Dolutegravir/Rilpivirine, Antiretroviral Efficacy Study Using Real-world Data in Subjects With Human Immunodeficiency Virus (HIV)-1: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dolutegravir/Rilpivirine, Antiretroviral Efficacy Study Using Real-world Data in Subjects With Human Immunodeficiency Virus (HIV)-1 (NCT03518060), a registered phase not stated study. The primary outcome is Number of Participants With Sustained Virologic Suppression at Year 3.

2. Clinical Question

3. Trial Design

This was a prospective, non-interventional, single-arm, multi-center study of JULUCA use in routine clinical care in Germany. The registry lists the study as completed, with a start date of 2018-06-25 and a primary completion date of 2023-05-14. Enrollment was 209. The study summary describes an initial aim of including approximately 250 participants, but the registry’s enrollment figure is 209.

Participants were virologically suppressed and on stable antiretroviral therapy before switching to JULUCA, the combination of dolutegravir and rilpivirine. The record says treating physicians determined inclusion at their discretion. Follow-up was approximately 3 years, with information collected during routine clinical care. The design therefore describes observation of treatment use in practice, not randomized allocation by the study.

The primary outcome is the number of participants with sustained virologic suppression at Year 3. The registry also lists secondary outcomes concerning suppression at Year 1 and Year 2, low-level viremia, virologic rebound, treatment switch, monitoring measures, serious adverse events, adverse drug reactions, and adherence. There are 13 outcome measures listed in total.

The record does not describe a concurrent control arm or a randomized comparison. It also does not report the detailed statistical analysis plan, sample-size justification, or methods for handling participants who lacked outcome measurements. The posted record contains 0 analysis entries. Consequently, the design and listed outcomes can be described, but a treatment-effect estimate or inferential comparison cannot be reconstructed from the registry information.

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: A total of 209 participants were enrolled in the full analysis set (FAS) from which 9 participants were excluded due to not meeting the eligibility criteria. Therefore, 200 participants formed the modified FAS (mFAS).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the modified Full Analysis Set (mFAS) which included all eligible participants who did not have any violation of inclusion or exclusion criteria which also included screening failures and major protocol deviations.

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 Sustained Virologic Suppression at Year 3, measured over At Year 3.

The primary endpoint is the number of participants with sustained virologic suppression at Year 3. The registry defines suppression as HIV-RNA below 50 copies/mL for at least 6 months. It also counts a result between 50 and 200 copies/mL when the next available measurement, within 120 days, is below 50 copies/mL. A later measurement can serve as the consecutive measurement if it is obtained within that interval. If no subsequent HIV-RNA measurement occurs within 120 days, the outcome is scored as confirmed HIV-RNA of 200 copies/mL or more.

This endpoint uses repeated viral-load measurements to characterize suppression over time rather than relying only on a single reading. In general, requiring persistence or confirmation can help distinguish a sustained pattern from an isolated measurement. The endpoint’s rule for measurements between 50 and 200 copies/mL makes the follow-up measurement relevant to classification.

The registry identifies the endpoint’s timeframe as Year 3 and names the modified Full Analysis Set as the analysis population. However, the number meeting the definition is not reported in the registry record. The record therefore supplies the outcome definition but not the observed endpoint count or an estimate of its uncertainty. Without that result, the endpoint cannot be used to quantify the frequency of sustained suppression among the analyzed participants.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What type of outcome is this?

The primary measure is a count of participants who meet a defined binary classification: each participant either meets the sustained-suppression definition at Year 3 or does not. The registry calls the unit “Participants” and specifies a count of participants as the parameter. This differs from a continuous measure, such as a laboratory value, because the endpoint reports how many people satisfy the rule rather than the average value of their measurements.

In general, a count is most interpretable alongside its denominator and a clear account of who was included. The registry names the modified Full Analysis Set as the primary analysis population, but it does not report the primary count or the denominator used for that result. Enrollment of 209 is reported, but enrollment should not automatically be treated as the number with an evaluable Year 3 outcome. The record does not state the number with available outcome measurements.

How does the endpoint classify suppression?

The definition uses HIV-RNA below 50 copies/mL for at least 6 months. It has a separate confirmation rule for a measurement between 50 and 200 copies/mL: the next available measurement must be below 50 copies/mL and occur within 120 days. If there is no subsequent measurement in that interval, the definition scores the result as confirmed HIV-RNA of 200 copies/mL or more. This is a prespecified classification rule in the endpoint description; the record does not report how many participants fell into each measurement pattern.

