iHIVARNA Clinical Trial in HIV Infected Individuals: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for iHIVARNA Clinical Trial in HIV Infected Individuals (NCT02888756), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0.

2. Clinical Question

The registry describes a randomized, double-blind, parallel-group study. Its stated focus was safety and immunogenicity of iHIVARNA-01 in people with chronic HIV infection who were receiving stable antiretroviral therapy. The primary endpoint is a count of participants with qualifying treatment-related adverse events, rather than a measure of viral load or immune response. The registered secondary outcomes include immunogenicity, time to viral rebound, change in plasma viral load, functional cure, vaccine-related immune responses, viral suppression mediated by CD8 T cells, proviral DNA reservoir, and viral immune escape.

The posted primary endpoint count is zero in each arm: iHIVARNA-01, TriMix, and placebo. Those counts describe the recorded endpoint at week 6. They do not answer every safety or immunogenicity question raised by the trial, and the registry does not report a comparative estimate for this endpoint. Further details about eligibility, the intended estimand, or the study’s formal hypotheses are not reported in the registry record.

3. Trial Design

This was a phase IIa randomized, placebo-controlled, double-blind study with a parallel-group model. The registry lists three arms: iHIVARNA-01, TriMix, and placebo. It records enrollment of 33 participants. The trial status is terminated. The recorded start date is 2017-04-04 and the primary completion date is 2018-02-12.

The iHIVARNA-01 arm is described as receiving 1200μg mRNA, consisting of 900 μg HIV mRNA and 300 μg TriMix mRNA, in three vaccinations spaced two weeks apart. The TriMix arm is described as receiving 300 μg TriMix mRNA on the same vaccination schedule. The placebo arm received water for injection on that schedule. The study summary describes iHIVARNA-01 as a therapeutic vaccine and identifies intranodal administration. Additional procedural details are not reported in the registry record.

The official title describes participants as chronically HIV-infected patients under stable combined antiretroviral therapy. The registry’s brief summary states that the intervention was intended to stimulate immune activity and describes a goal of controlling viral replication without antiretroviral therapy. That statement describes the rationale and aim, not a result established by the posted primary endpoint. The primary outcome assessed treatment-related adverse events through week 6. It was defined using specified local, systemic, and other clinical or laboratory events of grade 3 or above, as well as vaccination-attributable events leading to discontinuation of the immunisation regimen.

The registry lists multiple secondary outcomes, including immune response and virological measures. It does not report detailed eligibility criteria, recruitment procedures, adherence, follow-up completeness, or reasons for termination. Nor does it report the planned allocation ratio, the method used to generate the random sequence, or how masking was maintained. Those design details are not reported in the registry 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.

Vaccination Period

Analytical Treatment Interruption

Reasons for not completing this period:

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 Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0, measured over week 6.

The primary endpoint is the number of participants with treatment-related adverse events assessed using CTCAE v4.0 at week 6. The registry definition includes grade 3 or above local events, such as pain or cutaneous reactions; grade 3 or above systemic events, including temperature, chills, headache, nausea, vomiting, malaise, and myalgia; and grade 3 or above other clinical or laboratory events confirmed at examination or repeat testing. It also includes any event attributed to vaccination that led to discontinuation of the immunisation regimen.

This endpoint is a count of participants meeting the definition, not a count of all event episodes. A participant with more than one qualifying event would still be represented as a participant in this measure; the registry description does not give an event-level analysis. The posted count is zero in each of the three arms. These counts concern the defined treatment-related endpoint at week 6; they should not be conflated with the separate serious adverse event summaries, which are reported elsewhere in the registry record.

