Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N (NCT05349838), a randomized phase 3 study. The primary outcome is Number of Participants With and Without Virological Suppression.

2. Clinical Question

The registered question concerns a treatment switch in a particular clinical context: participants were already virologically suppressed, had a history of NNRTI treatment failure, and had the K103N mutation. It is not a comparison in an unselected HIV-1 population, nor does the record describe a study of starting treatment in participants who were not already suppressed.

The regimen contrast changes over time. During the first 48 weeks, the groups were assigned to the fixed-dose combination or to continued current ART. The continued-ART group was then scheduled to switch to dolutegravir/rilpivirine for the next 48 weeks. Thus, the primary endpoint is specified at 48 weeks, while the title and design describe evaluation over 96 weeks. The record does not report a 96-week primary comparison.

The brief summary also describes interest in tolerability, quality of life, blood-cell and laboratory measures, drug concentrations, and cell-associated virus. Those interests provide context, but they do not substitute for numerical results. The main registry question can be stated precisely; whether the observed data support a particular answer cannot be assessed from the posted primary outcome information.

3. Trial Design

This is a phase 3, randomised, open-label, parallel-group switch study listed as completed, with an enrollment of 140. The title describes it as multicentre. Participants were assigned either to the dolutegravir/rilpivirine fixed-dose combination regimen or to continued ART. The record does not report the randomisation sequence method, allocation concealment procedures, or the number assigned to each group.

In the DTG/RPV group, participants were to take a combined dolutegravir 50 mg/rilpivirine 25 mg tablet orally once daily. In the continued-ART group, participants were to remain on their current boosted PI regimen or other antiretroviral combination for 48 weeks, then switch to the fixed-dose combination for 48 weeks. This planned sequence is important when interpreting later observations: after the initial 48 weeks, the groups no longer represent continuing exposure to two distinct assigned regimens.

The study had no masking. Participants and clinical teams therefore knew the assigned treatment. That feature does not alter the definition of the primary endpoint, which is based on HIV RNA, but knowledge of assignment can matter for outcomes that depend on participant reports, clinical decisions, or assessment. The registry record does not describe additional measures to address such potential influences.

The primary endpoint is listed at 48 weeks as the number of participants with and without virological suppression. Suppression is defined as HIV RNA <50 copies/ml. The record lists 32 outcome measures overall and names several secondary outcome topics, including virological status, blood-cell counts, sodium, bilirubin, and alanine aminotransferase. It does not provide numerical results for the primary endpoint or a statistical comparison between groups.

The enrollment total describes the study as registered; it should not be treated as the number evaluated for the primary endpoint in either group. The outcome-specific denominators, analysis population definitions, and disposition of participants are not reported in the registry record. Nor is the protocol’s sample-size justification reported. The posted planning assumptions describe an illustration based on an observed effect, not the trial’s own design or observed power.

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: Of 176 participants that were screened for the study, 140 met eligibility criteria and were randomised to the study.

Overall Study

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 and Without Virological Suppression, measured over 48 weeks.

The primary outcome is a count of participants classified with or without virological suppression at 48 weeks. Suppression is defined in the registry as HIV RNA <50 copies/ml. The endpoint therefore describes a binary status at a specified assessment time: a participant either meets that threshold or does not. It is not a measure of the size of the viral-load change, the time taken to reach suppression, or the duration of suppression.

A binary virological endpoint is useful because it expresses whether participants meet a clinically interpretable laboratory threshold at the assessment time. Counts can be compared between assigned groups to describe the proportion meeting the definition, provided the relevant group denominators and analysis approach are clear. The record gives the endpoint definition but does not report its counts, denominators for the primary analysis, or a treatment-effect estimate. No conclusion about the comparative results can therefore be drawn from the endpoint description alone.

General statistical explanation: A threshold simplifies a continuous measurement into categories. This can make a result easier to communicate, but it also means that values on the same side of the threshold are grouped together even if their exact viral loads differ. Results near a cutoff can also depend on measurement and classification rules. The registry record does not describe additional rules for handling values at the threshold, missing measurements, or repeat assessments.

