Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRAL: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRAL (NCT02212379), a na phase 2 study. The primary outcome is Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96.

2. Clinical Question

This question concerns maintenance of viral suppression among people who were already suppressed before changing treatment. It is not a question about achieving initial suppression in people with detectable viral load, nor does the single-group design estimate a comparative effect against continued use of a boosted protease inhibitor regimen.

3. Trial Design

This was a phase II, multicenter, international, nonrandomized, open-label, single-group study. The registry lists raltegravir and etravirine as the intervention and reports enrollment of 170 participants. The intended population was HIV-1-infected people aged at least 45 years who were virologically suppressed and switching from a boosted protease inhibitor-containing regimen. The registry record does not report additional participant characteristics or a detailed account of the treatment-switch procedures.

Participants were followed for 96 weeks. The primary endpoint was the proportion with successful virological suppression at weeks 48 and 96. The registry defines success by the absence of 2 consecutive plasma viral loads >50 copies/mL within 2 to 4 weeks of the dual regimen. Secondary outcomes included therapeutic success and treatment interruption at weeks 48 and 96, virological failure categories, time to virological failure, resistance mutations among those with virological failure, factors associated with viral load >50 copies/mL, and change in total cell-associated HIV-DNA.

The study description says it was designed to show efficacy >90%, assuming a success rate >95%, with 80% power and a 5% type-I error. It states that 160 individuals were required to achieve the objective. These are design statements, not observed findings or evidence that the study achieved a particular power after enrollment. The registry record does not report the detailed sample-size calculation, analysis plan, or reasons for the difference between the required number and the enrollment of 170.

Because there was no randomized comparator, the study estimates outcomes within the treated group. Open-label conduct also means participants and investigators knew the regimen being used. The registry record does not describe masking of outcome assessment.

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: Five patients did not initiate the trial treatment by their own decision, leaving 165 patients for the analysis.

From baseline to week 48

Reasons for not completing this period:

From week 48 to week 96

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 Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96, measured over at week48 and at week 96.

The primary endpoint is the proportion of participants with successful virological suppression at weeks 48 and 96. Success is defined as the absence of 2 consecutive plasma viral loads >50 copies/mL within 2 to 4 weeks of the raltegravir/etravirine regimen. The definition therefore treats a single qualifying measurement differently from consecutive qualifying measurements; it focuses on a confirmed pattern rather than an isolated result.

A proportion is a direct way to describe how often a specified outcome occurs in the group being followed. Reporting it at both weeks 48 and 96 describes suppression at two points during follow-up. It does not, by itself, describe every viral-load measurement between those visits, and the registry record does not explain the assessment schedule or how observations between the stated time points contributed to the endpoint.

The registry reports success of 99.4% at week 48, with a 95% confidence interval of 95.6 -99.9, and 98.7% at week 96, with a 95% confidence interval of 95.0 -99.7. A confidence interval conveys uncertainty around an estimate under the analysis used. The record does not identify how these intervals were calculated or give the numbers of participants included in each endpoint denominator. The endpoint is relevant to the study’s stated aim of assessing maintenance of suppression after a regimen switch, but the single-group design means the percentages are not a randomized comparison with another treatment strategy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what the registry reports from what the study can establish. The primary outcome is a proportion: the number of participants classified as having successful virological suppression relative to the number included in the endpoint analysis. The registry reports the resulting percentages at week 48 and week 96, but does not report either endpoint denominator or the underlying counts. Enrollment is not necessarily the same as the number analyzed at each visit, so enrollment should not be substituted for an unreported analysis denominator.

What does the confidence interval convey?

A confidence interval describes uncertainty around an estimated quantity under a specified statistical procedure. In general, narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. The registry gives 95% confidence intervals for both suppression estimates: 95.6 -99.9 at week 48 and 95.0 -99.7 at week 96. The record does not state the interval method, whether it accounts for any features of the data, or how missing outcome information was handled. The numerical endpoints should therefore be interpreted as reported, without assuming a particular calculation method.

A confidence interval is not a guarantee that the true value lies inside the reported limits, nor does it describe the range of outcomes for individual participants. It also does not establish that a prespecified efficacy threshold has been met unless the analysis and decision rule for that claim are specified. The registry reports no p-value or formal test for the primary endpoint. Its point estimates and intervals can be read descriptively, but the record does not document a hypothesis test against the study’s stated target.

What does the single-group design allow?

In a single-group study, the observed outcomes are summarized among those receiving the intervention. Without a separate comparison group, there is no randomized contrast that estimates how outcomes would have differed under another treatment strategy. Randomization is generally used to balance measured and unmeasured prognostic factors between groups, on average. Since this trial was nonrandomized and single-group, that protection against confounding is not available for a treatment comparison. The registry record does not report an external control or an adjusted comparative analysis.

The study was open-label. In general, knowledge of treatment assignment can influence behavior, follow-up, reporting, or decisions about assessments, depending on the outcome and study procedures. The primary endpoint is based on plasma viral-load measurements, but the registry record does not state whether outcome assessors were masked or describe procedures that could limit assessment bias. These are design considerations, not evidence that bias occurred.