In general, a confirmation rule makes the timing and availability of follow-up measurements part of outcome classification. That can make missing follow-up clinically and analytically relevant. The registry states how one particular missing subsequent measurement is handled when the initial result is between 50 and 200 copies/mL. It does not provide a broader account of missing Year 3 data, missingness in other measurement patterns, or sensitivity analyses.

What can be inferred from the design?

This study is prospective and non-interventional, with one treatment group and no described comparator. In general, prospective follow-up can define when outcomes are assessed, while non-interventional care reflects treatment decisions made in clinical practice. However, physician discretion and the absence of a concurrent comparison group limit causal interpretation. There is no randomized allocation described, and no direct contrast is reported against another regimen or against a control condition.

For a binary outcome, an analysis might report the count meeting the criterion, the number assessed, and an interval expressing uncertainty. These are general statistical reporting concepts, not methods confirmed for this study. The registry does not report a confidence interval method, a regression model, covariate adjustment, or a hypothesis test for the primary endpoint. It lists 0 analysis entries, so no inferential analysis is available to interpret from the record.

What does the record say about precision?

A confidence interval, in general, describes a range of values compatible with an estimate under the assumptions of the analysis. Its width reflects precision: broader intervals indicate less precision than narrower intervals. No primary estimate or interval is reported in the registry record, so the precision of the Year 3 suppression result cannot be assessed. The enrollment figure alone does not establish the precision of a particular endpoint because the outcome denominator and result are not reported.

The registry also does not state a sample-size justification or a target precision for the primary outcome. It describes an aim to include approximately 250 participants and reports enrollment of 209, but does not connect those figures to a power calculation or planned statistical threshold. No sample-size calculation should therefore be interpreted as the study’s own justification or as evidence about the observed outcome.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary Year 3 suppression outcome and secondary outcomes at Year 1 and Year 2, as well as viremia, rebound, treatment changes, monitoring, safety, and adherence measures. The record does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment for multiple comparisons. It also does not report inferential analyses for those outcomes; the record lists 0 analysis entries. As a result, the statistical status of any comparisons across outcomes or time points is not described.

In general, examining multiple outcomes can increase the chance of apparently notable findings when each is tested separately. A prespecified strategy can clarify which findings are confirmatory and how uncertainty is handled. That is a general consideration, not a description of this study’s methods; the multiplicity plan is not reported in the registry record.

The primary population is identified as the modified Full Analysis Set, described as eligible participants without inclusion or exclusion violations and including screening failures and major protocol deviations. The wording does not explain how those groups were handled in the endpoint calculation. The number in that population and the number with observed Year 3 measurements are not reported.

The registry provides a specific classification rule for the absence of a subsequent measurement within 120 days after an HIV-RNA result between 50 and 200 copies/mL. It does not report broader missing-data procedures, the extent or reasons for missing outcomes, or sensitivity analyses. Thus, the implications of missing follow-up for the primary endpoint cannot be fully assessed from the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (1.5%), dyspnoea (1.5%), lymphadenopathy (1.0%), road traffic accident (1.0%), mitral valve repair (1.0%).

For participants who received JULUCA, the registry reports 200 participants at risk for serious adverse events and 52 affected. It also reports 200 participants at risk for other adverse events and 41 affected, and records 1 death. These are descriptive counts; the registry record does not provide a comparator group for judging relative frequency between treatments.

The listed serious-event terms include atrial fibrillation and dyspnoea, each reported as 1.5%; lymphadenopathy, road traffic accident, and mitral valve repair, each 1.0%; and angina pectoris, 0.5%. The record does not clarify the denominator for these term percentages in the information. They should therefore be read as listed event-term figures, not as comparative risks or evidence that JULUCA caused an event.

In general, an adverse event occurring during follow-up does not by itself establish that treatment caused it. Interpretation also depends on definitions, exposure time, event ascertainment, and the clinical context. Those details and a comparative safety analysis are not reported in the registry record. The figures describe recorded events in the study group and should not be extended beyond that descriptive role.

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

The study addresses real-world use of a two-drug antiretroviral regimen among participants who were already virologically suppressed on stable therapy before switching. Its prospective, multi-center follow-up in routine clinical care provides a framework for observing outcomes in that setting. The registry defines sustained suppression at Year 3 using HIV-RNA measurements and a confirmation rule, and lists additional outcomes concerning suppression, viremia, treatment, monitoring, safety, and adherence.

The central limitation for interpreting the primary question is that the Year 3 outcome count is not reported in the registry record. There is consequently no reported estimate of how many participants met the definition, no confidence interval describing its precision, and no inferential result to evaluate. A stated endpoint definition is not itself evidence about the observed outcome.