In general, a prespecified safety endpoint provides a consistent way to describe events considered important to monitor during a trial. Restricting the endpoint to events meeting stated severity or discontinuation criteria can make the measure clinically focused, while also meaning it does not represent every symptom or all-cause event. The registry does not report further details about endpoint adjudication, attribution procedures, or the analysis population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a randomized parallel-group trial assigns participants to separate intervention groups and compares outcomes across those groups. Random allocation is intended to reduce systematic differences between groups, while masking is intended to limit the influence of treatment knowledge on participant experience, care, and outcome assessment. This record describes the study as randomized and double-blind. It does not report the allocation-generation method, the people masked, or procedures for preserving masking, so those operational details are not reported in the registry record.

What kind of outcome is the primary endpoint?

The primary endpoint is binary at the participant level: each participant either meets the stated treatment-related adverse event definition during the specified timeframe or does not. The registry reports the number meeting the definition in each arm. A count is not an event rate unless it is expressed relative to an appropriate denominator, and the endpoint is specifically a count of participants rather than a count of event episodes. The posted counts are zero for iHIVARNA-01, zero for TriMix, and zero for placebo; the arm sizes are 16, 9, and 8.

In general, comparisons of binary outcomes may be expressed as differences in proportions, ratios, or odds-based measures. Each summary answers a somewhat different question and requires a defined analysis approach. The registry record does not report an effect estimate or confidence interval for a two-arm comparison of this endpoint. Its analysis note says values are missing or not estimable for a two-arm comparison. With zero recorded events in every arm, the registry does not provide an estimated treatment contrast to interpret.

What does a confidence interval add?

In general, a confidence interval communicates the precision of an estimated effect, in addition to its direction and magnitude. Wider intervals indicate less precision, while narrower intervals indicate greater precision under the assumptions of the method used. An interval can include effects in more than one direction, illustrating that an observed point estimate alone may not resolve uncertainty. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be assessed from an interval-based comparison.

Small group sizes and sparse binary outcomes can make comparative estimates imprecise or difficult to estimate. In general, methods for sparse data may behave differently from large-sample approximations, especially when one or more groups have no observed events. The registry’s analysis note explicitly marks the two-arm binary comparison as missing or not estimable. It does not state which statistical procedure was attempted, whether any alternative method was used, or whether an adjustment was considered. Those details are not reported in the registry record.

How should the endpoint definition be read?

The endpoint combines specified adverse events meeting a severity threshold with vaccination-attributable events leading to discontinuation. This makes it a defined safety summary rather than a complete inventory of all symptoms, diagnoses, or laboratory changes. In general, combining qualifying events can provide a compact summary but may conceal differences in the kinds of events that contribute to the outcome. Here, the primary counts are all zero, and the registry does not provide event-level detail for that endpoint.

The primary endpoint has a stated timeframe of week 6. In general, an endpoint measured over a particular timeframe describes events captured under that timeframe and should not automatically be interpreted as covering a longer period. The registry also provides separate adverse event summaries, but it does not report how their observation periods relate to the week 6 primary endpoint or whether individual events overlap between summaries.

What do planning illustrations mean?

In general, a sample-size calculation uses assumptions about the effect to detect, the significance level, allocation, and statistical method. A planning illustration is not an observed outcome and is not a measure of the study’s achieved power. The registry record states that its planning illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is the total number of events; for other outcomes, it is participants per arm. The specific planning results are not reported in the registry record, and these assumptions are not evidence that the trial used them for its original design.

The registry lists one analysis and does not report the analysis method, covariate adjustment, handling of multiplicity, or the prespecified analysis population. The discrepancy indicator is false, and no recalculated comparison is available for this binary endpoint. In general, a recalculation from summary statistics is an unadjusted calculation and does not replace a sponsor’s own analysis when the two differ. No sponsor comparison is presented for this endpoint in the registry 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("iHIVARNA-01", "TriMix", "Placebo")
n      <- c(16, 9, 8)
events <- c(0, 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  iHIVARNA-01  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5
ARM  TriMix  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Placebo  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 secondary outcomes posted, spanning immune response, viral rebound, plasma viral load, functional cure, CD8 T cell mediated viral suppression, proviral DNA reservoir, and viral immune escape. It also records 12 outcome measures and one analysis. The relationship among these entries and the analysis record is not explained in the registry record. The primary endpoint is the count of participants with treatment-related adverse events at week 6.

