Bictegravir/Emtricitabine/Tenofovir Alafenide Plus Doravirine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bictegravir/Emtricitabine/Tenofovir Alafenide Plus Doravirine (NCT04538040), a na phase 4 study. The primary outcome is Viral Suppression.

2. Clinical Question

The study concerns maintenance of viral suppression after changing the regimen, rather than a comparison between randomized groups. Its brief summary proposes that participants with prior NUC or NNRTI resistance, but not resistance to rilpivirine or doravirine, would maintain suppression after the switch. That statement is the study hypothesis, not a reported finding.

The registry record also identifies secondary topics: tolerability, body mass index, work productivity and activity, pharmacokinetic assessment, adverse events, and wellbeing. Their presence indicates areas the study intended to assess; it does not establish that results for those outcomes are available. The posted record does not give a numerical primary outcome, an estimate of the proportion suppressed, or an uncertainty interval.

3. Trial Design

This is a Phase 4, open-label, single-group study with no allocation to different treatment arms. The registry lists enrollment of 20 and status as completed. Its dates are December 19, 2019, for study start and November 11, 2021, for primary completion.

The official study description concerns male participants older than 45 with multidrug-resistant HIV and documented suppression on the existing regimen. Participants switched from rilpivirine/emtricitabine/tenofovir alafenamide plus dolutegravir to bictegravir/emtricitabine/tenofovir alafenamide plus doravirine. The listed intervention is the switch regimen, taken orally once per day.

The brief summary calls the proposal an open-label observational trial and describes it as a non-inferiority switch trial. The registry also lists a drug intervention and a single-group model. These descriptions establish that the posted record does not describe a randomized, concurrent-control comparison. It does not give further detail on how observations were collected or how the analysis was conducted.

The brief summary says the study was expected to involve approximately 30 patients, including a pharmacokinetic arm of approximately 10 patients. The enrollment field, in contrast, reports 20. These are distinct descriptions: the former is the summary’s expectation and the latter is the registry’s enrollment figure. The record does not explain the difference or report how many participants contributed to each outcome.

The registry describes the study as designed for non-inferiority, but the non-inferiority margin, sample-size justification, analysis populations, and statistical plan are not reported in the registry record. The posted results list no analyses. Consequently, the design description gives context for the intended question but does not supply the information needed to evaluate a formal non-inferiority analysis.

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

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 Viral Suppression, measured over 48 Weeks.

The primary outcome is described as the percentage of participants with HIV viral load below the stated thresholds, < 50 and < 200 copies per mL, at 48 weeks. It is a binary outcome at the participant level: a participant’s viral-load measurement is classified in relation to the specified threshold, and the result is intended to express the proportion meeting the endpoint. The registry does not explain how the two thresholds are combined or reported.

Viral suppression is used as the primary measure because the study’s stated question is whether suppression is maintained after the regimen switch. The two thresholds represent different levels of viral-load classification in the endpoint description. They should not be treated as interchangeable without knowing how the protocol or analysis defined them.

The endpoint is a planned measure, not a reported finding in this record. No percentage, participant count meeting either threshold, confidence interval, or statistical test result for the primary outcome is reported in the registry record. Thus the endpoint definition identifies what was intended to be assessed, but it does not show the observed suppression result or its precision.

In general, a percentage is easier to interpret when its numerator, denominator, assessment time, and handling of missing measurements are clear. The record gives the assessment time and overall enrollment, but does not report the primary outcome numerator or analysis denominator, nor how missing viral-load measurements were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available in the registry is limited. It identifies a single-group study, describes a binary percentage endpoint, and gives a 48-week assessment time. It does not report a statistical analysis plan or any listed outcome analyses. The concepts below explain how such an endpoint is generally interpreted, without implying that a particular method was used in this study.

What does a binary percentage represent?

In general, a binary endpoint places each participant into a category defined by the outcome, such as meeting or not meeting a viral-load threshold. The percentage is the number meeting the definition relative to the number assessed under the analysis rules. To interpret it fully, a reader needs the count meeting the definition and the denominator. The registry defines the threshold-based outcome but does not report these counts for viral suppression.

The description names both < 50 and < 200 copies per mL. The record does not specify whether results were intended to be presented separately for each threshold, whether one was the primary definition and the other supportive, or how measurements at the boundary were treated. Those details are important to reproduce or interpret the endpoint, and are not reported in the registry record.

What does a single-group design allow?

In general, a single-group study can describe outcomes observed among participants who receive the intervention. It does not include a concurrent group that provides a direct estimate of outcomes under an alternative treatment during the same period. In a switch study, outcomes on the prior regimen can offer context, but a within-participant sequence alone does not remove changes over time or other influences on the observed result.