How should the design assumptions be read?

The study description says the design aimed to show efficacy >90%, assuming a success rate >95%, with 80% power and a 5% type-I error, and that 160 individuals were required. A power calculation is a prospective planning exercise based on assumptions about the outcome, target, statistical test, and error rates. It is not a statement about the probability that the trial’s conclusion is correct, and it does not establish the power of the completed study based on observed outcomes. The registry record does not provide the detailed calculation, the exact test, or a formal decision rule. The enrollment of 170 is a reported study characteristic, not evidence by itself that the assumptions were met.

General statistical planning can also be sensitive to the assumed success rate and to the choice of target. If the actual event rate differs from the planning assumption, precision and the probability of meeting a study objective can differ from expectations. The registry record does not report whether the assumptions were revisited or whether any adjustment to the planned analysis occurred. Those details should not be inferred from the posted outcome percentages.

What does the definition of success imply?

The endpoint uses a confirmed pattern: absence of 2 consecutive viral loads >50 copies/mL within 2 to 4 weeks of the dual regimen. As a general principle, requiring consecutive elevated measurements can distinguish confirmed failure from a single elevated measurement. The exact operational implementation depends on the measurement schedule, timing rules, and handling of missed tests, none of which are detailed in the registry record. The stated definition should be kept distinct from secondary outcomes that separately refer to low-grade or high-grade virological failure.

For time-to-event outcomes, general methods account for the timing of an event and may also account for participants whose event status is not observed through the end of follow-up. The listed secondary outcomes include median time of virological failure, but the registry record does not report a result or analysis method for that outcome. It is therefore not possible to describe the event-time estimator, censoring rules, or precision for that measure from this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary endpoint. When many outcomes or repeated assessments are examined, the chance of at least one apparently notable result can increase; statistical methods sometimes address this through a prespecified hierarchy or multiplicity adjustment. The registry record does not report whether multiplicity was considered, whether any outcomes were prioritized beyond identifying the primary endpoint, or whether adjustments were used. No conclusions about multiplicity control can be drawn from the outcome list alone.

The primary outcome is reported at both week 48 and week 96, but the record does not explain whether both times were treated as co-primary, whether one was primary and the other supportive, or how any associated inference was planned. The study description identifies successful virological suppression at weeks 48 and 96 as the primary outcome, while the brief summary describes the primary endpoint as the proportion with virological success at 48 weeks. The registry does not reconcile these descriptions or report a testing hierarchy.

Missing-data handling is not reported in the registry record. It does not state how participants without an assessment at a scheduled time were classified, whether missing viral-load measurements were imputed, or whether analyses used observed cases only. The endpoint denominators and participant flow through follow-up are also not reported. These omissions matter because a proportion depends on who is included in its denominator and how unobserved outcomes are handled.

The analysis populations are not described. The record does not say whether results were based on all enrolled participants, participants who began the regimen, or another defined group. It lists zero analysis records, although narrative outcome results are reported. Without a documented statistical analysis plan or analysis-population definitions, the exact inferential framework and the relationship between enrollment and the reported percentages remain unclear.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: prostatitis (1.8%), stroke (1.2%), hospitalization further diagnosis (1.2%), arthritis (0.6%), delirious (0.6%).

For the raltegravir and etravirine group, the registry reports 165 participants at risk, 26 participants affected by serious adverse events, 23 affected by other adverse events, and 0 deaths. These are reported counts. The registry record does not define the analysis period or explain whether participants could be counted in both the serious and other adverse-event categories, so the counts should not be added or treated as mutually exclusive categories.

The listed serious-event terms and percentages are prostatitis, 1.8%; stroke, 1.2%; hospitalization further diagnosis, 1.2%; arthritis, 0.6%; delirious, 0.6%; and hepatic cytolysis, 0.6%. These are the terms identified as the top serious events in the record, not a complete account of every event or an estimate of comparative risk. The record does not give event-level counts for each term, causal assessments, severity grades beyond the serious classification, or a comparator group.

Adverse-event counts are descriptive safety information. In general, interpreting safety requires attention to how events were defined, collected, attributed, and followed, as well as the population and duration of observation. Those details are not reported in the registry record. Because this was a single-group study, the figures cannot establish how the frequency of events compares with another regimen. The reported 0 deaths is a registry count for this group; it does not imply that other safety outcomes were absent.

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

The posted results indicate that most participants included in the reported analyses met the registry’s definition of virological success at both week 48 and week 96. The estimates are 99.4% and 98.7%, respectively, with the stated 95% confidence intervals. These figures describe outcomes in the study group: virologically suppressed HIV-1-infected people aged at least 45 years who switched from a boosted protease inhibitor-containing regimen to raltegravir plus etravirine.

The findings do not establish that the dual regimen is better, equivalent, or noninferior to another regimen. There was no randomized comparison group, and the registry record does not report a comparative analysis. Nor do the results establish that the same suppression estimates would apply to people who were not suppressed before switching, people below the stated age threshold, or other populations not described in the study eligibility.

