Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED) (NCT03921424), a randomized phase 3 study. The primary outcome is Percentage of Participants With a Solicited Injection-Site Adverse Event Following Vaccination With V114 or Prevnar 13™.

2. Clinical Question

The study concerns vaccination in children infected with HIV and combines safety monitoring with measures of immune response. Its primary endpoint focuses on specified local reactions after the first study vaccination: redness or erythema, a hard lump or induration, tenderness or pain, and swelling. The later PNEUMOVAX™23 vaccination is part of both study groups’ schedules, and the registry lists further safety and immunogenicity outcomes after that vaccination as well.

The central comparison is between the V114 and Prevnar 13™ vaccination groups. Because both groups were scheduled to receive PNEUMOVAX™23 eight weeks after their first vaccination, the initial comparison concerns the assigned first vaccination within a shared subsequent schedule. The primary endpoint concerns reported local events during a defined period, not a measure of immune response or a broad assessment of every possible adverse event.

The registry record describes the objectives and endpoint but does not report primary endpoint results or a numerical comparison between groups. Accordingly, the registered question can be described, but the available record does not establish the observed size or precision of any difference in injection-site events.

3. Trial Design

This was a Phase 3, randomized, parallel-group, active-comparator-controlled study. The registry describes quadruple masking and enrollment of 407 participants. Participants were randomly assigned in a 1:1 ratio to receive V114 or Prevnar 13™ as their first vaccination. Both groups were scheduled to receive PNEUMOVAX™23 eight weeks later.

The V114 group was scheduled to receive a single 0.5 mL intramuscular injection of V114 on Day 1 and a single 0.5 mL intramuscular injection of PNEUMOVAX™23 at Week 8. The comparator group was scheduled to receive a single 0.5 mL intramuscular injection of Prevnar 13™ on Day 1 and the same stated PNEUMOVAX™23 schedule at Week 8. The active comparator means the main initial comparison was between two vaccination regimens, rather than between vaccination and no vaccination.

The stated primary safety endpoint was the percentage of participants with a solicited injection-site adverse event through 14 days after Vaccination 1. Solicited events were redness or erythema, hard lump or induration, tenderness or pain, and swelling. The registry also lists solicited systemic and injection-site adverse events following PNEUMOVAX™23, as well as serotype-specific opsonophagocytic activity titers and IgG geometric mean concentrations at specified post-vaccination assessments.

The study began on 2019-11-05, had a primary completion date of 2021-05-03, and is listed as completed. These dates describe the registry’s study timeline and do not provide an outcome result. The record gives the enrollment and planned group allocation but does not report the number who completed follow-up, the number analyzed for each secondary outcome, or reasons for any missing observations.

The brief summary says there were no formal hypotheses. The protocol’s detailed statistical plan, including any sample-size justification or interim analyses, is not reported in the registry record. The posted results contain 0 analyses, so the registry record does not provide an analyzed numerical estimate for the primary endpoint comparison.

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: 407 participants were randomized in a 1:1 ratio to receive either V114 or Prevnar 13™ on Day 1 and PNEUMOVAX™23 at Week 8.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 dose of study vaccination were analyzed.

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 Percentage of Participants With a Solicited Injection-Site Adverse Event Following Vaccination With V114 or Prevnar 13™, measured over Through 14 Days after Vaccination 1 (Up to Day 14).

The primary endpoint is the percentage of participants with a solicited injection-site adverse event through 14 days after Vaccination 1. The specified local events are redness or erythema, hard lump or induration, tenderness or pain, and swelling. The registry describes the events as adverse events temporally associated with study intervention, whether or not considered related to the intervention.

A percentage expresses how common the defined event was in a group, using the number of participants with an event relative to the relevant group size. This is useful for a safety endpoint because it gives an interpretable summary of the frequency of prespecified symptoms during a defined observation period. It differs from counting all medical occurrences, since the primary endpoint is restricted to solicited injection-site events and a specific post-vaccination window.

The stated analysis population includes all randomized participants who received at least 1 dose of study vaccination. The endpoint therefore has a defined population and time frame in the record, but no primary event counts, percentages, confidence intervals, or group comparison are reported. The registry record also does not report how multiple local symptoms in one participant were handled for the overall endpoint, or how missing diary or follow-up information was treated. Those details matter when interpreting a percentage because they determine how participants and events contribute to the estimate.