When a study evaluates multiple outcomes or performs multiple comparisons, the chance of a false positive finding can increase if each is interpreted without considering multiplicity. In general, prespecified outcome hierarchies or statistical adjustments can help manage that issue. The registry record does not report whether multiplicity was addressed, which outcomes were included in the recorded analysis, or whether any outcomes were designated as exploratory. The registry entries therefore do not establish how secondary findings should be ranked or interpreted inferentially.

The primary endpoint counts are reported for each arm, but the record does not describe missing outcome data, participant exclusions, or the denominators used in a formal analysis population. It also does not report whether all randomized participants were analyzed according to assigned arm, how withdrawals were handled, or whether any imputation was used. Those details are not reported in the registry record. Without this information, completeness and analysis-population choices cannot be evaluated from the registry entries.

The registry status is terminated. The reason for termination, any changes to the analysis plan, and the timing of those changes are not reported in the registry record. No sample-size justification or interim-analysis plan is reported. These omissions limit assessment of whether the outcome reporting and analysis followed a prespecified plan.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (12.5%), colitis (6.2%), pancreatitis (6.2%).

The serious adverse event summary reports 2 affected participants in the iHIVARNA-01 arm, 0 in the TriMix arm, and 1 in the placebo arm. It records no deaths in any arm. The registry also lists depression at 12.5%, colitis at 6.2%, and pancreatitis at 6.2% among the top serious adverse event terms. The available record does not assign each term to a particular arm, so those percentages should not be read as arm-specific figures.

These serious adverse event summaries are distinct from the primary endpoint. The primary endpoint counts participants with treatment-related events meeting its specified criteria at week 6. The serious-event figures do not, in the registry entries, establish treatment attribution or show whether serious events met the primary endpoint definition. The registry does not report event narratives, timing, duration, outcome, or whether one participant experienced multiple serious events.

In general, serious adverse events are an important safety category, but counts alone do not establish causation. Differences in counts across arms can be difficult to interpret in a small trial, particularly without event details and a comparative estimate with uncertainty. The reported counts should therefore be read descriptively, alongside the distinct primary safety definition, rather than as evidence that an event was caused by an intervention.

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

The primary safety result is straightforward as a descriptive record: no participants in any of the three arms were recorded as meeting the treatment-related adverse event definition at week 6. The arm sizes are 16 for iHIVARNA-01, 9 for TriMix, and 8 for placebo. Because the registry does not report a comparative estimate or confidence interval, the primary endpoint does not quantify how much the arms may differ or how precise such a difference would be.

This result does not establish that no adverse events occurred. It concerns a specific endpoint definition that includes grade 3 or above events in specified categories and vaccination-attributable events leading to discontinuation. Other adverse events are reported separately in the registry. The record also includes serious adverse event counts and serious-event terms, which are not interchangeable with the primary endpoint and are not fully linked to treatment attribution in the registry entries.

The result also does not establish that the interventions are equivalent, that rare events cannot occur, or that longer-term safety is known. In general, absence of observed events in a study does not demonstrate absence of underlying risk, and a small study may provide limited precision. No interval estimate is reported for this primary endpoint. The registry’s status is terminated, but the reason for termination is not reported.

The study’s brief summary describes a goal related to control of viral replication without antiretroviral therapy. That aim is not measured by the primary safety endpoint. Although the registry lists secondary immune and virological outcomes, their results are not described in the registry entries. The primary endpoint therefore cannot establish immunogenicity, viral rebound timing, change in plasma viral load, functional cure, or changes in the proviral DNA reservoir.

In general, interpretation should separate the trial’s rationale from its recorded outcomes. The rationale describes why an intervention was studied; outcome data indicate what was recorded for a defined measure, population, and timeframe. The posted primary result is limited to the week 6 safety count. It is not a basis for medical advice or a conclusion about the overall benefit or risk of treatment.