The design also does not establish a treatment contrast. Participants were not described as randomly assigned, and no separate comparator group is reported. Since the switch occurred in routine care at physician discretion, participant selection and clinical circumstances may shape the observed group. Without a comparable control group, the record cannot isolate a treatment effect from other influences or establish what would have occurred under an alternative regimen.

Safety information is similarly descriptive. The record lists serious adverse events among participants who received JULUCA and reports a death, but these figures do not show comparative risk or establish causation. Event-term percentages also need context about their denominator and ascertainment to support stronger interpretation.

In general, observational studies can contribute evidence about use and outcomes in clinical practice, while causal claims require careful attention to comparison groups and confounding. Here, the available registry information supports a description of the study’s aims, population, endpoint definition, and listed safety counts. It does not permit a conclusion about the frequency of the primary outcome or whether outcomes differ from another treatment strategy.

13. Why This Trial Matters Statistically

This study is statistically notable for asking a longitudinal question in routine clinical practice while defining the primary outcome through a rule that uses more than one measurement pattern. The Year 3 endpoint counts participants with sustained suppression, including a confirmation pathway for HIV-RNA between 50 and 200 copies/mL. The timing requirement of a subsequent measurement within 120 days means that follow-up measurement availability is part of how some outcomes are classified.

The design also highlights the distinction between describing real-world outcomes and estimating comparative treatment effects. Prospective follow-up and multi-center routine-care data can describe a group treated in ordinary clinical settings. But because the study is single-arm and non-interventional, its registry record does not supply a concurrent randomized comparator. It therefore cannot, on its own, separate treatment-associated outcomes from differences in who was selected for treatment or other clinical influences.

For biostatistical interpretation, the absence of a posted primary result is consequential. The endpoint, timeframe, and analysis population are named, but the record does not report the count or denominator needed to assess the outcome. Nor does it report an interval or analysis method. This prevents assessment of both the observed frequency and its precision, even though the study is marked completed.

The record also lists multiple outcomes, including results at earlier follow-up times and several safety and treatment measures, while reporting 0 analysis entries. The multiplicity approach and missing-data methods are not reported. These gaps matter because readers need to know which analyses were planned, how outcomes were classified when information was unavailable, and how uncertainty was quantified. The registry information makes the intended clinical question clear, but leaves key elements needed for statistical interpretation unreported.

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 registry’s primary outcome result is not reported, despite the study being marked completed. The record therefore does not give the Year 3 count, its denominator, or a measure of uncertainty. Enrollment of 209 does not establish how many participants contributed to the primary analysis, and the number with an evaluable Year 3 outcome is not reported.

The study is single-arm and non-interventional. No comparator group or randomized treatment allocation is described, and treating physicians chose participants for inclusion at their discretion. This restricts comparative interpretation and leaves the possibility that participant characteristics or clinical decisions influenced who entered the study and what outcomes were observed.

The record describes the modified Full Analysis Set but does not state its size or clarify how screening failures and major protocol deviations were treated in the reported endpoint calculation. Although the suppression definition specifies how to classify one situation without a subsequent measurement within 120 days, broader missing-data methods and sensitivity analyses are not reported.

The registry lists 13 outcome measures and 0 analysis entries. The statistical analysis plan, multiplicity approach, covariate adjustment, confidence interval method, and sample-size justification are not reported in the registry record. The study summary’s aim of approximately 250 participants and the enrollment of 209 do not, by themselves, establish planned precision or statistical power.

Finally, the safety information is descriptive. The record does not report a comparative safety analysis, and the context and denominator for the listed event-term percentages are not stated in the information available. These limitations constrain interpretation to the study description and posted counts rather than comparative or causal conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dolutegravir/Rilpivirine, Antiretroviral Efficacy Study Using Real-world Data in Subjects With Human Immunodeficiency Virus (HIV)-1 — NCT03518060.
• Registry record last updated 2024-10-16; status last verified 2024-10.
• Results first posted 2024-10-16.
• 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

This completed study examined JULUCA use in routine clinical care in Germany among HIV-positive participants who were virologically suppressed on stable antiretroviral therapy before switching. It was prospective, non-interventional, multi-center, and single-arm, with approximately 3 years of follow-up. The registry reports enrollment of 209 participants.

The primary endpoint was the number of participants with sustained virologic suppression at Year 3, classified using HIV-RNA measurements and a specified confirmation rule. The primary result is not reported in the registry record. The record lists 13 outcome measures and 0 analysis entries, and does not report a comparator or detailed statistical analysis plan.

For the JULUCA group, the registry reports 52 participants affected by serious adverse events among 200 at risk and 1 death. These safety figures are descriptive and are not comparative estimates.