The endpoint is one part of the study’s broader evaluation. It does not by itself summarize systemic adverse events, serious adverse events, or antibody and functional immune-response measures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the main endpoint as a percentage and specifies a confidence interval as its dispersion measure. It also states that no formal hypotheses were planned. The record has 0 analyses, so it does not display the primary endpoint estimates or statistical tests. The concepts below explain how such summaries are generally interpreted; they do not describe unreported procedures from this trial.

What does a percentage measure?

General: A percentage for a binary outcome represents the share of participants classified as having the event among those included in the analysis. For this endpoint, the event definition is a solicited injection-site adverse event during the specified follow-up period after the first vaccination. A percentage is straightforward to communicate, but its interpretation depends on consistent event ascertainment, a clear denominator, and an explicit approach to participants whose event status is unknown.

The registry names the primary analysis population as randomized participants who received at least 1 dose of study vaccination. It does not give primary endpoint numerators or analyzed denominators. The adverse-event entries list separate at-risk counts for the safety summaries, but those should not be substituted for the missing primary endpoint results: the summaries cover different event categories and, for some entries, a different vaccination period.

What does a confidence interval add?

General: A confidence interval conveys uncertainty around an estimate arising from sampling variability under the method used. A narrower interval indicates greater precision than a wider interval for the same type of estimate, while an interval that spans a range of plausible values can make clear that the estimate is not exact. A confidence interval does not describe all sources of uncertainty, such as incomplete outcome reporting, measurement differences, or limitations in how well the study population represents other groups.

The primary endpoint specifies a 95% confidence interval, but the registry does not post the interval’s bounds or the percentage estimate. Consequently, readers cannot assess the primary outcome’s precision or compare the uncertainty around the two groups from this record.

How should an arm comparison be understood?

General: In a randomized study, a comparison between groups can describe how outcomes differed among participants assigned to the study regimens. The estimate and its uncertainty are more informative together than either alone. Random assignment supports a structured comparison, but it does not eliminate the need to examine missing outcomes, adherence, outcome definitions, and the analysis population. A numerical group difference cannot be reconstructed from the registry’s descriptions alone.

The trial uses an active comparator and the groups share a later PNEUMOVAX™23 vaccination. The primary endpoint is assessed after the first vaccination, which gives it a defined temporal relation to the assigned first vaccine. The registry does not provide an estimate for that comparison or specify a model used to analyze it.

Why can variability affect statistical summaries?

General: For binary outcomes, the observed proportion varies from sample to sample. The amount of uncertainty depends in part on how many participants contribute usable outcome information and how common the event is. A confidence interval reflects sampling uncertainty according to its calculation method. More complex features, such as clustering or repeated measures, can require methods that account for dependence among observations; the record does not state whether such features were relevant to the primary endpoint or how they were handled.

Over-dispersion is a general concept in which observed variability exceeds what a chosen statistical model assumes. If a model underestimates variability, its uncertainty intervals may be too narrow. The registry does not identify an over-dispersion assessment or model for this study, so no claim can be made that over-dispersion occurred or that a particular correction was used.

What does the planning illustration represent?

General: A sample-size illustration asks how many participants might be needed under specified assumptions to detect an effect with a chosen power and significance level. It is a planning exercise, not a measure of the power actually achieved after a trial, and it does not establish that the observed result is true or clinically important. Estimates based on an observed effect are especially dependent on that estimate and may change under different assumptions.

The posted planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect is defined as a stated fraction of the observed effect. The record says that non-time-to-event illustrations are expressed as participants per arm for 80% or 90% power, and that time-to-event illustrations use total events. The detailed protocol justification for sample size is not reported in the registry record. As no primary observed effect is posted in the analyses, these planning assumptions should not be interpreted as a trial-specific justification or as observed power.