14. Why This Trial Matters Statistically

This trial illustrates the difference between a descriptive safety count and a comparative treatment estimate. The registry reports zero participants meeting the primary treatment-related adverse event definition in each arm, but it does not report an estimable two-arm comparison. A reader can identify the recorded counts, yet cannot infer a precise between-arm difference or its uncertainty from the posted primary endpoint alone.

It also highlights why endpoint definitions matter. The primary outcome uses a particular severity threshold and includes a discontinuation criterion, while serious adverse events are summarized separately. These measures answer related but distinct safety questions. Treating them as interchangeable would blur differences in attribution, severity, and event definition that the registry does not resolve.

The record also demonstrates the importance of distinguishing study aims from results. The brief summary describes a therapeutic-vaccine rationale and a goal related to viral control without antiretroviral therapy. The primary endpoint, however, is a week 6 safety count. The registry lists immune and virological secondary outcomes, but their results are not reported in the registry entries. Statistical interpretation must remain tied to the outcome actually reported.

Finally, a terminated trial with limited posted comparative detail raises questions about completeness and analysis choices. The registry record does not report the reason for termination, missing-data handling, analysis populations, multiplicity procedures, or the statistical method used for the primary comparison. Those omissions matter because they constrain assessment of precision, robustness, and the relationship between planned and reported analyses. The appropriate statistical conclusion is therefore deliberately narrow: the posted primary counts are zero in all arms, while a comparative estimate and its uncertainty are not reported.

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 primary endpoint is reported as counts without a comparative effect estimate or confidence interval. The analysis note states that values are missing or not estimable for a two-arm comparison of the binary endpoint. This prevents assessment of the magnitude and precision of a treatment contrast from the posted primary result. The counts are also based on modest arm sizes, and zero recorded events should not be interpreted as proof that the underlying risk is absent.

The endpoint is limited to events meeting its specified definition and timeframe. The registry does not report further information about event adjudication, attribution procedures, exposure duration, or the relationship between primary-endpoint events and the separate serious adverse event summaries. Serious-event terms are listed with percentages, but the registry entries do not identify the arm associated with each term. Event timing, outcomes, and participant-level overlap are not reported.

Important design and analysis details are unavailable. The registry record does not report the reason for termination, recruitment or follow-up completeness, missing-data handling, the analysis population, the statistical procedure for the primary endpoint, or whether multiplicity was addressed. It also does not report a sample-size justification, an interim-analysis plan, or the original statistical analysis plan. These gaps limit evaluation of whether the observed summaries represent all randomized participants and whether analyses followed prespecified procedures.

The registry lists secondary immune and virological outcomes, but their results are not included in the registry entries. Consequently, the primary safety result cannot be used to evaluate those outcomes or the stated functional-cure goal. Generalizability is also difficult to assess because detailed eligibility criteria and participant characteristics beyond the official title are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: iHIVARNA Clinical Trial in HIV Infected Individuals — NCT02888756.
• Registry record last updated 2019-12-23; status last verified 2019-12.
• Results first posted 2019-12-09.
• 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

The registry describes a phase IIa randomized, double-blind, placebo-controlled parallel-group study of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy. It records enrollment of 33 participants, a start date of 2017-04-04, a primary completion date of 2018-02-12, and terminated status.

The three arms were iHIVARNA-01, TriMix, and placebo. The primary endpoint was the number of participants with treatment-related adverse events assessed using CTCAE v4.0 at week 6. The posted counts were zero in each arm. A comparative estimate for this binary endpoint is not reported; the analysis note indicates that a two-arm comparison was missing or not estimable.

The separate serious adverse event summary records 2 affected participants in the iHIVARNA-01 arm, 0 in the TriMix arm, and 1 in the placebo arm, with no deaths recorded in any arm. Secondary outcomes include immune and virological measures, but their results are not reported in the available the registry entries. The reason for termination and key details of missing-data and analysis procedures are not reported in the registry record.