The 48-week endpoint belongs to the initial period in which the assigned regimens differ. Although the study description covers 96 weeks and the continued-ART group was scheduled to switch after 48 weeks, the registry record does not report a 96-week primary endpoint result. The primary outcome should therefore be interpreted according to its stated 48-week timeframe, not as a summary of all follow-up.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design identifies a randomised comparison, a binary primary outcome, and a defined assessment time. It does not give enough detail to reconstruct the analysis. The registry record does not report the primary group counts, a treatment-effect estimate, confidence limits, the test used, or the analysis population. The distinctions below explain how such elements are generally interpreted; they are not claims about methods used in this trial unless explicitly stated in the record.

What randomisation contributes

General statistical explanation: Randomisation assigns participants to study strategies by chance. When implemented appropriately, it helps make the groups comparable at the point of assignment, including for factors that may not have been measured. It does not guarantee identical groups, prevent deviations from assigned treatment, or resolve missing outcome data. The record states that allocation was randomised, but the sequence-generation and allocation-concealment procedures are not reported. Those details matter when assessing how assignment was implemented.

This is a parallel-group design during the initial treatment period: participants were assigned to one of two strategies rather than each participant being assigned to both strategies at the same time. The open-label designation means masking was absent. Randomisation addresses some sources of confounding, whereas lack of masking can still affect co-interventions, reporting, or outcome assessment. The primary endpoint’s laboratory definition may reduce some subjectivity, but it does not establish that laboratory handling or endpoint classification was blinded.

How a binary endpoint is analysed

General statistical explanation: For a binary outcome, the observed data are commonly represented by the number meeting the outcome definition and the number evaluated in each group. A comparison can then be expressed on different scales, such as a difference in proportions or a ratio of proportions. Each scale answers a slightly different question. The registry record reports the outcome as participant counts with and without suppression, but does not state which contrast or model was used. No effect scale should be attributed to the trial without a reported analysis.

The denominator is essential. If some participants lack a 48-week measurement, results may depend on whether the analysis includes only those assessed, treats missing values according to a prespecified rule, or uses another method. These approaches can answer different questions and may rely on different assumptions. The registry record does not report the amount or handling of missing primary outcome data, so the effect of missingness cannot be evaluated.

Uncertainty and statistical evidence

General statistical explanation: A confidence interval gives a range of values compatible with the data and the chosen method, under its assumptions. Wider intervals generally indicate less precision than narrower intervals. A p-value is calculated relative to a null hypothesis and a specified statistical procedure. Neither quantity is reported for the primary comparison in the registry record. In their absence, readers cannot determine the estimated direction, the precision, or the statistical evidence for a difference.

Even if a p-value were reported, it would not establish whether the result was practically important. The estimate, its uncertainty, the endpoint definition, and the clinical context all matter. A non-significant test would not by itself establish equivalence; that conclusion ordinarily requires a prespecified margin and an appropriate analysis. The registry record does not report such a margin or a non-inferiority or equivalence analysis.

Planning illustrations are not trial results

The planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of an observed effect. For non-time-to-event outcomes, the stated convention is participants per arm for 80% power or 90% power; time-to-event planning is described in terms of total events. These are planning conventions, not observed results, and do not establish the power achieved by the completed study. The registry record does not report the trial’s own sample-size justification. No numerical planning outputs are reported in the registry record.

General statistical explanation: Planning calculations depend on assumptions about the outcome rate or effect size, variability, allocation, significance level, and analysis method. If the assumed effect differs from the true effect, the planning result can differ from what the study would achieve. “Observed power” calculated after seeing a result does not add a separate measure of evidence beyond the estimate and its uncertainty. Planning illustrations are best read as conditional scenarios, not as guarantees.

Why dispersion and model choice matter

General statistical explanation: Over-dispersion arises when observed variability is greater than a model expects. It can make standard errors too small if a model assumes less variation than is present, which in turn can make confidence intervals too narrow and tests too optimistic. The registry describes a binary participant-count endpoint and does not report a dispersion estimate or model. Over-dispersion is therefore a general modelling consideration, not a reported finding for this trial.