Overall, the statistical methods that can be described are limited to the endpoint’s stated scale, population, time frame, confidence-interval specification, and the planning assumptions. Details of the analysis model, handling of missing data, multiplicity control, and inferential testing are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: safety measures following the first vaccination and PNEUMOVAX™23, plus serotype-specific OPA geometric mean titers and IgG geometric mean concentrations at defined assessment times. It also states that there were no formal hypotheses. The record does not report a multiplicity strategy, such as a hierarchy of confirmatory outcomes or an adjustment for testing several outcomes. Without that information, the listed outcomes should be treated as separate registered measures rather than as a set of confirmatory claims with a documented family-wise error plan.

The primary outcome is described with a defined analysis population: all randomized participants who received at least 1 dose of study vaccination. The registry does not state how missing primary endpoint observations were handled, whether any participants lacked assessable follow-up, or whether a sensitivity analysis was performed. Those details are important because the interpretation of a percentage can depend on whether participants with unknown event status are excluded, counted in a particular way, or addressed through another method. No such method is reported in the registry record.

The record does not provide outcome-specific analyzed sample sizes for immunogenicity measures, missing-data summaries, or the statistical population definitions for each secondary outcome. Enrollment of 407 is not a substitute for the number contributing to every analysis. The registry also does not report interim analyses or stopping rules, and no assumptions about them can be made from the study’s completed status.

These reporting gaps limit assessment of how outcomes were prioritized, how multiple comparisons were interpreted, and how incomplete follow-up might affect the estimates. They do not establish that the study failed to address these issues in its full protocol or analysis documents; those details are simply not reported in the registry record.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea infectious (0.5%), suicidal ideation (0.5%), gastrointestinal inflammation (0.5%), hodgkin's disease (0.5%), abnormal uterine bleeding (0.5%).

The safety entries list serious adverse events and other adverse events separately for the first vaccination groups and for the groups after PNEUMOVAX™23. For serious events, the counts are 1 among 203 at risk for V114, 1 among 204 at risk for Prevnar 13™, 2 among 203 at risk for V114 (Post-PNEUMOVAX™23), and 2 among 202 at risk for Prevnar 13™ (Post-PNEUMOVAX™23). The record lists 0 deaths in each of the four groups.

These are recorded counts, not adjusted comparisons. The entries do not give confidence intervals, a statistical test, or details sufficient to determine whether the same participants contributed to more than one period. The group labels identify the vaccination context; they do not establish that an event was caused by the vaccine. The listed serious-event terms are each reported as 0.5%: Diarrhoea infectious, Suicidal ideation, Gastrointestinal inflammation, Hodgkin's disease, Abnormal uterine bleeding, and Serous retinal detachment. The record does not provide further event-level context or causal attribution for these terms.

The broader “other” adverse-event counts are not the primary endpoint. The primary endpoint is restricted to solicited injection-site events through 14 days after Vaccination 1. Because the categories and assessment periods differ, the counts should be read within their own labels rather than treated as interchangeable safety summaries.

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

The registry record establishes the study question and design: randomized assignment between V114 and Prevnar 13™ for the initial vaccination, followed by PNEUMOVAX™23 eight weeks later in both groups. It defines the primary safety endpoint as solicited injection-site events through 14 days after the first vaccination and describes additional safety and immunogenicity outcomes. This information supports understanding what the study was intended to examine.

The record does not report a numerical result for the primary endpoint. It therefore cannot establish from the posted analyses whether injection-site event percentages differed between groups, how large any difference was, or how precisely that difference was estimated. The same limitation applies to the listed immunogenicity outcomes: their titles and assessment times are present, but no analyzed values are posted. A lack of posted estimates is not evidence of no difference.

The safety record does report counts for serious and other adverse events, along with several serious-event terms. Those entries can be described as recorded counts in their respective groups and periods. They do not establish causation, provide a full account of clinical context, or show a formal comparison. The listed serious events should not be confused with the primary endpoint, which concerns a prespecified set of local symptoms after the first vaccination.

The study’s completed status and enrollment figure describe conduct and administrative status, not the strength or direction of an outcome. The record’s statement that there were no formal hypotheses also means that readers should not infer a confirmatory hypothesis test from the outcome descriptions. The protocol’s detailed statistical plan, sample-size justification, missing-data approach, and multiplicity handling are not reported in the registry record.

