Combinatorial Therapy to Induce an HIV Remission: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combinatorial Therapy to Induce an HIV Remission (NCT04357821), a na phase 1, phase 2 study. The primary outcome is Grade 3 or Greater Adverse Event Count.

2. Clinical Question

3. Trial Design

This is a completed phase 1/phase 2 study with a single-group design. The registry lists the allocation as not applicable and masking as none. All volunteers were assigned to the combination intervention arm; no separate comparator arm is described. Consequently, the study is not a randomized comparison and cannot estimate an intervention-versus-control contrast from the record.

The intervention is described as a combination regimen involving a therapeutic conserved element DNA vaccine, an MVA vaccine boost, a TLR9 agonist, and broadly neutralizing antibodies. The brief summary says participants receive the regimen during ART and then undergo an analytic treatment interruption. The registry does not provide further detail about the interruption procedures or the criteria used to assess remission.

The listed enrollment is 11. There is a difference between that enrollment figure and the brief summary, which describes 20 individuals as the planned study population. The record does not explain this difference, so the planned figure should not be treated as the number enrolled or as an observed analysis population. The primary endpoint description identifies all 11 enrolled participants as its population.

The study is marked completed. Its recorded start date is 2020-08-01, and its primary completion date is 2024-01-29. These record details describe study status and timing; they do not provide results for the primary endpoint. The registry lists secondary outcomes covering adverse events, T cell responses, and intact provirus DNA levels. It reports no analyses for those outcomes in the record.

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: The study enrolled 11 individuals. The study was terminated early for one participant as one of the investigational products was set to expire before planned dosing. Ten individuals received the complete set of interventions.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All 11 participants who were enrolled

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 Grade 3 or Greater Adverse Event Count, measured over Week 0 through 102.

The primary endpoint is the count of participants who experience a new grade 3 or greater adverse event during Week 0 through 102. The unit is participants, and the endpoint description specifies all 11 enrolled participants as the population. This is a participant-based safety outcome: it concerns whether participants experience an event meeting the stated severity threshold, rather than the total number of event episodes.

Safety endpoints are used to describe the occurrence and severity of adverse events during a study. A threshold such as grade 3 or greater focuses attention on events meeting a specified severity level. The endpoint’s stated timeframe defines the period over which events are considered. These features make the outcome interpretable as a safety measure for the enrolled group, but they do not by themselves establish whether an event was caused by the intervention.

The registry record identifies the endpoint but does not report its observed count. The serious adverse event figures listed elsewhere in the record are not interchangeable with this endpoint: serious status and grade 3 or greater severity are distinct classifications, and the record does not state that the counts refer to the same set of events or participants. Therefore, the serious-event figures should not be used as a substitute for the missing primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is single group: participants receive the combination intervention, and the record does not describe a concurrent control arm. Allocation is listed as not applicable, and masking as none. This design can document outcomes observed during the study, but it does not provide the randomized between-group contrast that would help distinguish intervention effects from changes that might occur for other reasons. General statistical interpretation of an uncontrolled study should therefore emphasize description rather than causal attribution.

What does a participant count represent?

The primary outcome is a count of participants who experience a new grade 3 or greater adverse event. A participant count is different from an event count. A participant may experience more than one event, but the endpoint as written counts participants meeting the event definition rather than counting every occurrence. The record gives the unit and the outcome description, but it does not report the observed primary count. It is therefore not possible to use the available serious-event summary to fill in that result.

The serious adverse event summary reports affected participants, while its term list supplies percentages for selected serious-event terms. These summaries answer different descriptive questions from the primary endpoint. In general, adverse-event severity and seriousness are separate ways of classifying events. An event’s grade does not automatically determine whether it meets a serious-event definition, and the registry record does not provide a mapping between the two classifications in this study.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. Its width depends in part on the amount and variability of information available. A narrow interval indicates greater statistical precision under that method; a wide interval indicates less precision. The registry record does not report confidence intervals for the primary endpoint or the adverse-event counts. The posted participant counts should therefore be read as descriptive observations, not as precise estimates of an underlying event risk.

Why does the design affect interpretation?