Finally, the planned treatment sequence changes after 48 weeks. A 48-week comparison concerns the two initially assigned strategies; a later comparison would have to account for the switch in the continued-ART group. The registry record does not report the later comparative analysis method. Without the numerical endpoint data and analysis details, statistical interpretation should remain limited to the registered design and definition.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 32 outcome measures and describes several secondary outcome topics, including virological status, blood-cell counts, sodium, bilirubin, and alanine aminotransferase. When a study evaluates multiple outcomes, time points, or comparisons, the chance of at least one apparently notable result can increase if each is assessed separately. General statistical explanation: A multiplicity plan can specify which outcomes are confirmatory, how tests are ordered, or whether significance thresholds are adjusted. The registry record does not report a multiplicity strategy, so it is not possible to determine how the family of outcomes was handled.

The primary outcome is specified at 48 weeks. The registry record does not report whether other endpoint time points were included in the primary analysis, how secondary outcomes were formally tested, or whether any analyses were prespecified. A list of outcomes is not itself evidence that each was analysed or that each carried the same inferential status.

Missing-data methods and analysis populations are also not reported in the registry record. The number enrolled does not establish how many participants had an evaluable 48-week measurement. The record does not describe withdrawals, exclusions, adherence, imputation, or whether the primary analysis followed assignment regardless of treatment changes. These omissions limit assessment of possible bias and of how well the primary analysis represents the randomised groups.

General statistical explanation: Missingness can affect a comparison when the chance of an unavailable measurement is related to participant characteristics or outcomes. Complete-case analyses can be biased under some missingness patterns, while imputation or model-based methods require assumptions of their own. A transparent report typically states the amount of missing data, reasons where known, and the handling method. Those details are not reported for this endpoint.

11. 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: penile neoplasm (2.2%), pancreatitis (2.2%), covid-19 pneumonia (2.2%), atypical mycobacterial infection (2.2%), meningioma (1.1%).

The registry record reports serious adverse event figures for both groups. In the DTG/RPV FDC Regimen group, 12 participants were affected among 95 at risk; in the Continued ART Regimen group, 4 participants were affected among 45 at risk. The record also lists other adverse events: 66 participants affected among 95 at risk in the DTG/RPV group and 19 among 45 at risk in the Continued ART group. Deaths are listed as 0 in each group.

These are reported counts and group-specific at-risk figures, not adjusted comparisons. The registry record does not provide a comparative estimate or uncertainty interval for the safety contrast. The counts alone do not account for differences in follow-up time, participant characteristics, or exposure after the scheduled switch. The continued-ART group’s planned regimen changed after 48 weeks, which is relevant when interpreting safety observations over the full study period.

The record lists the following top serious adverse event terms with their reported percentages: penile neoplasm, 2.2%; pancreatitis, 2.2%; COVID-19 pneumonia, 2.2%; atypical mycobacterial infection, 2.2%; meningioma, 1.1%; and pachymeningitis, 1.1%. The listing does not assign these terms to a particular group in the information, and it does not establish causality. A serious adverse event is not necessarily caused by the study treatment.

The registry record does not provide further details on event timing, recurrent events, severity beyond the serious classification, or attribution. The figures therefore describe reported safety counts but do not by themselves establish a comparative safety profile.

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

The registry record supports a clear description of the research question: a randomised, open-label switch study compared an initial dolutegravir/rilpivirine strategy with continued current ART in antiretroviral treatment-experienced participants who were suppressed and had the K103N mutation. It defines the primary endpoint as suppression at 48 weeks, using HIV RNA <50 copies/ml.

It does not provide the primary outcome counts or a comparative estimate. The posted information therefore cannot establish whether the groups had similar or different suppression results, how large any difference was, or how precisely it was estimated. No conclusion about efficacy or lack of efficacy follows from the endpoint definition alone. The absence of a reported estimate is not evidence of no effect.

The enrollment of 140 and the serious adverse event counts provide context about the registered study, but neither substitutes for the missing efficacy analysis. Likewise, the study’s phase, randomisation, and endpoint definition describe design features rather than the observed treatment effect. Interpretation requires the actual outcome data, analysis population, and methods for handling missing measurements.

General statistical explanation: A result that does not demonstrate a statistically detectable difference is not automatically evidence that two strategies are equivalent. Equivalence or non-inferiority requires an appropriate design, a prespecified margin, and an analysis suited to that question. The registry record does not report such a margin or the primary comparison results.

The scheduled switch in the continued-ART group also limits what a longer-term comparison would represent. After 48 weeks, both groups were to receive the fixed-dose combination, so later observations would not preserve the initial contrast between continuing current ART and switching immediately. The registry record does not report a comparative 96-week primary result.