Accordingly, the defensible interpretation is descriptive: the registry identifies a randomized active-comparator study in children infected with HIV and documents certain safety counts, but it does not post analyses sufficient to quantify the primary comparison or the immunogenicity results. No conclusion about comparative benefit or harm follows from the design description alone.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a study’s registered question and the evidence available in its registry results. The record describes a randomized, quadruple-masked, active-comparator design, a specific primary safety endpoint, and additional immune-response outcomes. Those details make clear what investigators intended to measure and when, but they do not replace the outcome estimates needed to assess the comparison.

Statistically, the primary endpoint is a binary event summarized as a percentage. For an interpretable comparison, readers would ordinarily need the number of participants assessed, the number with a defined event in each group, and an estimate with an uncertainty measure. The registry specifies a 95% confidence interval as the endpoint’s dispersion measure, yet does not post the primary result or interval. This makes precision and comparative magnitude unavailable from the registry record.

The study also emphasizes that safety and immunogenicity are distinct domains. Local solicited events, serious adverse events, and antibody or functional immune-response measures answer different questions. A result from one category cannot stand in for another. The listed safety counts are informative as counts, but without analysis details they should not be overread as evidence of a group difference or causal effect.

The record is also a reminder that completed status and enrollment do not tell readers how many participants contributed to each endpoint or how missing observations were handled. Such information is important for judging the denominators behind percentages and the reliability of an estimate. Likewise, a planning illustration is not observed power and cannot substitute for trial-specific design documentation.

The statistical importance is therefore partly about restraint: distinguish the registered design, the safety counts that are posted, and the outcome analyses that are absent. That separation prevents a protocol description from being mistaken for a result and keeps uncertainty visible when the registry does not report the estimates needed for a comparative conclusion.

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 primary limitation for interpretation is that the registry record does not post an analysis of the primary endpoint. It gives the endpoint definition, timeframe, and analysis population, but not event counts, percentages, confidence intervals, or a comparison between V114 and Prevnar 13™. As a result, the primary safety question cannot be answered quantitatively from the posted results.

Although the record lists 9 outcome measures, it reports 0 analyses. No numerical immunogenicity results are available in the registry record, despite the listed IgG and OPA outcomes and assessment times. The registry also does not report outcome-specific denominators, missing-data handling, analysis models, or sensitivity analyses. These omissions prevent assessment of how incomplete observations may have affected estimates or how results were calculated.

The description states that there were no formal hypotheses, but does not report a multiplicity approach for the several safety and immune-response outcomes. Nor does the registry record report interim-analysis procedures or the trial’s detailed sample-size justification. The planning assumptions described for illustrations are not a substitute for the protocol’s rationale and do not establish observed power.

The adverse-event counts are limited summaries. They do not include confidence intervals or statistical comparisons, and the record does not provide event-level detail sufficient to establish causal attribution. The serious-event terms are listed with percentages but without accompanying clinical context. The “other” adverse-event category is broader than the solicited injection-site primary endpoint, so those counts cannot answer the primary question.

Finally, the population is specifically children 6 to 17 years of age inclusive infected with HIV. The record does not establish how results would generalize beyond that study population. In this case, the absence of posted endpoint analyses is the central constraint: conclusions about comparative outcomes cannot be drawn from the design and safety counts alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED) — NCT03921424.
• Registry record last updated 2023-06-07; status last verified 2023-05.
• Results first posted 2021-12-09.
• 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

NCT03921424 is a completed Phase 3, randomized, parallel-group, quadruple-masked, active-comparator-controlled study of V114 in children infected with HIV. The registry lists enrollment of 407 and describes assignment in a 1:1 ratio to V114 or Prevnar 13™, followed by PNEUMOVAX™23 eight weeks later in both groups.

The primary endpoint is the percentage with a solicited injection-site adverse event through 14 days after Vaccination 1. The registry lists additional safety and immunogenicity outcomes, states that there were no formal hypotheses, and reports 0 analyses. Serious and other adverse-event counts are posted, but no primary endpoint estimate, confidence interval, or immunogenicity result is reported in the registry record. The study began on 2019-11-05 and had a primary completion date of 2021-05-03.