Safety and Immunogenicity of V116 in Adults Living With Human Immunodeficiency Virus (HIV) (V116-007, STRIDE-7): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of V116 in Adults Living With Human Immunodeficiency Virus (HIV) (V116-007, STRIDE-7) (NCT05393037), a randomized phase 3 study. The primary outcome is Percentage of Participants With Solicited Injection-site AEs From Day 1 Through Day 5 Postvaccination in Part A.

2. Clinical Question

3. Trial Design

This was a phase 3, multicenter, randomized, double-blind, active comparator-controlled study, using a parallel-group design. The registry lists enrollment of 313 and a completed status. The recorded study dates are 2022-07-13 for the start and 2023-07-13 for primary completion. These dates describe the registry record; they do not establish the date on which results were analyzed or posted.

The principal Part A comparison was between V116 followed by placebo and PCV15 followed by PPSV23. The first regimen consisted of V116 on Day 1 and placebo on Week 8. The comparator regimen consisted of PCV15 on Day 1 and PPSV23 on Week 8. Both were described as single intramuscular doses at those visits. The primary safety endpoint covered solicited injection-site events through Day 5 after vaccination in Part A.

The record also describes a Part B for participants in the V116 + Placebo group: PCV15 was given between 10 to 18 months after V116. Part B had its own listed safety outcomes, including solicited local and systemic adverse events and vaccine-related serious adverse events. These later assessments are distinct from the primary Part A endpoint and should not be treated as part of its time window.

Immune-response outcomes were also listed. They included serotype-specific IgG geometric mean concentrations, IgG and opsonophagocytic activity geometric mean fold rises, and the percentage of participants with a >=4-fold rise in those responses. The listed comparisons covered 13 serotypes common between V116 and PCV15 + PPSV23 and 8 serotypes unique to V116. Listing an outcome does not establish that its results were reported. The registry record does not report numerical immune-response results, the randomization method, allocation concealment procedures, or the detailed statistical plan.

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: This study is conducted in two parts. Part A evaluated V116 and the comparator regimen of PCV15 followed by PPSV23. Part B evaluated PCV15 in participants who received V116 in Part A.

Part A

Reasons for not completing this period:

Part B

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who were randomized and received at least 1 dose of study intervention. Participants were included in the intervention group according to the study intervention actually received. Two participants received the incorrect study intervention that resulted in a regimen inconsistent with the 2 designated regimens planned in this study. Both participants were excluded from the safety analysis population

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 Solicited Injection-site AEs From Day 1 Through Day 5 Postvaccination in Part A, measured over Up to 5 days after each vaccination in Part A.

The primary endpoint was the percentage of participants with solicited injection-site adverse events from Day 1 through Day 5 after vaccination in Part A. The specified events were redness or erythema, swelling, and tenderness or pain. The endpoint therefore focuses on local reactions that were actively solicited during a defined period, rather than on every medical event occurring during study participation.

In general, a participant-level percentage is a way to describe how commonly an event occurred in a defined group and observation period. It can support a comparison of the frequency of solicited reactions between regimens. It does not by itself show how severe each event was, how long it lasted, or whether it was caused by vaccination. The registry definition explicitly includes events whether or not investigators considered them related to the intervention.

The endpoint description gives a 95% confidence interval as its measure of dispersion, but the registry record does not report the endpoint percentages or their confidence intervals. Nor does it specify a single reported comparison: the record indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, the endpoint definition can be described, but the posted record does not support a numerical comparison of Part A injection-site event rates.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended, in general, to make treatment groups comparable on average at the time of assignment by using a chance-based allocation process. This supports a fair comparison when the process is implemented as planned and when outcome collection and analysis are appropriate. The record identifies the study as randomized but does not report the randomization sequence method, allocation concealment procedures, or whether any stratification factors were used.

What does double-blind mean in this study?

In general, double-blinding means that two groups involved in study conduct or assessment are kept unaware of treatment assignment. This can reduce the influence of expectations on care, participant reports, and outcome assessment. The registry calls the trial double-blind, but it does not say which people were blinded, how the study maintained masking, or whether masking was assessed. The active regimens also involved different vaccines and schedules; the record does not describe the procedures used to preserve blinding across those differences.

What does the endpoint measure?

The primary endpoint is a percentage of participants with solicited injection-site events during a defined period after Part A vaccination. Such an endpoint is binary at the participant level for a particular event definition: a participant either meets the specified event criterion or does not. The listed events were redness or erythema, swelling, and tenderness or pain. The record does not provide the operational severity grades, thresholds, diary procedures, or handling of multiple local symptoms in one participant. It also does not report the outcome data needed to reproduce the percentage.