These limitations concern what can be inferred from the registry record, not what the complete study dataset might contain. The posted record is informative about the intended design and outcome definitions, but the missing efficacy results prevent a statistical assessment of the main treatment question.

13. Why This Trial Matters Statistically

This study raises a useful statistical question about a treatment switch in a defined population rather than a broad comparison across all people with HIV-1. Participants were described as treatment-experienced, virologically suppressed, and carrying the K103N mutation after previous virological failure with NNRTIs. Defining the population matters because the relevance of a treatment comparison depends on who was studied and the clinical context of the switch.

The endpoint is also specific: a participant count classified by HIV RNA <50 copies/ml at 48 weeks. That definition makes the outcome understandable, but it does not communicate the full distribution of viral-load measurements or the exact number evaluated. Group denominators, outcome counts, and an uncertainty estimate are needed to understand the comparative result. The registry record does not report those primary efficacy results.

The design’s timing matters statistically. The first 48 weeks compare two assigned strategies, while the continued-ART group was scheduled to switch after that point. A later assessment would therefore involve treatment convergence rather than a sustained contrast between the original regimens. The record distinguishes the 48-week primary endpoint from the 96-week study period, but does not provide a later comparative primary result.

The open-label design and the mixture of objective and participant-centred secondary topics also illustrate why outcome type matters. Laboratory-defined outcomes may be less directly affected by expectations than self-reported outcomes, while still depending on assessment and missing-data procedures. The registry record does not report those procedures in detail.

Finally, the study underscores a basic reporting principle: design information cannot replace results. Randomisation, an explicit endpoint, and a defined treatment sequence help readers understand what comparison was intended. Without the observed primary outcome and its uncertainty, however, the central statistical question remains unanswered by the registry record.

14. 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 statistical interpretation is that the registry record does not report numerical results for the primary 48-week endpoint. There are no group counts with or without suppression, no primary analysis denominators, and no comparative estimate or uncertainty interval. The primary treatment question therefore cannot be answered from the posted results.

Some design details are also absent. The record does not report the randomisation sequence method, allocation concealment, protocol sample-size justification, analysis populations, or the statistical method used for the primary comparison. It does not describe missing outcome data, participant withdrawals, adherence, or how treatment changes were incorporated into analysis. These details are needed to assess implementation and the robustness of an estimate.

The study was open-label, and the planned treatment strategies differed only during the initial 48 weeks; the continued-ART group was scheduled to switch thereafter. The record does not give outcome-assessment procedures that would clarify whether laboratory classifications were made without knowledge of assignment. The later switch also means that longer-term outcomes would not represent a persistent comparison of the original assigned regimens.

The record lists multiple outcome measures but does not report the multiplicity plan or the inferential role of each secondary outcome. It also gives serious adverse event counts and top event terms without comparative estimates, event timing, or attribution information. These safety figures should not be interpreted as proof that an event was caused by a regimen or as a fully adjusted comparison.

These are limitations of the information reported in the registry record. They do not establish that the complete study report lacks additional methods or results; they indicate that those details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N — NCT05349838.
• Registry record last updated 2024-12-24; status last verified 2024-11.
• Results first posted 2024-12-24.
• 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.

18. Record Summary

NCT05349838 is a completed phase 3, randomised, open-label, parallel-group switch study with enrollment of 140. It evaluated dolutegravir 50 mg/rilpivirine 25 mg as a once-daily fixed-dose combination in antiretroviral treatment-experienced participants with HIV-1, virological suppression, previous NNRTI failure, and the K103N mutation.

The comparator group continued its current boosted PI regimen or other antiretroviral combination for 48 weeks, then switched to the fixed-dose combination for 48 weeks. The primary outcome was the number of participants with and without virological suppression at 48 weeks, defined as HIV RNA <50 copies/ml.

The registry record does not report the primary outcome counts, a comparative efficacy estimate, or its uncertainty. Serious adverse event counts are listed as 12 among 95 at risk in the DTG/RPV group and 4 among 45 at risk in the Continued ART group; deaths are listed as 0 in each group. The registry record does not report the primary analysis methods, missing-data handling, or the protocol’s sample-size justification.