-ICLC and N=5 for normal saline; the primary-outcome results list 12 and 3 participants. No explanation is reported for these figures, so the exact relationship among enrolled, assigned, treated, and analyzed groups cannot be established.

The primary outcome is described as the number of participants with adverse events, but the record does not give an operational definition of an adverse event, explain ascertainment, or report how events were attributed to treatment. The separate serious-event summary lists the same participant counts as the primary endpoint, but does not explain whether the two summaries use the same criteria. The denominator and overlap rules for the listed event-term percentages are also not reported.

No primary-outcome analysis method, effect estimate, confidence interval, p-value, or statistical analysis plan is reported. Missing-data handling, analysis populations, and the planned sample-size justification are not reported in the registry record. The record does not describe the randomization method, who was masked, or how masking was implemented. These omissions limit assessment of both bias and precision.

The study is marked completed, but results for its four listed secondary outcomes are not reported in the registry record. The posted analyses listing is empty. Consequently, the immune and HIV-related outcomes described in the registry cannot be evaluated here, and the safety counts alone do not answer the broader research questions in the study background.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Enhancement by Poly-ICLC During HIV-1 Infection — NCT02071095.
• Registry record last updated 2018-03-13; status last verified 2018-02.
• Results first posted 2018-03-13.
• 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

This completed randomized, double-masked, parallel phase 1/phase 2 study compared subcutaneous Poly-ICLC with normal saline in adults with chronic HIV-1 infection. The primary endpoint was the number of participants with adverse events over up to 48 weeks. The posted results report 11 of 12 participants for Poly-ICLC and 3 of 3 for normal saline.

The serious adverse-event summary reports the same participant counts in each arm and 0 deaths in each arm. The registry lists four secondary outcomes, but their results are not reported in the registry record. It also does not report an inferential comparison, uncertainty interval, analysis plan, missing-data approach, or sample-size justification. The posted counts therefore support a descriptive account of the registry results, not a quantified conclusion about comparative safety.