This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Immune Responses to Pneumococcal Vaccination Among HIV-infected Subjects (NCT00706550), a randomized na study. The primary outcome is Immunoglobulin G (IgG) Levels.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00706550 |
| Phase | NA |
| Condition | HIV Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 107 |
| Arms in the primary outcome | n/a |
| Lead sponsor | US Department of Veterans Affairs |
| Results posted | Yes |
2. Clinical Question
Population
HIV-infected adults with CD4 cell counts >200 who were not yet receiving combination antiretroviral treatment (ART). The study record describes vaccination timing for this population.
Intervention
Arm 1 received the 23-valent pneumococcal polysaccharide vaccine (PV) before starting ART, followed by placebo after at least 6 months of ART.
Comparator
Arm 2 received placebo before starting ART, followed by PV after at least 6 months of ART.
Primary question
The study sought to evaluate whether vaccine timing in relation to ART was associated with antibody response. Antibody levels to PV components were to be measured at 6 months and 12 months after vaccination. The registry record identifies baseline IgG levels as the primary outcome, rather than a reported post-vaccination comparison.
The central contrast is the timing sequence: vaccination before ART versus vaccination after at least 6 months of ART. Because the arms also received placebo at the other point in their sequence, the comparison concerns the assigned vaccination strategies, not simply vaccine versus no vaccine. The stated purpose was to assess whether response was better when PV was given after ART had been underway.
The registry record describes the target population and intended antibody measurements, but the posted results do not provide a single treatment-effect estimate for that question. The primary outcome is listed as baseline IgG, measured before vaccination. Baseline measurements can describe antibody levels at the start of follow-up, but by themselves do not establish how antibody levels changed after vaccination or whether those changes differed between groups.
3. Trial Design
This was a randomized, double-masked, parallel-group study sponsored by the US Department of Veterans Affairs. The registry lists enrollment of 107. The study started in 2008-10, had primary completion in 2011-09, and is marked completed. Its phase is listed as NA.
Participants were assigned by chance to one of two vaccination sequences. The immediate arm received PV before starting ART and placebo after at least 6 months of ART. The delayed arm received placebo before ART and PV after at least 6 months of ART. The record identifies the vaccine as the 23-valent pneumococcal polysaccharide vaccine. It does not describe the specific method used to generate or conceal the random allocation sequence.
In a randomized study, assignment by chance is intended to make groups comparable on average at the start, including for characteristics that may not have been measured. Masking is intended to reduce the influence of knowledge of treatment assignment on care, participant experience, or outcome assessment. The record labels the study double-masked, but does not state which roles were masked or how masking was maintained.
A parallel-group design assigns participants to separate strategies for comparison. Here, the two assigned sequences differ in when PV was administered relative to ART, while placebo was used at the other point in each sequence. The registry describes antibody measurements at 6 months and 12 months after vaccination. It does not report the detailed visit schedule, adherence information, or the analysis population used for those measurements.
The registry record does not report a detailed protocol, a statistical analysis plan, or a sample-size justification. The study is marked completed, but completion status alone does not establish that every planned measurement was collected or that every planned analysis was conducted.
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
| Stage | Immediate: PV Before Starting Antiretroviral Therapy | Delayed: PV After >6 Months of Antiretroviral Therapy |
|---|---|---|
| STARTED | 43 | 64 |
| COMPLETED | 36 | 36 |
| NOT COMPLETED | 7 | 28 |
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.
| Characteristic | Unit | Arm 1: PV Before Starting Antiretroviral Therapy | Arm 2: PV After >6 Months of Antiretroviral Therapy | Total |
|---|---|---|---|---|
| Participants analysed | 43 | 64 | 107 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 42 | 63 | 105 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 2 |
| Age, Continuous | years | 43.4 (SD 12.9) | 40.8 (SD 11.6) | 41.8 (SD 12.1) |
| Sex: Female, Male: Female | Participants | 6 | 15 | 21 |
| Sex: Female, Male: Male | Participants | 37 | 49 | 86 |
| Region of Enrollment: United States | participants | 43 | 64 | 107 |
6. Primary Endpoint
The registry lists the primary outcome as Immunoglobulin G (IgG) Levels, measured over Baseline.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Full Range |
| Unit | Micrograms/ml |
| Endpoint classification | not reduced to a single comparison |
The listed primary outcome is immunoglobulin G (IgG) levels, measured in micrograms/ml at baseline. IgG is an antibody, and the registry describes it as the most common antibody produced by the immune system. The stated reason for measuring baseline levels is to establish how much antibody participants had before vaccination, so later measurements could be considered in relation to that starting point.