The endpoint description names a 95% confidence interval. In general, a confidence interval expresses the uncertainty associated with an estimate under a statistical method and its assumptions. An interval around a group percentage conveys the precision of that group estimate; an interval for a between-group contrast would address uncertainty in the comparison itself. The record does not report either the actual endpoint intervals or a method for calculating them. It also does not identify a primary contrast, which matters because separate intervals for each group do not, by themselves, quantify the difference between groups.

Why can adverse-event percentages be difficult to compare?

In general, observed event frequency depends on the event definition, how actively events are solicited, the observation window, and which participants contribute data. Comparisons are most interpretable when groups have comparable follow-up and outcome ascertainment. Here, the primary endpoint window is specified as up to 5 days after each vaccination in Part A. The record does not report the actual endpoint results, the amount of missing diary information, or the analysis method used for the percentage. Thus, the endpoint’s definition is available, but its estimated frequency and uncertainty are not.

The registry lists serious adverse event and other adverse event counts for Part A groups and for the V116 + Placebo group that later received PCV15 in Part B. These descriptive counts should be distinguished from a comparative model or a formal test. In general, statistical analyses of adverse events may account for different follow-up, repeated exposure, or other design features, but the record does not report such methods. It also does not report adjusted estimates, p-values, or confidence intervals for the listed counts.

What does over-dispersion mean in general?

For count data, a simple model may assume that variability follows a particular relationship to the average count. Over-dispersion means that the observed variability is greater than that assumption allows. If it is ignored, standard errors can be too small and intervals or tests may be misleading. This is a general statistical concept, not a finding about this trial: the registry record does not report a count model, an over-dispersion assessment, or an analysis of the primary endpoint using count data.

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 two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. Such calculations, in general, illustrate planning under chosen assumptions. They are not observed power and do not show that the trial was designed with those assumptions. The registry record does not report the trial’s own sample-size justification or whether these illustrative assumptions were used in its design.

Finally, the registry lists immune-response outcomes based on geometric means and fold rises. In general, geometric means are useful for measurements that are positive and can vary multiplicatively; fold rise expresses a relative change from a baseline measurement. A percentage exceeding a specified fold-rise threshold describes the proportion meeting that criterion. These are distinct summaries and do not replace the primary safety outcome. Numerical results, analysis methods, and uncertainty estimates for these immune outcomes are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and multiple secondary immune-response and Part B safety outcomes. The immune-response outcomes include several serotypes, measures of IgG and opsonophagocytic activity, and threshold-based response percentages. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can control that risk, but the record does not report whether any adjustment was planned or used, or which outcomes were intended to support formal claims.

The primary outcome itself is described as having several categories or time points and is not reduced to one comparison in the registry analysis information. The record does not specify how those categories or time points were combined, prioritized, or compared. It also does not report a hierarchy among the primary and secondary outcomes, a testing sequence, or whether any analyses were exploratory.

Missing-data handling is not reported in the registry record. In particular, the available record does not explain how participants with incomplete event diaries, missed visits, or unavailable immune-response measurements were treated. It does not report imputation methods, sensitivity analyses, or the amount of missing outcome information. Those details matter because the estimate can depend on who contributes data and how incomplete observations are handled.

The primary population is described as randomized participants who received at least 1 dose, assigned according to the intervention actually received. The record also mentions two participants who received an incorrect intervention that resulted in a regimen inconsistent with the study, but the available description does not say how they were handled in the analysis. A full account of analysis populations, exclusions, and deviations is 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: presyncope (0.8%), chest discomfort (0.6%), death (0.6%), arthritis bacterial (0.6%), neurosyphilis (0.6%).

The registry lists serious adverse event counts for V116 + Placebo (Part A) as 4 of 155, for PCV15 + PPSV23 (Part A) as 6 of 155, and for V116 + Placebo (Part A), PCV15 (Part B) as 1 of 126. The corresponding listed death counts are 1, 0, and 0. These are descriptive counts; the record does not provide a statistical comparison, confidence intervals, or an assessment of whether differences could reflect chance.

The Part B group is a later treatment context, following V116 and then PCV15, and should not be treated as another Part A randomized regimen. The registry does not report the observation duration associated with each serious-event count or clarify whether the groups had equivalent follow-up for this summary. The counts therefore do not establish comparative risk over a common period.

The record also lists serious-event terms and percentages: Presyncope at 0.8%, Chest discomfort at 0.6%, Death at 0.6%, Arthritis bacterial at 0.6%, Neurosyphilis at 0.6%, and Pneumonia at 0.6%. These entries describe reported terms, not proof that an event was caused by a vaccine. The record does not state the attribution or denominator details for these term percentages. Serious adverse events should also not be confused with the solicited injection-site events that define the primary endpoint.

