Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection (NCT00959894), a na phase 2 study. The primary outcome is The Antiretroviral Activity of Etravirine 400 mg Given Once Daily, With Fixed-dose Truvada Once Daily, Among Treatment-naïve HIV-1 Infected Adults as Measured by the Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24.

2. Clinical Question

This question concerns the observed antiretroviral activity of the combined regimen in the study population, rather than the independent contribution of etravirine. Because all participants received the same study regimen and there was no control arm, the study does not estimate a comparative treatment effect. It also cannot, by itself, separate the effect of etravirine from the effect of fixed-dose tenofovir/emtricitabine or from other influences over follow-up.

The registry lists additional outcomes concerning viral-load thresholds at later time points and changes in CD4+ cell count. It also describes genital-secretion pharmacokinetic and metabolic sub-studies. These aims are distinct from the primary Week 24 question: they concern later viral-load measurements, immune-cell changes, drug levels in genital secretions, and metabolic measures. The record does not report the numerical results for those outcomes in the information available for this analysis.

3. Trial Design

This was a Phase 2, prospective, single-group, open-label study sponsored by the University of North Carolina, Chapel Hill. The registry lists the study as completed, with a start date of 2009-09 and primary completion in 2014-02. Enrollment is listed as 80. The study description identifies the target population as treatment-naïve adults with HIV-1 infection.

Participants received etravirine 400 mg once daily with fixed-dose tenofovir/emtricitabine, described as Truvada one tablet once daily. The registry records no masking and lists allocation as NA. In practical terms, this was not a randomized, masked comparison between treatment groups: the study is described as having a single group, and no concurrent control arm is listed. Consequently, its design addresses outcomes observed during treatment, not whether those outcomes differ from what would have occurred under another regimen.

The primary endpoint was the proportion with HIV-1 RNA <50 copies/mL at Week 24. The endpoint description defines the assessment window as >18 and <30 weeks post-entry. Of 79 participants who initiated study medications, 74 had a Week 24 HIV-1 RNA measurement. The primary analysis is described as intention-to-treat, with missing evaluations counted as failures.

The brief summary also describes a genital secretions pharmacokinetic sub-study and a metabolic sub-study. Their stated purposes were to assess drug levels and HIV-1 RNA in genital secretions, and to learn about body composition, lipid levels, and glucose levels, respectively. The registry record does not report the detailed procedures for these sub-studies, the allocation process beyond its NA listing, or a fuller 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: 80 participants were enrolled, however 1 participant was found to be ineligible on the day of entry and never started study medication (had developed acute renal failure and therefore no longer met eligibility requirements).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of 79 participants who initiated study medications, 74 had a Week 24 HIV-1 RNA measurement. The primary analysis was conducted intention-to-treat, with missing evaluations counted as failure.

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.

Population: All participants who received at least one dose of study medication (etravirine 400 mg given once daily with with one tablet of fixed dose tenofovir/emtricitabine).

6. Primary Endpoint

The registry lists the primary outcome as The Antiretroviral Activity of Etravirine 400 mg Given Once Daily, With Fixed-dose Truvada Once Daily, Among Treatment-naïve HIV-1 Infected Adults as Measured by the Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24, measured over 24 weeks.

The primary endpoint is the proportion of participants with HIV-1 RNA <50 copies/mL at Week 24. It represents the share of the analyzed group meeting a specified viral-load threshold at a defined follow-up point. The endpoint description says the qualifying measurement had to fall within the Week 24 analysis window, defined as >18 and <30 weeks post-entry.

A threshold-based endpoint makes the study question concrete: participants are classified according to whether their measurement is below the stated cutoff during the specified window. The proportion is a summary of how often that criterion was met in the analyzed group. It does not describe the full distribution of viral-load measurements, and it does not indicate how far below or above the threshold any measurement was.

The endpoint is used to describe antiretroviral activity at the specified time point. Its interpretation depends on the population included and the handling of missing measurements. The registry says the primary analysis was intention-to-treat and counted missing evaluations as failures. Of 79 participants who initiated study medications, 74 had a Week 24 HIV-1 RNA measurement.