The outcome is summarized as a geometric mean with full range as the dispersion measure. A geometric mean is a way of describing a central value when measurements are treated on a multiplicative scale; it is not the same as an arithmetic average. A full range describes the span from the lowest to the highest observed measurement, rather than the uncertainty around an estimated group mean. These are general interpretations of the summary measures.
Baseline IgG can help characterize participants’ starting antibody levels. To assess a vaccine response, however, post-vaccination measurements or changes from baseline must be interpreted. The study summary says antibody levels to PV components were to be measured at 6 months and 12 months after vaccination, but the posted primary outcome is listed at baseline. The registry record does not provide a single post-vaccination comparison or a treatment-effect estimate for the timing question.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record documents a randomized comparison of two vaccination sequences, but it does not provide a single comparative result for the main timing question. The primary outcome entry is baseline IgG, and the posted results do not give a treatment-effect estimate, confidence interval, or p-value for a post-vaccination comparison. The record also lists no statistical analyses. Therefore, the posted information does not establish the direction or precision of a difference in vaccine response between the assigned strategies.
Baseline antibody measurements have a descriptive role: they indicate the antibody levels participants had before vaccination. A baseline value is not itself evidence of the response produced after vaccination. The registry’s summary describes planned measurements at 6 months and 12 months after vaccination, but those time points do not appear as a single reduced comparison in the primary outcome entry. The record notes that the primary outcome has several categories or time points and is not reduced to one comparison. Without the corresponding estimates and uncertainty, it is not possible to assess whether any observed group differences are compatible with a small or substantial effect.
Random assignment supports a comparison based on assigned strategy, provided outcomes are analyzed in a way that preserves the randomized groups. The registry record does not report the analysis population, handling of participants who did not follow the assigned sequence, or adjustment methods. These omissions prevent an assessment of how the posted results, if any, relate to the original randomized comparison.
The safety information reports serious adverse events and other adverse events by arm. For serious adverse events, 6 of 43 at risk in Arm 1 and 8 of 64 at risk in Arm 2 were affected. For other adverse events, 2 of 43 at risk in Arm 1 and 1 of 64 at risk in Arm 2 were affected. These counts describe the registry’s event reporting; they do not by themselves show that assignment caused an event or establish a comparative safety effect. The record does not report deaths as group counts.
The serious-event terms listed include respiratory infection at 7.0%, mental health related at 4.7%, death at 3.1%, gastrointestinal infections and other disorders at 3.1%, CHF, arrhythmia at 2.3%, and other infections at 2.3%. The registry does not clarify the denominator or whether these categories can overlap. These percentages should therefore be read as reported term frequencies, not as a complete account of individual risk or a comparison between the randomized strategies.
Overall, the posted information describes the study design, an intended antibody assessment, and adverse-event counts, but does not provide enough outcome detail to quantify the vaccine-timing effect. The absence of a reported comparative estimate is not evidence that the strategies had identical results.
9. Statistical Methods Explained
The study is described as randomized, double-masked, and parallel-group. These labels describe design features, not the results. Randomization assigns participants by chance, which is intended to reduce systematic differences between groups at the outset. It does not guarantee that every characteristic will be balanced in a particular study. The record does not describe the random sequence method, allocation concealment, or the characteristics of the randomized groups.
What does masking contribute?
Masking means that some people involved in a trial are not told which treatment was assigned. In general, this can limit the influence of expectations on behavior, care, or assessment. The registry labels this study double-masked, but does not specify who was masked or whether the masking remained intact. The use of placebo in each assigned sequence is part of the described design; further details about its appearance or administration are not reported in the registry record.