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

The record establishes that the study was designed to compare vaccine regimens in adults living with HIV, with a primary focus on solicited injection-site adverse events in Part A. It describes the treatment schedules, the outcome definition, the planned follow-up window, and a population definition for the primary outcome. It also documents serious adverse event counts and lists immune-response outcomes.

Those details do not show whether the Part A groups differed in the primary endpoint. The registry record does not report the endpoint percentages, confidence intervals, or a formal comparison. It therefore does not allow readers to judge the magnitude or precision of a difference in solicited injection-site reactions. The completed status does not fill that results gap.

The serious adverse event counts provide a descriptive record of events in the listed groups, but the available information does not establish a causal relationship with an intervention or make a like-for-like comparison across groups. Follow-up context is not reported for those counts. Nor do the listed serious-event terms and percentages provide a complete account of safety or a measure of comparative treatment effect.

The study’s stated purpose included evaluating immunogenicity, and the registry lists several immune-response outcomes. However, numerical immune-response findings are not reported in the registry record. The outcome list alone cannot show how responses changed, how they compared between regimens, or how precisely they were estimated.

In general, interpreting a clinical trial requires both an estimate and information about its uncertainty, along with an understanding of the population, outcome definition, follow-up, and analysis. The available record supplies important design context but lacks the results and methods needed for a substantive assessment of comparative safety or immune response. It should not be used to claim that either regimen is better, worse, or equivalent on the outcomes listed.

13. Why This Trial Matters Statistically

This study is statistically notable because it places a defined local safety outcome alongside immune-response measures in a randomized active-comparator design for adults living with HIV. The primary endpoint is specific about the event types and the postvaccination observation period. Clear definitions are important for interpreting adverse-event percentages, since different event lists or follow-up windows can produce different summaries.

The design also includes distinct treatment contexts. Part A compares V116 followed by placebo with PCV15 followed by PPSV23, while the V116 group has a later Part B PCV15 vaccination. Keeping those contexts separate is essential when reading the adverse-event summaries: the primary endpoint concerns Part A, whereas Part B outcomes relate to later vaccination and follow-up.

From a statistical perspective, the record illustrates the difference between an outcome being specified and its results being available. A protocol-style description can identify what was measured, yet without estimates, uncertainty intervals, and analysis details, it cannot answer the comparative question. This distinction is particularly important when the record lists several outcomes and categories but does not report a single primary comparison.

The listed serious adverse event counts may be useful as descriptive context, but they cannot replace the planned primary endpoint analysis or a clearly defined comparison. Likewise, the immune-response outcome list signals the kinds of measures considered, not their observed values. The principal statistical value of the available record is therefore its account of trial design and outcome definitions; its principal limitation is the absence of reported comparative results.

14. Limitations

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

The registry record does not report numerical results for the primary endpoint, despite defining the event types, population, and observation period. It specifies a 95% confidence interval but does not provide the endpoint estimates or interval limits. The record also does not present a single reduced comparison for the primary outcome. This prevents assessment of the magnitude and precision of the planned Part A safety contrast.

Analysis details are limited. The randomization procedure, allocation concealment, masking procedures, statistical methods, and any multiplicity strategy are not reported in the registry record. Missing-data rules, outcome-specific denominators, and sensitivity analyses are also not reported. The primary population description is incomplete after noting two participants with an incorrect intervention, so their analysis handling cannot be established.

The available serious adverse event summaries do not include follow-up duration or a formal comparative analysis. The Part B group has a later treatment history, making it a different context from the Part A comparison. The registry does not provide sufficient detail to establish whether the groups’ adverse-event observation periods were comparable. The term-level serious-event percentages also lack denominator and attribution details in the available record.

Although the registry lists secondary immunogenicity outcomes, it does not report their numerical results or associated uncertainty. The stated sample-size assumptions describe a planning illustration, not the trial’s own design rationale; the registry does not report the trial’s sample-size justification. Together, these omissions limit interpretation to the study’s stated design and descriptive safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of V116 in Adults Living With Human Immunodeficiency Virus (HIV) (V116-007, STRIDE-7) — NCT05393037.
• Registry record last updated 2026-02-05; status last verified 2025-12.
• Results first posted 2024-07-25.
• 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

NCT05393037 is a completed phase 3, randomized, double-blind, parallel-group study of V116 in adults living with HIV, with PCV15 followed by PPSV23 as the Part A active comparator. The registry lists enrollment of 313 and dates from 2022-07-13 to primary completion on 2023-07-13.

The primary outcome was the percentage of participants with solicited injection-site adverse events through Day 5 after Part A vaccination. The record lists adverse-event counts and multiple immune-response and Part B safety outcomes, but it does not report numerical results or analyses for the primary comparison. The statistical methods, missing-data handling, and multiplicity plan are not reported in the registry record.