A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients (NCT01199939), a na phase 2 study. The primary outcome is Number of Participants With Confirmed Virologic Response (CVR) at Week 48.

2. Clinical Question

3. Trial Design

This was a completed Phase II, multicenter, single-arm, open-label study. The registry record lists enrollment as 54. Its brief summary describes a study of 50 adult patients, while the arm description gives the regimen and treatment period. These are different statements in the record: enrollment is listed as 54, and the brief summary describes 50 patients. The record does not explain the difference.

All participants were assigned to the same treatment group, labelled ETR + DRV/rtv. The regimen was oral etravirine 400mg, darunavir 800mg, and ritonavir 100mg, each once daily for 48 weeks. With no separate control arm and no masking, this study was designed to observe outcomes during treatment rather than to estimate a randomized treatment contrast. The allocation field is NA and the model is single group.

The registry lists the study start as 2010-05 and primary completion as 2012-10, and gives the status as completed. The primary endpoint was assessed at Week 48. The brief summary describes a 6-week screening period and says the end-of-study endpoint was met either by completing the Week 48 visit or by early termination for any reason.

In addition to the primary virologic outcome, the listed secondary outcomes include changes from baseline in log10 plasma HIV-1 viral load at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 30, and Week 36. The summary also mentions safety measurements and assessments of metabolic, inflammatory, immune restoration, and bone markers. The registry record does not report detailed procedures for these assessments or a statistical analysis plan.

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: 54 participants were treated with Etravirine and Darunavir/ritonavir in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-To-Treat Non-Virologic failure (VF) censored: Participants who took at least one dose of any of the study medications and did not withdraw for reasons other than VF or experienced VF prior to discontinuation. Participants with evaluable data at Week 48

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 Confirmed Virologic Response (CVR) at Week 48, measured over Week 48.

The primary endpoint is the number of participants with confirmed virologic response at Week 48. The registry defines response as confirmed plasma HIV-1 RNA below 50 copies/mL. This is a binary outcome at the participant level: a participant either meets the stated response definition or does not. The endpoint is reported as a count, not as a continuous change in viral load.

As a general statistical explanation, a threshold-based virologic endpoint provides a clinically interpretable way to describe whether a participant’s measured viral load falls below a prespecified level and is confirmed. The word “confirmed” matters because the definition requires confirmation, rather than relying on a single measurement. The registry record does not give further details about how confirmation was established, the timing or number of measurements, or how results near the threshold were handled.

The population definition also affects what the endpoint count would mean. The record describes an intent-to-treat population with non-virologic failure censoring, participants who took at least one dose, and evaluable Week 48 data. It does not report the number of participants in this analysis population or the number meeting the response definition. Therefore, the endpoint can be described precisely, but its observed result and the precision of any estimate cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant count. In general, a binary endpoint classifies each participant according to whether a defined event or response occurred. A count is meaningful alongside its denominator: the same count can correspond to different rates when the numbers of participants assessed differ. The registry record names the response definition and analysis population, but it does not report the observed count or the denominator for the Week 48 analysis. No response rate can therefore be described from the record.

As a general statistical explanation, an estimate of an event frequency is often accompanied by a confidence interval. A confidence interval communicates uncertainty about the population value compatible with the data and the method used. Its width depends in part on the amount of information in the analysis. Because the response count and denominator are not reported, neither a response estimate nor its interval can be interpreted for this endpoint. A confidence interval would describe statistical uncertainty, not remove limitations caused by the design or establish a causal treatment effect.

The design is single-group, not randomized. General statistical interpretation of a single-group study is primarily descriptive: outcomes can be reported among the participants observed, but the study does not contain a concurrent randomized contrast. Differences over time or comparisons with values from elsewhere can be affected by differences in populations, measurement, follow-up, and other factors. The registry record does not report an external comparison or a method for adjusting one.

The primary population description includes non-virologic failure censoring and requires evaluable data at Week 48. In general, censoring means that some observations do not contribute follow-up beyond a defined point or event under the analysis rules. The meaning of a censored observation depends on the outcome and the analysis method. The registry record gives a population description, but does not report how many participants were censored, how missing Week 48 data were handled, or the detailed analysis method. The extent to which these rules affected the endpoint is therefore not reported in the registry record.

