Human Papillomavirus Vaccine Therapy in Treating Men With HIV-1 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Human Papillomavirus Vaccine Therapy in Treating Men With HIV-1 Infection (NCT00513526), a na phase 2 study. The primary outcome is Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine.

2. Clinical Question

The study was a phase II pilot focused on safety and immunogenicity in men with HIV-1 infection. Its primary question concerns a vaccine-related safety outcome, rather than a comparison of vaccine with placebo or another treatment. The registry also lists outcomes involving CD4+ cell counts, plasma HIV-1 RNA, HPV antibody titers to types 6, 11, 16, and 18, and oral serum IgA levels.

Because this is a single-group study, its results can describe outcomes observed among participants receiving the vaccine under the study conditions. They cannot, by themselves, distinguish vaccine effects from changes that might have occurred without vaccination or under another treatment. The registry record does not report a primary endpoint estimate, so the frequency of the specified primary outcome cannot be evaluated from the stated results. The record also does not report a comparator-based estimate of vaccine effect.

3. Trial Design

This was a phase II, single-arm, open-label pilot trial of the safety and immunogenicity of quadrivalent HPV vaccine in HIV-1-infected men. The registry records an enrollment of 112 and lists the study as completed. The recorded start was 2007-11, and primary completion was 2010-05. Allocation was not applicable to the single-group design, and masking was none.

Participants received Gardasil by intramuscular injection at study entry, week 8, week 24, and week 128. The vaccine contained HPV types 6, 11, 16, and 18. The primary outcome was the occurrence of grade 3 or higher adverse events judged probably or definitely related to the vaccine, assessed across all study visits. The registry defines the primary endpoint population as participants who received at least one vaccine dose.

The registry lists secondary outcomes covering longitudinal changes in CD4+ cell count and plasma HIV-1 RNA, HPV antibody titers by type and baseline seropositive status, and oral serum IgA before and after the vaccination series. These outcomes describe a broader set of safety and immune-response questions, but the registry record does not report results for them in the registry record for this analysis.

The design is important for interpretation: an open-label, single-group study can provide descriptive observations about participants’ outcomes, but it has no concurrent control group for separating treatment-associated changes from other influences. The record does not report a detailed statistical analysis plan, a sample-size justification, or information about interim analyses. The posted sample-size material is described as a planning illustration based on an observed effect, not as the trial’s original design calculation or observed power.

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

Analysis population for the primary outcome, as defined in the registry: Intention to treat (i.e., received at least one dose of the vaccine)

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 Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine, measured over All study visits.

The primary endpoint counts participants with grade 3 or higher adverse events considered probably or definitely related to the vaccine. Its timeframe is all study visits, and the registry specifies a 95% confidence interval as the measure of uncertainty. This endpoint is intended to characterize the occurrence of more severe events that investigators considered to have a likely relationship to vaccination. It is a safety measure, not a measure of immune response or a comparison of clinical benefit.

Counting participants with an event makes the outcome interpretable as a binary result: a participant either meets the endpoint definition or does not. A confidence interval expresses uncertainty around an estimated event frequency; it does not guarantee that the true frequency lies within the interval. The registry record does not report the primary endpoint estimate or its confidence interval in the registry record for this analysis. Therefore, the endpoint definition and planned uncertainty measure can be described, but the primary event frequency and its precision cannot be assessed.

The endpoint is also distinct from the serious adverse event figures. The primary definition is based on severity grade and the investigator’s assessment that the event was probably or definitely related to vaccine. Seriousness and severity grading are not interchangeable concepts, and the registry’s serious-event summary does not establish that those events met the primary endpoint definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting this study requires separating its design, endpoint definition, and available results. The trial is single-group and open label, with no randomized comparator. Its primary safety endpoint is defined as the occurrence of grade 3 or higher adverse events considered probably or definitely related to the vaccine across all study visits. The registry specifies a 95% confidence interval for this endpoint, but the endpoint estimate and interval are not reported in the registry record for this analysis.

What does a single-group design allow?

A single-group design follows participants receiving the intervention and describes what happens during follow-up. It can document events and immune measurements in the enrolled study population. Without a concurrent control group, it cannot directly estimate what would have happened to similar participants under another treatment or without vaccination. Differences over time may reflect the intervention, changes in participants’ health, measurement variation, or other influences. Open-label status means masking was none; the record does not report additional procedures intended to reduce the potential influence of knowledge of treatment assignment.

What does the primary endpoint count?

The endpoint is binary at the participant level: the relevant question is whether a participant experienced an event that met the specified severity and relationship criteria. A count of participants with an event is different from a count of all event episodes, since one participant could potentially experience more than one event. The registry record does not provide enough detail to determine how repeated events were handled in the primary analysis. Nor does it report the primary count, the denominator used for that estimate, or its confidence interval.