The registry labels this study as single-group and lists no allocation. It describes the intended question as non-inferiority, but a non-inferiority assessment ordinarily requires a specified margin and an analysis comparing the treatment effect with that margin. The margin, comparison method, and inferential results are not reported. The non-inferiority label therefore describes the stated intent, not a verifiable conclusion in the posted record.

How should precision be considered?

In general, a point estimate is the observed result, while an uncertainty interval communicates how much statistical uncertainty surrounds that estimate. For a binary proportion, precision depends in part on the number of participants with evaluable outcomes and the distribution of those outcomes. A larger amount of complete information can generally support a more precise estimate, but enrollment alone does not establish the endpoint denominator or precision.

The registry reports enrollment of 20 but does not report the viral-suppression estimate or an interval. No p-value for the primary outcome is listed. It is therefore not possible to describe statistical precision, assess a threshold-based decision, or distinguish a small estimated effect from a result with substantial uncertainty.

What does the design description not establish?

In general, a label such as open-label describes whether treatment assignment is masked, while a single-group label describes the comparison structure. Neither label supplies the outcome analysis method. The registry says the study was open label and single group, but does not report details of endpoint adjudication, viral-load measurement rules, covariate adjustment, or the statistical model. These should not be inferred from the study title or summary.

The brief summary calls the study an observational trial while the registry lists a drug intervention. The record does not explain this terminology. The most direct design details available are that the study is listed as open label and single group and that participants were to switch regimens. No randomized comparator is listed.

What is the role of planning calculations?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, power, and allocation. It is not an observed outcome and is not a measure of the probability that the study’s conclusion is correct. The registry record does not report the trial’s own sample-size justification or the assumptions used to plan enrollment. Its brief summary gives an approximate anticipated enrollment, while the enrollment field reports the number enrolled. Those figures do not substitute for a documented justification.

The posted record contains no listed analyses for the outcomes. As a result, the available information does not identify whether estimates were adjusted, what inferential procedures were used, or how the intended non-inferiority question was evaluated. Any such methods 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("Biktarvy + Doravirine Switch")
n      <- c(20)
events <- c(20)
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  Biktarvy + Doravirine Switch  20  20  100.0  83.2  100.0  83.9  100.0  83.9  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes covering tolerability, body mass index, work productivity and activity, pharmacokinetic assessment, adverse events, and wellbeing. It does not report which secondary outcomes were formally tested, how they were ordered, or whether any adjustment for multiple testing was planned. No multiplicity strategy is reported in the registry record. Without that information, the status of any possible secondary-outcome findings cannot be assessed as confirmatory or exploratory.

Missing-data handling is also not described. The registry does not state how participants without a viral-load measurement at 48 weeks would be treated, whether missing measurements would be imputed, or whether analyses would use observed cases only. It also does not report the number of participants with missing primary outcome data. These details affect the analysis denominator and interpretation of a percentage.

The record does not define analysis populations, such as whether the primary analysis would include all enrolled participants or a subset defined by treatment exposure or outcome availability. Enrollment of 20 does not establish how many participants contributed to the primary endpoint. No analysis population or participant flow for the primary outcome is reported.

In general, multiplicity concerns arise when many outcomes or comparisons are assessed, because the chance of a nominally notable result can increase across repeated tests. Missing-data methods matter because estimates may be influenced if outcomes are unavailable for some participants. These are general statistical considerations; the record does not provide enough detail to determine how either issue was handled in this study.

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 non-serious adverse event terms

The registry lists one intervention group, with 20 participants at risk for serious adverse events and 0 affected. It also lists 20 at risk for other adverse events and 11 affected, with 0 deaths. These are counts recorded for the listed group; they are not comparative estimates against another treatment group.

The serious adverse-event field reports no affected participants, and the list of top serious-event terms is empty. That does not provide detail about how events were collected, assessed, or classified. For other adverse events, the record gives the number affected but does not list event types, severity, timing, or attribution to treatment. Those details are not reported in the registry record.

In general, an adverse-event count describes events recorded under a study’s reporting definitions. It does not by itself establish causation, and a count from a single group cannot show whether risk differs from another regimen. The figures should therefore be read descriptively and alongside the limits of the posted reporting, rather than as a treatment comparison or a complete safety profile.

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

The registry record documents a completed, open-label, single-group switch study with enrollment of 20. It identifies the intended primary question: the percentage of participants with viral loads below the stated thresholds at 48 weeks after switching to bictegravir/emtricitabine/tenofovir alafenamide plus doravirine. It also provides adverse-event counts for the listed group.

