HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease (NCT01141205), a randomized phase 1 study. The primary outcome is Tolerability and Safety of the Treatment..

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group Phase I study of AFO-18 and saline. Its official title identifies it as a Phase I study of HIV-1 peptide immunisation in individuals in West Africa. The registry lists Statens Serum Institut as sponsor and describes the study as completed. The recorded study start is 2009-08, and primary completion is recorded as 2012-06.

The brief description frames the study as therapeutic immunisation in untreated, healthy individuals with chronic HIV-1 infection. AFO-18 consisted of 18 peptides representing CD8 and CD4 epitopes, mainly on HIV-1, with the adjuvant CAF01. Saline was the placebo control. The registry describes random allocation and a single mask, but does not specify who was masked, how allocation was generated or concealed, or how masking was maintained.

The primary purpose was evaluation of tolerability and safety. The registry identifies the primary measure as the number of participants with vaccine-related degree 3 or 4 adverse events, with follow-up described as up to 6 months after the end of treatment. The brief description also identifies secondary aims related to immune response, viral load, CD4 T-cell counts, and feasibility of research in a poorly resourced African setting. Three secondary outcomes are listed in the record.

The brief description says the study was designed for 20 fully evaluable HIV-1-infected patients, with 15 vaccine-treated and 5 saline-treated controls. Separately, registry enrollment is listed as 18. The posted primary outcome arms are reported as Vaccinee with 16 participants and Placebo with 4 participants. Adverse-event risk groups have their own reported denominators, which are not the same as the primary outcome arm counts. These figures describe different registry entries and should not be silently combined or treated as interchangeable.

The registry does not report the detailed protocol, sample-size justification, randomisation procedure, or a prespecified statistical analysis plan. The planning illustrations described with the results are not the study's own design calculations.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analyzed: number of participants started minus individuals lost to follow up or participants that withdraw. Thus we include the two individuals where the physician stopped his/her participation because of SAE not related to the vaccine or to the placebo. Reported: numbers of participants with vaccina related SAE

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 Tolerability and Safety of the Treatment., measured over up to 6 months after end of treatment.

The primary endpoint is the number of participants with vaccine-related adverse events of degree 3 or 4. The registry gives a timeframe of up to 6 months after the end of treatment and describes the measure in terms of participants, rather than the number of events. It therefore records whether participants experienced at least one event meeting the endpoint definition, not how many separate qualifying events each participant had.

Severity and attribution are both part of the endpoint. The event must be classified as degree 3 or 4 and considered related to the vaccine. This is narrower than counting every adverse event, every serious adverse event, or every event occurring during follow-up. The registry does not give a fuller grading scale or detailed criteria for judging vaccine relationship in the posted description.

Safety and tolerability are the stated primary purpose, making this endpoint relevant to the early evaluation of an intervention. In general, counting participants with specified adverse events can provide a direct description of how often the defined safety outcome occurred in the study groups. It does not, on its own, establish the cause of every event or describe the range and timing of all adverse experiences.

The posted value is zero in the Vaccinee arm and zero in the Placebo arm. The record also states a safety goal framed around treatment-related degree 3 or 4 side effects among vaccine-treated participants. The endpoint results should be read according to their stated definition: they do not mean that no adverse events of any kind occurred.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either had a vaccine-related degree 3 or 4 adverse event during the specified follow-up or did not. The posted summaries report the number of participants with the event, rather than a continuous measurement such as a laboratory value. For this outcome, the record gives a value of zero in both the Vaccinee and Placebo arms.

What does a zero event count mean?

A zero is the observed count, not proof that the event cannot occur. In general, a confidence interval expresses uncertainty around an estimate and indicates the range of values reasonably compatible with the observed data under the method used. The registry record does not report a confidence interval for this endpoint. With no interval, readers cannot use the posted primary result to judge a formal range of plausible event frequencies from this record alone. A zero count also gives no information about less severe events that do not meet the endpoint definition.

Comparisons of binary outcomes can be expressed in several ways, such as a difference in event proportions or a relative measure. These measures answer different questions and their usefulness depends on event counts and denominators. In this case, a two-arm binary comparison is marked as missing or not estimable, and no recalculated comparison is reported. No comparative effect estimate should be inferred from the matching zero counts.

Why do the denominators matter?

The registry reports several populations for different purposes. Enrollment is listed as 18. The primary outcome arms report 16 participants in the Vaccinee group and 4 in the Placebo group. The serious-adverse-event risk groups report 18 at risk for AFO-18 and 5 at risk for Saline. These are not interchangeable denominators. The primary outcome description defines an analyzed population using participants who started, excluding those lost to follow-up or who withdrew, and notes that it includes two individuals whose physicians stopped their participation because of a serious adverse event considered unrelated to vaccine or placebo. The record does not fully reconcile the various population counts. Interpretation should preserve each denominator as reported rather than use one group's denominator for another outcome.