The registry identifies a 95% confidence interval as the endpoint’s dispersion measure, but does not report the observed proportion or interval bounds in the record. Therefore, the magnitude and precision of the primary estimate cannot be assessed from this record. The endpoint definition alone describes what was intended to be measured; it is not a result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary endpoint: whether a participant had HIV-1 RNA <50 copies/mL during the Week 24 analysis window. The associated unit is a proportion of participants. In general, a binary endpoint reduces an individual measurement to whether it meets a predefined criterion. The resulting proportion is easy to interpret as a frequency in the analyzed population, but it does not preserve all information in the underlying continuous measurement. In this study, the record does not report the observed proportion.

What does the confidence interval convey?

The primary endpoint lists a 95% confidence interval as its measure of dispersion. In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions and method used to calculate it. A narrower interval indicates greater precision than a wider interval, while neither interval width nor the confidence level removes design limitations or proves a causal effect. The registry record does not report the interval bounds or the method used to calculate them, so its precision cannot be evaluated.

How does the analysis rule treat missing measurements?

The endpoint description calls the primary analysis intention-to-treat and explicitly states that missing evaluations were counted as failures. In general, intention-to-treat analyses aim to retain participants in the analysis according to the assigned or planned study group, rather than restricting analysis only to participants who completed treatment or follow-up. In this single-group study, the stated rule means missing Week 24 evaluations do not count as meeting the endpoint. The record says 79 participants initiated medication and 74 had a Week 24 HIV-1 RNA measurement. It does not report reasons for missing measurements or any sensitivity analysis using alternative assumptions.

Why does the study design affect interpretation?

A single-group study describes outcomes within the group receiving the regimen. General statistical interpretation distinguishes such a within-group description from a comparative treatment effect. Without a concurrent comparator, differences from baseline or a threshold response cannot by themselves show what would have happened under another treatment or without the study regimen. Open-label status also means masking is listed as none; the record does not detail how that feature affected measurement or care. No randomized allocation is described: allocation is listed as NA.

These design features do not make a descriptive endpoint meaningless. They define what it can answer. The primary endpoint can characterize the proportion meeting the viral-load criterion at the specified follow-up point if the estimate is reported. It cannot, through this design alone, attribute that proportion to etravirine rather than the combined regimen, participant characteristics, or other influences.

What does over-dispersion mean in general?

For count or proportion data, a simple statistical model may assume that variability follows a specified distribution. Over-dispersion means the observed variability is greater than that model expects. If it is ignored, uncertainty can be understated and confidence intervals or tests may be too optimistic. This is a general statistical concept; the registry record does not state that over-dispersion was assessed or that a model requiring such an assessment was used for the primary endpoint.

Can the estimate be recalculated?

The primary outcome estimate is not reported in the registry record, so an unadjusted recalculation from posted summary statistics is not available. The registry gives a confidence-interval label but not the result or its bounds. No p-value for the primary endpoint is reported in the record. The analysis count is listed as 0, and the record does not provide a fuller statistical methods description or a detailed statistical plan.

The record lists sample-size planning illustrations based on an observed effect and specified assumptions, including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning illustrations, not observed power. The trial itself is described as single-group, so the equal-allocation, two-arm planning assumption should not be read as the actual study design. No sample-size justification for the trial is reported in the registry record.

The Week 24 endpoint is one among a broader set of outcomes. In general, when researchers examine multiple outcomes or time points, the chance of at least one apparently notable result can increase if no adjustment or prioritization is used. The registry does not report a multiplicity strategy or a statistical plan describing how outcomes were prioritized. No adjustment method should therefore be presumed.

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("Etravirine 400 mg Once Daily")
n      <- c(79)
events <- c(1)
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  Etravirine 400 mg Once Daily  79  1  1.3  0.0  6.9  0.2  6.8  0.3  6.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the Week 24 proportion with HIV-1 RNA <50 copies/mL as the primary endpoint. It also lists secondary outcomes concerning viral-load thresholds at Week 48 and Week 96, a different viral-load cutoff at several time points, and changes in CD4+ cell count at multiple time points. The record does not report a multiplicity adjustment strategy, the order in which secondary outcomes were tested, or how results across these outcomes were intended to be interpreted. These details are not reported in the registry record.