The record does not report the primary viral-suppression result. It therefore cannot show what percentage met either threshold, how many participants contributed to that assessment, or how precisely the result was estimated. Nor does it report the analysis needed to evaluate the stated non-inferiority objective. The design description and hypothesis should not be mistaken for outcome evidence.

The absence of a concurrent comparator limits what can be inferred from a single-group result, even if the outcome estimate were available. In general, observed outcomes after a switch can describe what happened in that study group, but they do not alone establish a difference from continued prior treatment. The non-inferiority margin and analysis approach are not reported, so the intended comparison cannot be reconstructed from the registry entry.

The safety counts indicate that the record lists 0 participants affected by serious adverse events, 11 affected by other adverse events, and 0 deaths. The event descriptions and further safety details are not reported. These counts are descriptive and do not establish comparative risk or treatment causality.

Accordingly, the posted record supports a description of the study design, enrollment, endpoint definition, and listed safety counts. It does not support a conclusion about whether viral suppression was maintained, whether the switch met a non-inferiority criterion, or how the results compare with another regimen.

14. Why This Trial Matters Statistically

This study raises a clear statistical question: how to evaluate a threshold-based viral-suppression outcome after a treatment switch when the design has a single group and the stated objective is non-inferiority. The distinction between describing outcomes and making a comparative claim is central. A single-group percentage can summarize the observed participants, but a non-inferiority conclusion requires a defined margin and an analysis that addresses that objective.

The record also illustrates why an endpoint definition and an endpoint result are different kinds of information. It names the 48-week assessment and the viral-load thresholds, but does not report the observed percentage or its precision. Without the outcome numerator, denominator, and uncertainty estimate, readers cannot judge how much information the study contributed to its primary question.

Enrollment and analysis populations also need to be distinguished. The record reports 20 enrolled, while the brief summary anticipated approximately 30 patients, including a pharmacokinetic arm of approximately 10 patients. The record does not explain the difference or state the primary endpoint denominator. A transparent account of participant flow and missing measurements would help readers understand the basis of an outcome estimate.

Finally, the adverse-event counts are useful descriptive information, but they cannot be interpreted as a comparative safety result in the absence of a control group and event-level detail. Taken together, these features make the record a useful example of how design labels, stated hypotheses, outcome definitions, and posted results each answer different statistical questions.

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 principal limitation for interpreting the primary question is that the registry record does not report the viral-suppression result at 48 weeks. It gives no number meeting the endpoint, no analysis denominator, and no uncertainty estimate. The outcome definition also names two viral-load thresholds without explaining how their results are to be reported or related.

The study is listed as open label and single group, with no concurrent comparator. The record describes a non-inferiority objective but does not report a margin or statistical analysis plan. This prevents assessment of whether the planned objective was met. Further design details, including the method of endpoint assessment and any adjustment for other factors, are not reported in the registry record.

The enrollment field reports 20, whereas the brief summary describes approximately 30 patients as expected, including a pharmacokinetic arm of approximately 10. The record does not reconcile these figures or give participant flow by outcome. It also does not report the number with evaluable viral-load measurements or how missing data were handled.

The safety record gives counts of affected participants but lacks event terms for serious adverse events and further descriptions of other adverse events. Timing, severity, attribution, and methods of collection are not reported. The record lists secondary outcome topics but provides no outcome analyses or multiplicity plan. These omissions limit interpretation of both the primary endpoint and the broader set of intended outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bictegravir/Emtricitabine/Tenofovir Alafenide Plus Doravirine — NCT04538040.
• Registry record last updated 2024-03-05; status last verified 2024-03.
• Results first posted 2024-03-05.
• 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 record describes a Phase 4, open-label, single-group switch study in male participants older than 45 with HIV-1 infection, multidrug-resistant virus, and prior documented viral suppression. Participants were to switch from rilpivirine/emtricitabine/tenofovir alafenamide plus dolutegravir to bictegravir/emtricitabine/tenofovir alafenamide plus doravirine.

Enrollment is listed as 20, with study dates from December 19, 2019, to November 11, 2021, and status marked completed. The primary endpoint is described as viral suppression at 48 weeks using thresholds of < 50 and < 200 copies per mL. The primary outcome result and statistical analysis are not reported in the registry record.

For the listed group, the record reports 0 participants affected by serious adverse events, 11 affected by other adverse events, and 0 deaths. It does not report a concurrent comparator, a non-inferiority margin, missing-data methods, or the primary analysis population.