General statistical practice distinguishes the number randomized, the number who started treatment, the number followed, and the number analyzed. Missing outcome data can affect an estimate if those without observed outcomes differ from those with data. The record's brief analysis-population description does not give complete participant flow or a detailed account of missing outcome values. The extent and handling of missingness beyond that description are not reported in the registry record.

How should the planning illustrations be read?

The planning illustrations are described as calculations based on the observed effect, using equal allocation between arms, a two-sided significance level of 0.05, and a normal approximation. They consider detection of a stated fraction of the observed effect and report participants per arm for 80% power or other stated planning levels, rather than observed study results. The available record does not give the numerical planning values in the registry record described for this analysis. More importantly, the registry labels these calculations as planning illustrations, not as the trial's design calculations. They are not observed power and do not show that the study had a particular chance of detecting an effect after its results were known.

General power calculations estimate the sample size needed under chosen assumptions about the effect, variability, allocation, and statistical threshold. The result depends on those assumptions; changing them can change the planning estimate. A calculation based on an observed effect is especially not a substitute for the prospective sample-size justification, which is not reported in the registry record. No sample-size assumptions should be attributed to the original protocol based on these retrospective illustrations.

What does the record say about analysis?

The registry lists four outcome measures and three secondary outcomes, but lists zero analyses. The listed secondary outcomes concern induction of new T-cell immune response, lowering HIV-1 RNA viral load among immune responders, and increase in blood CD4 T-cell counts. Their names identify the intended measures, but they do not provide comparative estimates or uncertainty. Detailed statistical methods, adjustment procedures, interim analyses, and a prespecified analysis plan are not reported in the registry record.

For safety outcomes, counts should be interpreted alongside event definitions, attribution, follow-up, and denominators. General statistical reasoning also cautions that serious events and endpoint-defined treatment-related events answer different questions. The record lists serious events in separate adverse-event entries; it does not establish a direct mapping between those entries and the primary endpoint. Thus, the primary zero counts and the serious-event counts can both be reported without treating either as a correction of the other.

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("Vaccinee", "Placebo")
n      <- c(16, 4)
events <- c(0, 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  Vaccinee  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5
ARM  Placebo  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three secondary outcomes: induction of a new T-cell immune response, lowering of HIV-1 RNA viral load among immune responders, and an increase in blood CD4 T-cell counts. These outcomes correspond to distinct questions, and multiple outcome testing can increase the chance of finding an apparently notable result by chance when many hypotheses are examined. General methods for addressing multiplicity include defining a primary comparison in advance or adjusting inference across a family of tests. The registry record does not report a multiplicity strategy, and it lists zero analyses. The secondary outcome names should therefore not be treated as evidence that the outcomes were achieved or that statistical tests were conducted.

The primary outcome description defines the analyzed population as participants who started, minus individuals lost to follow-up or participants who withdrew. It also says that two individuals whose physicians stopped participation because of serious adverse events not related to vaccine or placebo are included. The record does not provide a complete participant flow or a detailed account of outcome availability and missing-data handling. How missing outcomes were treated beyond the stated population definition is not reported in the registry record.

Enrollment is listed as 18, whereas the primary outcome arms and adverse-event risk groups report other denominators for their respective analyses. The record does not fully explain these differences. Keeping the denominators attached to their specific outcomes is essential; they should not be combined into a new total or assumed to represent the same analysis population.

The registry does not report an interim analysis plan, imputation method, sensitivity analysis for missing data, or detailed statistical analysis plan. The posted outcomes support a descriptive account of the recorded counts, but not an assessment of how all potential missingness or multiple testing was handled.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: increase in liver enzymes (20.0%), died of pneumonia (5.6%).

The primary safety result counts participants with vaccine-related degree 3 or 4 adverse events. The registry reports zero in the Vaccinee arm and zero in the Placebo arm. This is not a count of all adverse events, and the event must meet both the stated severity and relationship criteria to qualify for this endpoint.

The separate serious-adverse-event entries report 1 affected participant among 18 at risk in the AFO-18 group and 1 among 5 at risk in the Saline group. The registry also lists 0 participants with other adverse events in each risk group. These entries are separate from the primary endpoint, and the registry does not say whether the serious events were considered treatment-related or whether they met the primary endpoint's degree criteria.

The listed serious-event terms are Increase in liver enzymes at 20.0% and Died of pneumonia at 5.6%. Their denominators and relationship to treatment are not explained in the record. Death counts are shown as null, not as a numerical zero. The term Died of pneumonia should therefore be understood as a listed serious-event term, not as evidence that the registry establishes a treatment-related death.

These figures describe recorded events in this study. They do not by themselves establish causality, compare rare-event risks precisely, or rule out events not captured by the endpoint or follow-up.

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

The posted primary endpoint results show zero participants with vaccine-related degree 3 or 4 adverse events in each reported arm. This is a descriptive finding about the endpoint as defined in the registry, over follow-up described as up to 6 months after the end of treatment. It is not a statement that no adverse event of any severity occurred. Separate serious-adverse-event entries list affected participants in both treatment groups, and those entries do not establish whether the events met the primary endpoint definition or were related to treatment.