What is the comparison?
The comparison is between assigned vaccination sequences: PV before ART, with placebo after at least 6 months of ART, and placebo before ART, with PV after at least 6 months of ART. The study’s stated purpose was to evaluate vaccine timing in relation to ART. A comparison of the assigned strategies is conceptually different from comparing participants who actually received vaccine at different times, because actual treatment receipt or adherence may not match assignment. The registry record does not report adherence or deviations from the assigned sequence.
How should the outcome summary be read?
The primary outcome is IgG levels at baseline, expressed as a geometric mean in micrograms/ml, with full range as dispersion. In general, a geometric mean summarizes measurements on a multiplicative scale and can be useful when values vary proportionally rather than additively. The full range reports the observed span; it does not quantify the precision of a group estimate. A confidence interval, when reported, conveys a range of values compatible with the data and model at a stated confidence level. No confidence interval for a treatment comparison is reported in the registry record.
Baseline values describe starting antibody levels. They cannot, alone, quantify a response to vaccination. The summary states that antibody levels to PV components were to be measured at 6 months and 12 months after vaccination. Interpreting those measurements would require the relevant group estimates and a defined comparison, such as a post-vaccination contrast or change from baseline. The registry record does not report one consolidated estimate for that question.
Why can the analysis choice matter?
In general, an analysis should match the study question and the way the outcome was collected. For repeated measurements, an analysis may need to account for measurements from the same participant being related to one another. If the outcome includes multiple antibody components or time points, the analysis must also clarify which contrasts are primary and how uncertainty is handled across them. The registry record does not report a statistical analysis plan or the methods used for these issues.
For outcomes summarized as counts, such as adverse events, interpretation depends on the definitions, observation period, and population at risk. The registry provides group counts at risk and counts affected for serious and other adverse events. It does not describe event-collection procedures, follow-up duration for safety, or whether the reported events were judged related to treatment. General statistical practice distinguishes a count of people with at least one event from a count of all event occurrences; the record’s wording does not provide enough detail to resolve that distinction for every listed term.
What can the posted statistical information establish?
The registry lists no statistical analyses and does not report a comparative estimate, uncertainty interval, or p-value for the vaccine-timing question. A p-value, in general, describes how unusual data at least as extreme as those observed would be under a specified null model; it is not a measure of effect size or clinical importance. A confidence interval gives information about the uncertainty and range of estimates compatible with a model, but neither is available for the primary comparison in the registry record.
The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration considers effects expressed as stated fractions of the observed effect; time-to-event planning is described in total events, while other planning is described in participants per arm. Such figures are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry record does not report the trial’s own sample-size justification.
Because no consolidated comparison or analysis methods are posted, the design labels alone cannot establish the size, precision, or statistical significance of an effect. The result must be interpreted as an incomplete record of the intended comparison rather than as a quantified estimate of the difference between strategies.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies six outcome measures, and the primary outcome entry concerns baseline IgG. The study summary also describes antibody measurements at 6 months and 12 months after vaccination, while the record notes that the primary outcome has several categories or time points and is not reduced to one comparison. When a study evaluates multiple outcomes, antibody components, or time points, there can be multiple opportunities to observe a difference. General statistical methods may account for this multiplicity or identify a prespecified primary contrast, but the registry record does not report a multiplicity strategy or a detailed statistical analysis plan.
Missing-data handling is also not reported in the registry record. The posted information does not describe how participants without a baseline or follow-up measurement were handled, whether follow-up differed between arms, or whether any missing values were imputed. These details matter because estimates based only on participants with recorded outcomes can be affected if missingness is related to treatment assignment or outcome values. This is a general concern, not evidence that missing data occurred in this study.