In general, multiplicity arises when multiple hypotheses, outcomes, or time points are examined. Without a prespecified strategy, the chance of finding at least one result that appears statistically notable can rise. Possible approaches include defining a primary endpoint in advance, controlling an overall error rate, or treating secondary analyses as exploratory. Which approach was planned for this study is not reported in the registry record, so none should be attributed to it.

For the primary endpoint, the registry states that missing evaluations counted as failures in an intention-to-treat analysis. It reports that 79 participants initiated study medications and 74 had a Week 24 HIV-1 RNA measurement. The record does not explain why some measurements were unavailable, give further detail on the analysis population, or report sensitivity analyses that use alternative assumptions about missing outcomes. In general, counting missing outcomes as failures is a defined analysis rule, but its implications depend on why outcomes are missing and how missingness relates to the outcome.

The registry does not describe interim analyses, stopping rules, a sample-size justification, or a complete statistical analysis plan. These items are not reported in the registry record. Because the numerical primary result is also absent, the record cannot support a statistical assessment of the result’s magnitude, precision, or relationship to any multiplicity procedure.

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: vomiting (1.3%), viral gastroenteritis (1.3%), colitis (1.3%), renal impairment (1.3%), meningitis (1.3%).

The registry’s adverse-event summary lists 79 participants at risk for serious adverse events, with 12 affected, and 79 at risk for other adverse events, with 17 affected. These are separate summary categories. The record does not explain whether participants affected in one category also appear in the other, so the counts should not be combined or treated as counts of unique individuals.

The listed serious adverse-event terms are vomiting, viral gastroenteritis, colitis, renal impairment, meningitis, and cellulitis. Each term is reported at 1.3%. The registry does not give additional event-level detail in the information available for this analysis, such as timing, duration, severity grading, or whether the events were considered related to treatment. The death count is not reported in the registry record.

These figures are descriptive summaries from a single-group study. In general, an at-risk count indicates the group used as the denominator for an adverse-event summary, while an affected count indicates the number reported as having the event category. Such counts can describe what was recorded during the study, but without a concurrent comparator they do not establish a relative difference in risk between treatments. The registry record does not support attributing the listed events to etravirine or estimating comparative safety.

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

The record defines a study of etravirine 400 mg once daily given with fixed-dose tenofovir/emtricitabine in treatment-naïve adults with HIV-1 infection. Its primary question concerns the proportion of participants with HIV-1 RNA <50 copies/mL at Week 24. The endpoint window and missing-data rule are described, and the record reports how many participants initiated medication and how many had a Week 24 measurement.

However, the primary response proportion and its 95% confidence interval are not reported in the registry record. The result therefore cannot be quantified, and its statistical precision cannot be assessed. The endpoint definition does not itself show how many participants met the criterion. The same limitation applies to the listed secondary efficacy outcomes: their definitions appear in the record, but numerical results are not reported in the information available for this analysis.

Even if a response estimate were available, its interpretation would remain descriptive because the study has a single group and no concurrent comparator. An observed proportion could describe outcomes among participants receiving the combined regimen, but it could not establish how outcomes would differ under another regimen. Nor could it isolate etravirine’s contribution from the co-administered fixed-dose medicines.

The safety summaries describe affected participants and listed serious-event terms, but they do not establish comparative risks or treatment causation. In general, event reports from an uncontrolled study can contribute descriptive information, while causal attribution requires evidence beyond temporal occurrence. The record does not provide the details needed to assess event timing, treatment relationship, or a comparison group.