The relationship criterion is also part of the definition. Events considered probably or definitely related to vaccine form the primary endpoint, whereas the serious adverse event summary is a separate safety classification. Seriousness, severity grade, and assessed relationship to treatment describe different aspects of an event. A serious event is not automatically grade 3 or higher, and the available record does not say that every serious event was judged probably or definitely related to the vaccine.

How should a confidence interval be understood?

In general, a confidence interval communicates the precision of an estimated quantity under the assumptions of its statistical method. A narrower interval indicates greater precision than a wider interval, while neither width nor coverage establishes causation. A confidence interval around a single-group event frequency would describe uncertainty in that frequency, not uncertainty in a comparison with an untreated group. Here, the registry specifies a 95% confidence interval for the primary endpoint but does not report the interval itself, so its precision cannot be assessed.

What do the planning illustrations mean?

The sample-size illustrations are described as planning calculations based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. They are not the trial’s own design justification and are not observed power. The stated effect to detect is a fraction of the observed effect. For a binary outcome, an unadjusted planning calculation can illustrate how the required participants per arm would vary with the target effect and design assumptions. Such an illustration does not validate the original single-group study, and a hypothetical two-arm calculation does not create a comparator that the trial did not have. No specific planning values are available in the registry record for this analysis.

More generally, planning calculations depend on the assumed event frequency, target effect, significance level, power, allocation, and analysis method. If those assumptions differ from the eventual study conditions, the calculation may not describe the study’s actual precision. The registry record does not report the trial’s sample-size justification or a statistical plan, so it is not possible to establish how enrollment was selected or whether the planning illustrations match the original protocol.

What can be inferred from the safety summaries?

The registry safety summary gives 5 affected among 109 at risk for serious adverse events and 56 affected among 109 at risk for other adverse events. These are reported counts and denominators, not a randomized treatment contrast. The record also lists five serious-event terms with a frequency of 0.9% each. These percentages should be read as reported, rather than recalculated or added. They do not establish how many people experienced events, whether terms overlap, or whether the events met the primary endpoint’s relationship and severity criteria.

Statistical interpretation depends on the analysis denominator and event definition. The primary endpoint population is defined as intention to treat, meaning receipt of at least one vaccine dose, while the safety summary reports its own at-risk denominators. The registry record does not explain the relationship between these populations or give the primary endpoint’s analyzed denominator. Thus the adverse-event summaries should not be substituted for the primary endpoint estimate.

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("Gardasil")
n      <- c(109)
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  Gardasil  109  0  0.0  0.0  3.3  0.0  3.4  0.0  3.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary safety outcome and secondary measures involving CD4+ cell count, plasma HIV-1 RNA, HPV antibody titers, and oral serum IgA. When a study evaluates multiple outcomes, the chance of finding an apparently unusual result across the collection of tests can increase. Statistical approaches such as prespecifying a primary outcome or adjusting for multiple comparisons can address particular concerns, but the registry record does not report whether any multiplicity adjustment was planned or used. The existence of a named primary endpoint does not, by itself, establish how secondary outcomes were handled.

The registry lists zero analysis entries. That does not prove that no statistical analyses occurred; it means analysis records are not reported in the registry entries available for this account. The record does not report detailed analysis methods for the secondary outcomes, model specifications, or procedures for handling repeated measurements.

The primary population is described as intention to treat, defined as participants who received at least one vaccine dose. This is the registry’s stated definition; it differs from definitions that might include all enrolled participants, and no alternative analysis population is reported. Safety summaries use denominators of 109 at risk, while enrollment is 112. The registry entries do not explain this distinction, so these figures should not be reconciled by assumption.

Missing-data methods, the amount and pattern of missing data, and any imputation procedures are not reported in the registry record. The record also does not state whether participants who discontinued follow-up were handled in a particular way. Without these details, the possible effect of incomplete outcome data on estimates cannot be assessed. No sample-size justification or interim analysis plan is reported either.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatobiliary/pancreas - other (specify, __) (0.9%), pain / head/headache (0.9%), pain (0.9%), musculoskeletal/soft tissue - other (specifiy, __) (0.9%), infection with normal anc or grade 1 or 2 neutrophils/bone (osteomyelitis) (0.9%).

The serious adverse event summary lists 5 affected among 109 at risk in the Gardasil group. The summary for other adverse events lists 56 affected among 109 at risk. The registry also lists serious-event terms with a reported frequency of 0.9% each, including hepatobiliary/pancreas, headache, pain, musculoskeletal/soft tissue, and osteomyelitis terms. These are descriptive safety figures; they are not a comparison with a control group.

The serious-event figures should not be treated as the primary endpoint result. The primary endpoint requires grade 3 or higher events considered probably or definitely related to the vaccine. The serious-event summary does not, in the registry entries, establish severity grade or relationship to vaccination for each event. The record also does not clarify whether the affected counts refer to participants with at least one event or another counting convention, nor whether serious-event terms overlap. The listed percentages therefore should not be added or used to infer a count of distinct participants.