The record does not identify an analysis population, such as all randomized participants or participants who completed the assigned sequence. It also does not report how protocol deviations or treatment discontinuation were handled. Without that information, it is not possible to determine whether a reported estimate would represent the effect of assignment or an analysis restricted to a selected group. No such comparative estimate is posted.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm 1: PV Before Starting Antiretroviral Therapy | 6 | 43 | 14.0% |
| Arm 2: PV After >6 Months of Antiretroviral Therapy | 8 | 64 | 12.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1: PV Before Starting Antiretroviral Therapy | 2 of 43 |
| Arm 2: PV After >6 Months of Antiretroviral Therapy | 1 of 64 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1: PV Before Starting Antiretroviral Therapy | Arm 2: PV After >6 Months of Antiretroviral Therapy |
|---|---|---|---|
| Respiratory infection | Respiratory, thoracic and mediastinal disorders | 3 of 43 | 4 of 64 |
| Death | General disorders | 1 of 43 | 2 of 64 |
| CHF, arrhythmia | Cardiac disorders | 1 of 43 | 1 of 64 |
| Gastrointestinal infections and other disorders | Gastrointestinal disorders | 0 of 43 | 2 of 64 |
| Mental health related | Psychiatric disorders | 2 of 43 | 0 of 64 |
| Other infections | Infections and infestations | 1 of 43 | 1 of 64 |
| Skin infection | Skin and subcutaneous tissue disorders | 1 of 43 | 1 of 64 |
| Cerebrovascular accident | Nervous system disorders | 0 of 43 | 1 of 64 |
| Dehydration, electrolite abnormalities | General disorders | 0 of 43 | 1 of 64 |
| Elective surgery | Surgical and medical procedures | 0 of 43 | 1 of 64 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1: PV Before Starting Antiretroviral Therapy | Arm 2: PV After >6 Months of Antiretroviral Therapy |
|---|---|---|---|
| Upper respiratory infection | Infections and infestations | 1 of 43 | 1 of 64 |
| Anemia | Blood and lymphatic system disorders | 1 of 43 | 0 of 64 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 43 | 1 of 64 |
Serious events with the highest arm-level rate: respiratory infection (7.0%), mental health related (4.7%), death (3.1%), gastrointestinal infections and other disorders (3.1%), chf, arrhythmia (2.3%).
The registry reports serious adverse-event counts by arm. In Arm 1, 6 of 43 participants at risk were affected; in Arm 2, 8 of 64 participants at risk were affected. For other adverse events, the corresponding entries are 2 of 43 and 1 of 64. These are counts from the registry record, not adjusted comparisons. No calculation of a difference or relative risk is reported.
The listed serious-event terms and percentages are respiratory infection, 7.0%; mental health related, 4.7%; death, 3.1%; gastrointestinal infections and other disorders, 3.1%; CHF, arrhythmia, 2.3%; and other infections, 2.3%. The registry does not state the denominator used for these percentages or clarify whether one participant could contribute to more than one term. They should not be treated as mutually exclusive categories unless the record establishes that.
The group-level death count is listed as null, so deaths by arm are not reported in the registry record. The appearance of “Death” among serious-event terms is a separate registry entry and does not supply a group-specific death count. The record also does not report whether events were considered related to PV, placebo, or ART, or provide a comparative safety analysis. Event counts alone cannot establish causation.
12. What the Result Does, and Does Not, Mean
This trial was designed to examine the timing of pneumococcal vaccination in relation to ART among HIV-infected adults with CD4 cell counts >200 who were not yet receiving combination ART. Random assignment and double masking are relevant design features for making a comparison between the assigned strategies. The two arms differed in whether PV was given before ART or after at least 6 months of ART, with placebo used at the other point in the sequence.
The registry record does not provide a single comparative estimate for antibody response. It lists baseline IgG as the primary outcome and describes planned antibody measurements at 6 months and 12 months after vaccination, but does not post a treatment-effect estimate, confidence interval, or p-value for the timing comparison. Consequently, the available record does not show how large a difference in response was observed, how precisely it was estimated, or whether the two strategies produced similar or different outcomes.
This lack of a reported comparison should not be interpreted as proof that there was no effect. It means the registry record does not provide the information needed to quantify the effect. Likewise, the study’s completion status does not establish that every planned endpoint was collected or analyzed.
The adverse-event counts provide a descriptive safety account, but do not establish that vaccination timing caused or prevented events. Group counts, serious-event terms, and percentages are not a substitute for a defined comparative analysis with clear denominators and follow-up. The registry record does not report a causal attribution assessment or a group-specific death count.