Accordingly, the registry supports understanding what investigators planned to measure, how they defined the primary endpoint, and how missing Week 24 assessments were handled. It does not support a numerical conclusion about the primary outcome, a comparative efficacy claim, or a conclusion about comparative safety. These boundaries reflect what is documented in the registry record, not a judgment about whether the regimen is appropriate for any individual.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and reporting determine the scope of a result. The study asks a focused, threshold-based question at Week 24, but its single-group structure means the endpoint is descriptive rather than a randomized comparison. Recognizing that distinction prevents a within-group response proportion from being interpreted as a treatment effect relative to an alternative.

The record also illustrates why an endpoint definition and an endpoint result are different things. It specifies HIV-1 RNA <50 copies/mL, the Week 24 analysis window, a 95% confidence interval, and a rule counting missing evaluations as failures. Yet the numerical estimate and interval are not reported in the registry record. Without them, readers cannot evaluate either the observed response frequency or the estimate’s precision.

Missing measurements matter because analysis rules shape what a reported proportion represents. The registry’s failure rule is explicit, and the record notes that 79 participants initiated medication while 74 had a Week 24 measurement. That information clarifies the endpoint’s context, but does not replace a complete outcome report or explain why measurements were unavailable.

The record also lists outcomes across several viral-load cutoffs and time points, along with CD4+ cell-count outcomes. Such a collection makes clear why a statistical plan for prioritizing outcomes and handling multiplicity can aid interpretation. The registry does not report that plan. Readers should not infer a correction method or an analysis hierarchy that is not recorded.

Finally, the sample-size planning assumptions listed in the registry should not be confused with the actual single-group study design or with observed power. Planning calculations answer hypothetical design questions under assumptions; they do not supply evidence about the outcome. Taken together, these features make transparent reporting of the estimate, uncertainty, analysis population, and analysis plan especially important for interpreting the study.

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 main limitation for interpreting the primary outcome is that the registry record does not report its numerical estimate or 95% confidence interval. Although the endpoint definition, analysis window, and missing-data rule are recorded, they do not reveal the proportion meeting the endpoint or its precision. Numerical results for the listed secondary efficacy outcomes are also not reported in the information available for this analysis.

The study is single-group and open-label, with no concurrent comparator listed. This design can describe outcomes among participants receiving the combined regimen, but cannot provide a like-for-like estimate of the difference from another regimen. It also cannot separate the contribution of etravirine from that of fixed-dose tenofovir/emtricitabine. Allocation is listed as NA, and the registry does not describe a randomized comparison.

The record says that 79 participants initiated study medications and 74 had a Week 24 HIV-1 RNA measurement. Missing evaluations counted as failures in the primary intention-to-treat analysis. Reasons for missing measurements, additional missing-data analyses, and further details about the analysis population are not reported in the registry record. Without those details and the numerical result, readers cannot assess how missingness may have influenced the estimate.

The registry does not report a full statistical analysis plan, a sample-size justification, interim analyses, or a multiplicity strategy. It also does not provide detailed results for the genital-secretion pharmacokinetic or metabolic sub-studies in the information available for this analysis. Safety summaries lack event-level details and a comparator; the death count is not reported in the registry record. These gaps limit assessments of precision, robustness, comparative interpretation, and the context of reported adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection — NCT00959894.
• Registry record last updated 2016-06-06; status last verified 2016-04.
• Results first posted 2015-05-13.
• 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 2 study was a prospective, open-label, single-group study in treatment-naïve adults with HIV-1 infection. The regimen was etravirine 400 mg once daily with fixed-dose tenofovir/emtricitabine. The registry lists enrollment of 80 and reports that 79 participants initiated study medications.

The primary endpoint was the proportion with HIV-1 RNA <50 copies/mL in the Week 24 analysis window. The primary analysis is described as intention-to-treat, with missing evaluations counted as failures; 74 participants had a Week 24 HIV-1 RNA measurement. The numerical endpoint result and 95% confidence interval are not reported in the registry record.

The registry also lists secondary viral-load and CD4+ cell-count outcomes, genital-secretion pharmacokinetic and metabolic sub-studies, and adverse-event summaries. The single-group design does not provide a randomized comparison, and the record does not report a detailed statistical plan or numerical results for the other efficacy outcomes.