Multiplicity concerns arise when a study assesses multiple outcomes or makes multiple statistical tests. In general, the more questions examined, the greater the chance that at least one result may appear noteworthy by chance if testing is not accounted for. The record lists a primary endpoint and multiple secondary outcomes, including viral-load changes at several visits. It does not report a multiplicity adjustment, a testing hierarchy, or a complete statistical analysis plan. It would be inappropriate to assume that any particular adjustment or sequence of tests was used.

The record’s sample-size assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used a two-arm design. The actual trial is single-group. The registry record does not report the trial’s own sample-size justification or the numerical output of a planning calculation. Any sample-size illustration is a planning aid, not observed power, and cannot replace the missing outcome result.

As a general explanation, over-dispersion is relevant when the variability in count data exceeds what a chosen statistical model expects. Accounting for it can affect uncertainty estimates. The primary endpoint is described as a participant count, and the record does not identify an over-dispersion model or provide a dispersion estimate. No conclusion about over-dispersion or a model-based adjustment can be drawn from the registry record.

The registry records zero analysis entries. That does not reveal which statistical procedures were used in any analyses outside the registry record. The endpoint definition, outcome list, and population description do not establish the estimation method, hypothesis tests, covariate adjustments, handling of protocol deviations, or missing-data assumptions. Those details are not reported 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("ETR + DRV/Rtv")
n      <- c(45)
events <- c(40)
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  ETR + DRV/Rtv  45  40  88.9  75.9  96.3  76.5  95.2  76.4  95.1

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary endpoint and several secondary outcomes, including viral-load changes from baseline at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 30, and Week 36. Multiple outcome assessments can create multiplicity: when many hypotheses are examined, the chance of at least one apparently unusual result can increase. As a general statistical principle, prespecifying a testing hierarchy or adjusting for multiple comparisons can help control that issue. The registry record does not report whether either approach was used, or provide a detailed statistical analysis plan.

The Week 48 endpoint population is defined using treatment exposure, non-virologic failure censoring, and evaluable data. However, the record does not report the number of participants with evaluable Week 48 results, the number excluded from the analysis, the extent of missing outcome data, or the specific missing-data methods. The brief summary allows for early study termination, but it does not say how such cases were handled in the primary analysis. The effect of missing data on the result cannot be assessed.

The record describes an intent-to-treat non-virologic failure censored population, but does not provide a full account of analysis populations or how participants with different follow-up or discontinuation circumstances were classified. The primary result and its denominator are not reported in the registry record. Details about interim analyses, protocol deviations, and sensitivity analyses are also not reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fatigue (1.9%), pyrexia (1.9%), abscess jaw (1.9%), pneumonia (1.9%), hodgkin's disease (1.9%).

The registry record reports 3 participants with serious adverse events among 54 at risk in the ETR + DRV/Rtv group. It separately reports 28 participants with other adverse events among 54 at risk. These are participant counts, and they should be read as recorded events in the single study group, not as a comparison between treatments. The serious-event terms listed are Fatigue, Pyrexia, Abscess Jaw, Pneumonia, Hodgkin's Disease, and Dyspnoea; each is reported with a frequency of 1.9%.

The listed terms do not, by themselves, establish how many participants experienced each type, whether participants experienced more than one term, or how events related to treatment. The registry record does not report those details. The deaths field has no reported count in the available record, so deaths are not reported in the registry record.

As a general statistical point, adverse-event counts are interpreted in the context of how events were defined, collected, and followed. A single-group study cannot estimate a comparative excess or reduction in risk against a control group. The posted safety figures describe what was recorded for this group; they do not establish a causal relationship or support a treatment comparison.

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

The registry record establishes that a completed Phase II, open-label, single-group study evaluated once-daily etravirine with darunavir/ritonavir in adults with HIV described as early treatment-experienced. It specifies the regimen, the planned treatment period, the primary Week 48 endpoint, and the definition of confirmed virologic response. It also records serious and other adverse-event participant counts for the study group.