In a randomized comparison, allocation is used to make groups more comparable in expectation, allowing a between-group contrast to inform the estimated effect of an intervention. That logic does not apply to this single-group record because it has no separate control arm. An event observed after exposure cannot, from timing alone, be attributed to the intervention. Participant characteristics, the underlying condition, other care, and chance may also contribute. These are general considerations; the record does not provide analyses that quantify their roles.

The intervention combines several components. A descriptive outcome for the combination cannot identify which component, if any, contributed to an event or outcome. This is a general limitation of evaluating a regimen as a package rather than comparing its components in a design that can separate their effects. No component-specific comparison is reported in the registry record.

How should the planning assumptions be read?

The registry includes a statement describing planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, and distinguishes participant-per-arm illustrations from total-event illustrations for time-to-event outcomes. These are planning assumptions, not evidence that the trial used that design. In particular, an equal-allocation illustration does not change the fact that the registered study is single group. Sample-size illustrations are not observed power and should not be interpreted as a trial result.

The record does not report the trial’s own sample-size justification, a statistical analysis plan, interim analyses, or a calculated analysis for the primary outcome. It also reports zero analyses in the registry record. Without the analysis methods and corresponding results, it is not possible to assess whether a reported estimate was adjusted, which test was used, or how uncertainty was handled. General statistical concepts can clarify what analyses would mean, but they cannot replace missing trial-specific methods or results.

Why can over-dispersion matter?

In general, count data may vary more than a simple statistical model assumes. This is called over-dispersion, and ignoring it can make uncertainty appear smaller than it is. It is relevant when analyzing event counts, particularly when participants can have multiple events or when event rates differ substantially across participants. The primary endpoint is a count of participants with an event, not a reported total event count, and no dispersion estimate or model is reported. No over-dispersion adjustment can therefore be attributed to this record.

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("Combination Intervention Arm")
n      <- c(11)
events <- c(2)
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  Combination Intervention Arm  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: grade 2, 3 or 4 adverse events through Week 62; serious adverse events, medically attended adverse events, and potentially immune-mediated medical conditions; T cell response magnitude and breadth; and intact provirus DNA levels. It also lists 11 outcome measures. The record reports zero analyses. These listings identify outcomes of interest, but do not show which were analyzed or what results were obtained.

When a study evaluates multiple outcomes or performs multiple statistical tests, the chance of finding an apparently noteworthy result by chance can increase. General methods for addressing multiplicity include prespecifying a primary outcome, defining a testing sequence, or adjusting inference across tests. The registry record does not report a multiplicity strategy, a statistical analysis plan, or an analysis hierarchy beyond identifying the primary endpoint. No particular method should be assumed.

The primary endpoint population is described as all 11 enrolled participants. The record does not explain how missing outcome information, withdrawals, or incomplete follow-up were handled. It does not report the completeness of data through Week 102, nor does it describe an imputation method or sensitivity analysis. Absence of a reported missing-data method does not establish that no data were missing.

The analysis populations for the secondary outcomes are not reported in the registry record. The stated population for the primary endpoint should not automatically be extended to other outcomes. Without outcome-specific denominators and analysis details, the listed safety counts and outcome names cannot establish the completeness or comparability of each analysis.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: elevated alt (9.1%), hypomania (9.1%), suicide attempt (9.1%).

The serious adverse event summary for the combination intervention arm reports 3 participants with a serious adverse event and 11 participants with another adverse event. The record reports 0 deaths. The top serious-event terms are elevated ALT, hypomania, and suicide attempt, each listed with 9.1%. These are descriptive entries in the registry record; they do not by themselves establish that the intervention caused an event.

Seriousness and severity grade are distinct classifications. The primary endpoint concerns new grade 3 or greater adverse events, while the figures above concern serious adverse events and other adverse events. The registry record does not provide enough information to treat these summaries as the primary endpoint result or to infer how the classifications overlap. The primary endpoint’s observed count is not reported in the registry record.

The record does not give further detail on event timing, recurrence, duration, attribution, or the number of event episodes associated with each participant. The term-level percentages should not be combined or treated as a complete account of all events. With no comparator arm, the counts describe what was recorded in the intervention group and do not estimate an excess relative to another group.