The estimates also do not reveal exactly how many participants experienced virological failure, because the endpoint denominators and counts are not reported. The definition requires 2 consecutive viral loads >50 copies/mL within 2 to 4 weeks, but the registry record does not give the detailed assessment schedule or missing-data rules. A participant’s individual course between the specified assessment times cannot be reconstructed from the reported percentages.

The design’s stated target and power assumptions are not themselves findings. The study description says it aimed to show efficacy >90%, assuming a success rate >95%, with 80% power and a 5% type-I error. The record does not report a formal test against the target or explain a decision rule, so the observed percentages alone should not be treated as a documented test result. Similarly, the safety counts are descriptive and do not permit comparative risk estimates.

In statistical terms, the registry offers a useful description of outcomes during follow-up in a specified study group, with reported uncertainty around the suppression estimates. It does not provide the design or analysis needed to attribute differences to treatment or to establish comparative conclusions. The limits are part of interpreting the result, not evidence that the observed estimates are incorrect.

13. Why This Trial Matters Statistically

This trial is statistically notable for asking a maintenance question in a population already described as virologically suppressed. The endpoint is not initial treatment response; it is the proportion meeting a defined suppression criterion after a regimen switch. That distinction affects what the estimate represents and which populations it can reasonably describe.

The registry also makes the design assumptions visible: the stated goal was efficacy >90%, with an assumed success rate >95%, 80% power, a 5% type-I error, and a required enrollment of 160 individuals. Comparing those planning statements with the reported estimates can help readers distinguish hypotheses and design targets from observed outcomes. The stated assumptions do not replace a reported analysis plan, and a planned power value is not observed power.

At the same time, the single-group structure demonstrates why a high observed proportion is not equivalent to a comparative treatment effect. A descriptive rate can characterize outcomes among participants receiving a regimen, but a treatment comparison needs an appropriate comparator and analysis. The lack of randomization and the open-label design also make the study’s inferential scope different from that of a randomized, masked comparison.

The record illustrates the importance of complete statistical reporting. Confidence intervals accompany the primary percentages, but interval methods, endpoint denominators, missing-data handling, and analysis populations are not reported. These details are necessary for readers to understand precision and the population represented by the estimates. The listed secondary outcomes further raise questions about prespecification and multiplicity that the record does not resolve.

For clinical researchers and biostatisticians, the central lesson is to align the strength of a conclusion with the design and reporting available. The suppression results are informative as descriptions of this study group, while the absence of a comparator and incomplete analysis details constrain broader or causal interpretations.

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.

Several limitations are specific to the information recorded for this study. The single-group, nonrandomized design does not provide a concurrent treatment comparator, so outcomes cannot be interpreted as a randomized estimate of the effect of switching. The open-label design is reported, while masking of outcome assessment is not described. The registry record does not report additional participant characteristics, detailed eligibility criteria, or the distribution of participants across relevant clinical subgroups, limiting assessment of how broadly the findings may apply.

The primary outcome results are presented as percentages and confidence intervals, but the record does not give the endpoint denominators or numbers meeting the success definition. It does not identify the method used to calculate the confidence intervals, describe the assessment schedule, or state how missing measurements and withdrawals were handled. These omissions limit evaluation of both the precision and the analysis population represented by the estimates.

The record lists multiple secondary outcomes but does not report a statistical analysis plan, multiplicity procedures, or a testing hierarchy for assessments at week 48 and week 96. It does not report whether the two time points were analyzed as co-primary or whether one was intended to support the other. While the study description gives design assumptions and a required sample size, detailed sample-size justification and any formal rule for evaluating the stated efficacy target are not reported in the registry record.

For safety, the record provides group counts and selected serious-event terms, but does not explain event ascertainment, attribution, follow-up duration for safety, or whether event categories overlap. It also does not provide a comparator. These reporting limits do not negate the reported observations, but they constrain how completely they can be assessed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRAL — NCT02212379.
• Registry record last updated 2026-04-03; status last verified 2021-03.
• Results first posted 2021-02-05.
• 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.

18. Record Summary

The registry record describes NCT02212379, a completed phase II study sponsored by ANRS, Emerging Infectious Diseases. It was a multicenter, international, open-label, nonrandomized, single-group trial enrolling 170 participants. The target population was virologically suppressed HIV-1-infected people aged at least 45 years switching from a boosted protease inhibitor-containing regimen to raltegravir plus etravirine.

The primary outcome was successful virological suppression at weeks 48 and 96, defined by the absence of 2 consecutive plasma viral loads >50 copies/mL within 2 to 4 weeks of the dual regimen. The record reports 99.4% success at week 48, with a 95% confidence interval of 95.6 -99.9, and 98.7% at week 96, with a 95% confidence interval of 95.0 -99.7. It also reports 165 participants at risk for safety outcomes, 26 affected by serious adverse events, 23 affected by other adverse events, and 0 deaths.

The registry describes a design target and sample-size assumptions but does not report the detailed analysis plan, endpoint denominators, missing-data procedures, or a comparative group. The results are therefore best read as descriptive outcomes for the study population.