However, the record does not report the primary response count, the Week 48 analysis denominator, a response estimate, or its statistical uncertainty. The stated endpoint and design cannot substitute for those results. The registry record therefore does not allow readers to quantify the observed virologic response or how precisely it was estimated.

The single-arm, open-label design also limits what can be concluded from any observed outcome. There is no concurrent randomized comparator to distinguish outcomes under the regimen from changes that might have occurred for other reasons. The design cannot establish a comparative treatment effect. This limitation remains even if an outcome estimate is available from another source; such a comparison is not reported in the registry record.

The safety counts describe participants with recorded events, not comparative safety. The listed serious-event terms and their frequencies do not determine causality, severity beyond their registry classification, or whether events occurred in the same participants. Detailed event-level results and a death count are not reported in the registry record.

In general, trial results are best interpreted by considering the endpoint definition, analysis population, missing data, uncertainty, and study design together. Here, key efficacy analysis details and the primary result are absent from the registry record. The record supports a description of the study and its planned question, but not a conclusion about the size or precision of the observed response or a comparison with another regimen.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the distinction between a defined endpoint and a reported result. The registry record gives a clear threshold-based definition for confirmed virologic response at Week 48, and it describes a population for that analysis. But it does not report the response count or denominator. Without those values, readers cannot calculate or interpret an observed response frequency, and cannot assess its precision.

It also illustrates why design determines the kinds of questions a study can answer. A single-group study can describe what happened among participants receiving one regimen. It cannot provide a randomized comparison with another regimen. The open-label design and lack of a control group should therefore remain central to interpretation, alongside the fact that the primary outcome is not reported in the registry record.

The study’s listed secondary viral-load outcomes occur at several follow-up visits, while the primary assessment is at Week 48. Such multiple outcomes and time points raise general questions about prespecification and multiplicity. Those questions cannot be resolved from the available record because a detailed analysis plan and multiplicity approach are not reported.

Finally, the record helps distinguish enrollment from an endpoint analysis population. Enrollment is listed as 54, whereas the primary population requires Week 48 evaluable data and applies specified censoring rules. The analysis denominator is not reported. That distinction matters because the endpoint’s interpretation depends on who contributed data to the analysis, not merely on the enrollment figure.

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 efficacy limitation is that the registry record does not report the Week 48 response count, its analysis denominator, an estimate, or a confidence interval. The outcome is defined, but the observed value and its precision cannot be evaluated from the record.

The study has no concurrent comparator and is open-label. Outcomes in the treated group cannot be interpreted as a randomized treatment contrast, and the design does not separate treatment-associated changes from other influences over time. The registry record does not report an external control or a comparative analysis.

The record lists enrollment as 54, while its brief summary describes 50 patients. It does not explain this difference. The number of participants meeting the Week 48 analysis-population criteria is also not reported, so enrollment should not be assumed to be the endpoint denominator.

Although secondary viral-load outcomes and broader safety and biomarker assessments are described, their detailed results are not reported in the registry record. A full statistical analysis plan, multiplicity procedures, interim analyses, missing-data methods, and sensitivity analyses are not reported in the registry record. The record also does not provide event-level detail or a death count for the safety outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients — NCT01199939.
• Registry record last updated 2013-12-04; status last verified 2013-10.
• Results first posted 2013-12-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase II study was a multicenter, open-label, single-arm evaluation of once-daily etravirine 400mg, darunavir 800mg, and ritonavir 100mg for 48 weeks in adults with HIV described as early treatment-experienced. The registry lists enrollment as 54 and identifies confirmed virologic response at Week 48 as the primary endpoint, defined as confirmed HIV-1 RNA below 50 copies/mL.

The registry record does not report the primary response count, its analysis denominator, or an estimate with statistical uncertainty. It reports 3 participants with serious adverse events and 28 with other adverse events, each among 54 at risk. The record’s design supports description of one treatment group, not a randomized comparison.