The result does not establish that AFO-18 is safe or unsafe in general. The study is a Phase I trial with enrollment listed as 18, and the primary outcome arm counts are reported separately. The registry provides no confidence interval for the primary result and no estimable comparative binary effect. Without a quantified interval or a detailed analysis, the precision of the comparison cannot be established from the posted primary results.

The trial also set out to assess immune responses, viral load, CD4 T-cell counts, and the feasibility of conducting therapeutic immunisation research in a poorly resourced African setting. The registry names the secondary outcomes but does not post comparative analyses for them. The primary safety counts therefore cannot answer whether the vaccine induced a T-cell response or changed viral load or CD4 counts.

In general, a small early-phase study can describe observed outcomes under its study conditions, while remaining limited in its ability to characterize uncommon events or determine differences between groups precisely. That general point does not imply a particular unobserved event rate for this trial. The posted data should be read as limited observations, with the endpoints, attribution rules, and reported denominators kept in view.

The record does not report enough detail to assess the randomisation process, masking procedures, missing-data methods, or a prespecified analysis plan. Those omissions limit appraisal of how the trial was conducted and how robustly the reported findings can be interpreted. The results do not by themselves support conclusions beyond the outcomes actually recorded.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how an early-phase safety question differs from an efficacy question. Its primary endpoint is a count of participants with vaccine-related degree 3 or 4 adverse events, not a measure of HIV control or immune response. The distinction matters because readers can otherwise overinterpret a safety count as answering the broader biological questions that motivated the intervention.

The record also illustrates why denominator definitions matter. Enrollment, primary-outcome arm counts, and serious-adverse-event risk groups are reported separately. Even when counts appear in the same registry record, each belongs to a particular outcome and population definition. Preserving those definitions avoids misleading comparisons and prevents a safety endpoint from being conflated with a separate serious-event listing.

A further statistical lesson is that matching zero event counts do not demonstrate equivalence between groups. General statistical reasoning requires attention to uncertainty, and the registry does not report a confidence interval or an estimable binary comparison for the primary endpoint. The observed counts can be described, but they do not quantify how closely the groups' underlying event risks may be alike.

The study also highlights the value of transparent reporting of participant flow, analysis populations, missing outcomes, and analysis methods. The registry includes a brief description of the analyzed population, but does not fully reconcile all denominators or report a detailed statistical analysis plan. Such information is needed to understand precisely which participants contribute to each result.

Finally, the listed secondary aims and the lack of posted analyses demonstrate why outcome titles alone are not evidence of findings. Clear separation of planned questions, observed counts, comparative estimates, and their uncertainty is central to interpreting clinical trial records responsibly.

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 posted primary result is limited to vaccine-related adverse events of degree 3 or 4. It does not provide a full description of all adverse events, their timing, duration, recurrence, or severity distribution. The registry does not give a detailed grading system or the criteria used to assign treatment relationship. Those details are not reported in the registry record.

Several population counts appear for different purposes: enrollment is listed as 18; the primary outcome arms report 16 participants in the Vaccinee group and 4 in the Placebo group; and serious-adverse-event risk groups report 18 at risk for AFO-18 and 5 at risk for Saline. The record does not fully reconcile these denominators. The primary population description mentions exclusions for loss to follow-up or withdrawal and inclusion of two participants whose physicians stopped participation because of serious adverse events considered unrelated to vaccine or placebo, but does not provide complete participant flow.

The serious-adverse-event terms include percentages, but their denominators and attribution are not specified in the record. Death counts are not numerically reported. The listing of Died of pneumonia does not establish the treatment relationship or how it maps to the primary endpoint.

The registry does not report a confidence interval for the primary endpoint, a detailed statistical analysis plan, a sample-size justification, the randomisation procedure, or who was masked. It also does not report the handling of missing outcome data or a multiplicity strategy. Although secondary outcomes are listed, comparative analyses are not posted. These omissions limit assessment of precision, potential bias, and the strength of any between-group interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease — NCT01141205.
• Registry record last updated 2013-08-08; status last verified 2013-08.
• Results first posted 2012-10-15.
• 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

NCT01141205 is a completed randomized, single-masked, parallel-group Phase I study sponsored by Statens Serum Institut. It evaluated AFO-18 peptide immunisation with CAF01 versus saline in untreated, healthy individuals with chronic HIV-1 infection in West Africa. Enrollment is listed as 18; the registry records a study start of 2009-08 and primary completion of 2012-06.

The primary outcome was the number of participants with vaccine-related degree 3 or 4 adverse events up to 6 months after treatment ended. The posted count is zero in each primary outcome arm. Separate serious-adverse-event entries report 1 affected participant in each risk group, with different reported denominators, and list serious-event terms including Increase in liver enzymes and Died of pneumonia.

The registry lists secondary immune and clinical outcomes but no analyses. It does not report a confidence interval for the primary endpoint, a detailed analysis plan, or a complete reconciliation of the reported populations. The results therefore support a descriptive reading of the recorded safety counts, with substantial limits on comparative precision and interpretation.