Enrollment was 112, whereas the safety summaries use 109 at risk. The reason for this difference is not reported in the registry record. It is also not reported whether the serious events were independently reviewed or how event terms were coded. These omissions limit interpretation of the safety counts and prevent direct reconstruction of the primary endpoint.

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

The study’s stated purpose was to examine safety and immunogenicity of quadrivalent HPV vaccine in men with HIV-1 infection. The registry describes the vaccine schedule and defines a primary safety endpoint focused on grade 3 or higher events considered probably or definitely related to vaccine. The available safety summaries report counts for serious and other adverse events, while the registry lists serious-event terms with frequencies of 0.9% each.

Those observations describe events recorded in the vaccine group. They do not establish that vaccination caused the events, because the trial had no concurrent comparison group. They also do not show whether event frequency was higher or lower than it would have been without vaccination. The primary endpoint result itself is not reported in the registry entries available for this analysis, so its frequency and statistical precision cannot be stated.

The study also lists immune and clinical measurements, including HPV antibody titers, CD4+ cell count, plasma HIV-1 RNA, and oral serum IgA. The registry record does not report results for these measures in the registry record, so no conclusion about changes in those outcomes is warranted.

The record does not establish that the intervention does or does not work. Rather, it documents a pilot, open-label, single-group investigation and some descriptive safety summaries. The results cannot be interpreted as a controlled estimate of treatment effect. The registry’s missing primary endpoint estimate, unspecified handling of missing data, and lack of reported multiplicity procedures further constrain what can be concluded from the record. The findings are best understood as limited descriptive evidence, not as a definitive comparison or a guarantee about safety.

14. Why This Trial Matters Statistically

This trial is statistically informative because its design makes the distinction between describing outcomes and estimating a treatment effect especially important. A single-group study can record safety events and immune measurements over time, but it cannot supply a randomized comparison with another treatment or no vaccination. The distinction matters when interpreting events that occurred during follow-up: temporal occurrence alone does not establish that the vaccine caused an event.

The primary endpoint combines a severity threshold with an assessment of relationship to vaccine. These features make its definition more specific than an all-event count, but interpretation still depends on how events were graded and attributed, how repeated events were counted, and which participants were included in analysis. The registry record defines the primary population as participants who received at least one dose but does not report the primary endpoint estimate or detailed analysis procedures.

The record also illustrates why safety summaries need careful reading. The serious-event figures and other-event figures are not interchangeable with the primary endpoint, and the listed serious-event terms do not establish that each met the primary endpoint criteria. Enrollment and safety denominators differ, with no explanation reported in the record.

Finally, multiple secondary outcomes create questions about analysis and interpretation. The record lists a range of immune and clinical measures but does not report their results or any multiplicity approach. The planning illustrations are explicitly not the trial’s original design calculation or observed power. Together, these details show why a pilot study can contribute descriptive information while leaving substantial uncertainty about comparative effects, precision, and the general meaning of observed events.

15. Limitations

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

The central limitation is the single-group, open-label design. With no concurrent comparator, the trial cannot estimate a randomized difference in safety outcomes or separate vaccine-associated events from background events and other influences. Open-label status also means treatment assignment was not masked, although the registry does not report how that may have affected event assessment.

The available the registry entries do not include the primary endpoint estimate or its 95% confidence interval. The serious adverse event summary cannot fill that gap because its event definition is not shown to match the primary endpoint’s grade and relatedness criteria. The record does not explain whether the safety counts are participants with events or another event-counting unit, whether event terms overlap, or how repeated events were handled.

Enrollment was 112, while the safety summaries report 109 at risk. The reason for the difference is not reported in the registry record. Although the primary endpoint population is defined as participants who received at least one dose, the record does not state the primary endpoint denominator or explain whether it matches the safety summary population.

The record does not report missing-data methods, detailed statistical models, multiplicity procedures, a sample-size justification, or an interim-analysis plan. It lists secondary outcomes but does not provide results for them in the registry record for this analysis. These limitations restrict assessment of precision, potential bias, and the robustness of any pattern across outcomes. The study’s pilot status and lack of control group further limit how broadly its descriptive findings can be interpreted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Human Papillomavirus Vaccine Therapy in Treating Men With HIV-1 Infection — NCT00513526.
• Registry record last updated 2023-11-14; status last verified 2023-10.
• Results first posted 2011-07-26.
• 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 phase II trial studied quadrivalent HPV vaccine in men with HIV-1 infection. It was a single-arm, open-label pilot with enrollment of 112 and vaccine injections scheduled at study entry and weeks 8, 24, and 128. The primary endpoint concerned grade 3 or higher adverse events considered probably or definitely related to vaccine across all study visits, in participants who received at least one dose.

The registry reports safety summaries of 5 affected among 109 at risk for serious adverse events and 56 among 109 at risk for other adverse events. It does not report the primary endpoint estimate or confidence interval in the registry record for this analysis. There was no concurrent control group, and results for the listed secondary immune and clinical outcomes are not reported in the available record. Missing-data handling, multiplicity procedures, and a detailed statistical analysis plan are also not reported.