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

The record establishes that a completed single-group phase 1/phase 2 study evaluated a combination intervention in participants with HIV/AIDS. It specifies an enrollment of 11 and identifies a safety endpoint concerning new grade 3 or greater adverse events over Week 0 through 102. It also reports serious adverse event and other adverse event participant counts, selected serious-event terms, and no deaths.

Those details do not establish whether the combination induced HIV remission. Although remission is part of the study’s stated aim, the registry record does not report an analysis showing whether remission occurred or how long any control lasted. It also does not report analyses of the listed T cell response or intact provirus DNA outcomes. A stated aim and a completed study status are not substitutes for outcome results.

The record also does not establish that the intervention caused or prevented the reported adverse events. Without a control group, the event counts are descriptive of the participants in the intervention arm. The serious adverse event figures cannot stand in for the primary endpoint because the record does not equate serious status with grade 3 or greater severity, and it does not report the primary endpoint count itself.

These limitations do not mean that no outcomes were measured or that no events occurred. Rather, the registry record does not include the analyses needed to answer those questions fully. Interpretation should distinguish observed descriptive counts from unreported endpoints, and should not turn missing statistical results into a conclusion of benefit, harm, or absence of effect.

14. Why This Trial Matters Statistically

This study illustrates why trial design and outcome reporting need to be read together. The registry describes a single-group intervention study, so its event summaries can characterize what happened in the enrolled group but cannot provide a randomized comparison with a control group. That distinction remains important even when an outcome is clearly defined and a study is marked completed.

It also illustrates the importance of keeping safety outcomes distinct. A primary endpoint based on participants with new grade 3 or greater adverse events is not interchangeable with a summary of serious adverse events. When the primary endpoint result is not reported, related but differently defined safety counts should not be used as a proxy. Doing so could misstate what the registered endpoint measured.

The registry’s stated interest in HIV remission and immune-related outcomes makes the difference between study rationale and reported evidence especially consequential. The record identifies those scientific aims and lists relevant secondary outcomes, but provides no analyses for them. A careful statistical reading keeps the interpretation tied to results actually reported, rather than assuming that a study’s objectives were achieved.

Finally, the difference between the listed enrollment and the planned population described in the brief summary highlights why planned and enrolled populations should be distinguished. The record does not explain that difference. Treating the planned number as the observed sample could misrepresent the evidence available for interpreting the study. These are general lessons in transparent registry interpretation, grounded in the design and reporting details of this record.

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 most important limitation for interpreting the primary safety outcome is that the record defines the endpoint but does not report its observed count. The serious adverse event summary is not a substitute: the primary outcome concerns grade 3 or greater events, while seriousness is a separate classification, and their relationship is not reported.

The study has a single-group design, with no separate comparator described. As a result, the record provides no like-for-like control comparison for safety outcomes or for the study’s remission aim. The combination intervention includes several components, and the record does not describe component-specific comparisons that could separate their contributions.

The registry reports enrollment of 11, whereas the brief summary describes 20 individuals as the planned population. It does not explain the difference. The primary endpoint population is stated as all 11 enrolled participants, but outcome-specific analysis populations and follow-up completeness are not reported.

The record lists secondary outcomes but reports no analyses. It does not report the trial’s statistical analysis plan, multiplicity handling, interim analyses, missing-data methods, confidence intervals, or adjusted estimates. The timing, recurrence, and attribution of individual adverse events are also not described in the available record. These omissions limit assessment of precision, completeness, and causal interpretation; they should not be treated as evidence that analyses or events were absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combinatorial Therapy to Induce an HIV Remission — NCT04357821.
• Registry record last updated 2026-08-28; status last verified 2026-08.
• Results first posted 2026-02-24.
• 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

NCT04357821 is a completed phase 1/phase 2, single-group study of a combination intervention for HIV/AIDS. The registry lists enrollment of 11, allocation as not applicable, and masking as none. The intervention includes a therapeutic conserved element DNA vaccine, an MVA vaccine boost, a TLR9 agonist, and broadly neutralizing antibodies. The brief summary describes treatment during ART followed by ATI.

The primary endpoint is the number of participants with a new grade 3 or greater adverse event from Week 0 through 102, among all 11 enrolled participants. Its observed count is not reported in the registry record. The safety summary reports 3 participants with a serious adverse event, 11 with another adverse event, and 0 deaths. The record lists 11 outcome measures and zero analyses.