In general, a trial’s design can be informative even when its posted results are incomplete: it identifies the intended population, strategies, and outcomes. For conclusions about the comparative antibody response, however, readers would need the post-vaccination results, their uncertainty, and details of the analysis. Those are not reported in the registry record.
13. Why This Trial Matters Statistically
The study addresses a statistical comparison in which timing is part of the intervention strategy. The question is not simply whether PV was given, but whether receiving it before ART or after at least 6 months of ART was associated with a different antibody response. Designing the arms as sequences with placebo at the other point helps define the intended contrast in the registry description.
Randomization and masking are important because they can reduce some sources of bias in comparisons. Random assignment is intended to balance measured and unmeasured characteristics on average, while masking can limit the influence of treatment knowledge. Those features strengthen a study’s design, but they do not replace reporting the outcome estimates, uncertainty, and analysis choices needed to interpret the results.
The endpoint also illustrates why outcome timing matters. Baseline IgG levels describe the starting point; the study’s stated interest concerns antibody levels after vaccination. A clear statistical report would connect the repeated measurements and the assigned strategies through an explicit comparison. The registry record does not provide that consolidated comparison, which limits what can be learned about the magnitude and precision of the result from the posted information.
Finally, reporting the safety denominators and event counts is useful for understanding what the registry records, but counts require context. Follow-up definitions, event overlap, and attribution affect interpretation. This trial therefore highlights a general principle: a well-defined clinical question and design are only part of the evidence. Results need transparent endpoint definitions and analysis reporting to support a precise interpretation.
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 principal limitation of the posted record for interpreting the study question is the lack of a comparative post-vaccination antibody estimate. Although the registry summary describes measurements at 6 months and 12 months after vaccination, the primary outcome entry is baseline IgG. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. It does not report a treatment-effect estimate, confidence interval, or p-value for the timing question.
The statistical analysis plan is not reported in the registry record. The record does not describe the planned primary contrast, how repeated measurements or multiple antibody components were handled, or whether analyses adjusted for baseline levels. These are possible analysis considerations, not claims that a particular method was required or used.
The analysis population, missing-data approach, and handling of deviations from assigned treatment are also not reported. It is therefore not possible to assess whether the outcome data were analyzed according to randomized assignment or another population definition. The record does not provide detailed participant flow or follow-up completeness for the antibody measurements.
For safety, the record gives group counts and serious-event term percentages but does not explain the percentage denominators, whether event categories overlap, the safety follow-up period, or whether events were attributed to a study treatment. Death counts by group are not reported in the registry record. These reporting gaps limit comparative interpretation and do not establish that any specific event was caused by vaccination.
The record lists enrollment of 107 and describes a planning illustration based on the observed effect, but does not report the trial’s own sample-size justification. The illustration should not be treated as observed power or as a substitute for the missing outcome estimates. These limitations concern the information available in the registry record; they do not establish what may be reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immune Responses to Pneumococcal Vaccination Among HIV-infected Subjects — NCT00706550.
- Registry record last updated 2014-04-24; status last verified 2014-03.
- Results first posted 2013-12-12.
- 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.
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18. Record Summary
NCT00706550 is a completed, randomized, double-masked, parallel-group study sponsored by the US Department of Veterans Affairs. The registry lists enrollment of 107, a start date of 2008-10, and primary completion in 2011-09. The study enrolled HIV-infected adults with CD4 cell counts >200 who were not yet receiving combination ART, according to its summary.
The assigned strategies compared PV before ART with PV after at least 6 months of ART; placebo was used at the other point in each sequence. The primary outcome is listed as baseline IgG levels in micrograms/ml, summarized by geometric mean with full range. The study summary describes antibody measurements at 6 months and 12 months after vaccination.
The registry record lists six outcome measures and no statistical analyses. It does not report a single comparative estimate for the antibody-response question, nor a group-specific death count. Serious and other adverse-event counts are reported by arm, with additional serious-event terms and percentages whose denominators are not specified.