Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients (NCT01605890), a na phase 2 study. The primary outcome is Percentage of Participants in Therapeutic Success.

2. Clinical Question

The clinical rationale in the record is that treatment strategies used for HIV-1 may not perform as well for HIV-2, and that options for later-line treatment are limited. The investigators described the trial as an initial phase 2 evaluation of a regimen combining two NRTIs with raltegravir. The stated hypothesis was that the regimen would achieve therapeutic success of at least 50% at Week 48. That figure is a hypothesis in the study description, not an observed result.

The primary question is consequently about the frequency of a prespecified composite outcome in the treated group, rather than whether the regimen outperforms another treatment. Without a concurrent comparator, the observed outcome cannot establish a comparative treatment effect. Results for the primary outcome, including the number of participants meeting the success definition, are not reported in the registry record.

3. Trial Design

The registry identifies NCT01605890 as a phase 2 study titled “Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients.” Its official title is “ANRS 159 VIH-2 : Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients.” ANRS, Emerging Infectious Diseases is listed as the sponsor. The condition is HIV-2 infection.

The design is recorded as single-group, with allocation not applicable and masking none. The intervention is emtricitabine, tenofovir disoproxil fumarate and raltegravir. No separate control group is listed, so the design does not support a randomized comparison between regimens. The registry reports an enrollment of 30. It records a start in 2012-07, primary completion in 2015-12 and status as completed.

The study description presents the regimen as a first-line strategy and an alternative to classical triple therapy. Its stated purpose was to assess whether a strategy involving two NRTIs and raltegravir produced an immunovirological response at least as good as that obtained with triple therapy. However, the registered design does not include a concurrent triple-therapy group. The background comparison therefore describes the rationale, not a comparison made within this trial.

Further design details—including eligibility criteria, recruitment procedures, follow-up completeness, the planned analysis population and the statistical plan—are not reported in the registry record. The record identifies 12 outcome measures and lists secondary outcomes involving CD4 lymphocyte changes, clinical and biological events, HIV-2 RNA, adherence, resistance mutations, and treatment switch or discontinuation. Results for those outcomes are not reported in the registry record.

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 the 38 participants screened between July 2012 and January 2015, 30 (78.9%) participants were finally included.

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 Percentage of Participants in Therapeutic Success, measured over at Week 48.

The primary endpoint is the percentage of participants in therapeutic success at Week 48. It is a composite endpoint: a participant is considered not to have achieved success if any listed failure condition occurs. Those conditions are HIV-2 RNA at or above 100 copies/mL beginning at Week 24 and confirmed within the next four weeks; a CD4 lymphocyte gain below 100/mm3 at Week 48 relative to the average counts between Week-4 and Week 0; permanent raltegravir discontinuation; death from any cause; or a new B or C event confirmed by an endpoint review committee.

A composite can capture several ways a treatment strategy might fail, including virological, immunological, treatment-related and clinical events. It can therefore represent a broader treatment outcome than any single component. At the same time, the overall percentage combines distinct event types, and a single composite result would not by itself show which component contributed most. Component-specific results are not reported in the registry record.

The Week 48 time point and the stated event criteria define the outcome being assessed; the result would be interpreted as the proportion meeting this particular definition, not as a general measure of every aspect of HIV-2 treatment. The registry lists a 95% confidence interval as the dispersion measure, but does not report the primary endpoint estimate or its interval. The rationale for choosing this composite and further details of endpoint adjudication beyond confirmation of new B or C events are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

The primary outcome is expressed as a percentage of participants meeting a binary definition: each participant either meets the therapeutic-success criteria or does not. The criteria combine several clinical and laboratory events. This kind of endpoint is often called a composite because its classification depends on whether any of the specified components occurs. The record gives the component definitions, but does not report component-specific results or explain how each component was expected to contribute to the overall outcome.

For a binary outcome, a percentage describes the observed frequency of the defined event in the population analyzed. The estimate is tied to the endpoint definition, the follow-up time and the analysis population. It does not automatically describe outcomes beyond Week 48 or outcomes measured using a different definition. The registry does not report the primary estimate or the analysis population used, so neither can be interpreted from this record.

What does a confidence interval communicate?

The registry specifies a 95% confidence interval for the primary percentage. In general, a confidence interval communicates statistical uncertainty around an estimate: it gives a range of values compatible with the observed data under the chosen method and its assumptions. It is not a guarantee that the true value lies in that particular interval, nor does it resolve limitations in the design or measurement.

The width of an interval is informative about precision. Less information in the data generally leads to less precise estimates, while more information can yield greater precision, subject to the analysis and outcome. The registry record does not report the interval’s endpoints, so its width and the precision of the primary estimate cannot be assessed.

What can a single-group design estimate?

A single-group study can describe outcomes observed among participants receiving the study intervention. It cannot provide the same direct estimate of a treatment contrast as a trial with a concurrent randomized comparator. In a non-comparative design, changes or events may reflect the treatment, participant characteristics, the natural course of illness, other care or measurement processes. Without a control group, those influences cannot be separated through a randomized between-group comparison.

The record identifies no masking and records allocation as not applicable. These design features do not negate the descriptive value of observed outcomes, but they matter when considering potential sources of bias. The registry does not report further details about outcome assessment procedures, adherence to the intervention or handling of departures from treatment.

What do the planning illustrations represent?

The registry’s planning assumptions describe illustrations based on the observed effect, rather than the trial’s own design justification. They specify a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations: they show how a hypothetical future design might be sized under assumptions. They are not evidence that the present single-group trial had those design features, and they are not observed power.

Observed power is not a substitute for an effect estimate and its uncertainty. For interpreting a completed study, the estimate and its confidence interval are more directly informative. The record does not report a sample-size justification for this trial, and the planning assumptions should not be attributed to the trial’s original protocol.

Why do outcome definitions and event rates matter?

Composite endpoints make multiple event types part of one outcome. This can be useful when a trial aims to capture a broad clinical response, but interpretation depends on knowing which components occurred and how frequently. Components may differ in clinical importance and frequency. A composite percentage alone can conceal that variation, so component-level reporting helps explain what the result represents. Such component results are not reported in the registry record.

For outcomes based on event counts, general statistical methods may need to account for variation in event rates and for over-dispersion, which occurs when observed variation exceeds what a simpler model assumes. This is a general consideration, not a statement about the analysis used in this trial. The registry record does not report an analysis method for event counts or whether over-dispersion was assessed.

More generally, statistical interpretation depends on prespecified definitions, consistent follow-up, appropriate handling of missing observations and a clearly described analysis population. These details are not reported in the registry record. No statistical analysis is listed in the registry, so a reader cannot assess the methods used to estimate the primary outcome or to address these issues.

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("Raltegravir / Emtricitabine / Tenofovir Disoproxil")
n      <- c(30)
events <- c(12)
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  Raltegravir / Emtricitabine / Tenofovir Disoproxil  30  12  40.0  22.7  59.4  24.6  57.7  24.5  57.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary therapeutic-success outcome and secondary measures concerning immune response, virological status, clinical and biological events, adherence, resistance and treatment changes. When a study evaluates multiple outcomes, the chance of apparently notable results arising by chance can increase if many tests are conducted. Statistical approaches can address this issue, or investigators may distinguish a primary outcome from secondary and exploratory outcomes. The registry record does not report a multiplicity strategy, whether secondary outcomes were adjusted, or which analyses were treated as confirmatory.

The registry lists no statistical analyses. This means the record does not describe how outcome estimates were produced, what inferential tests were used, or whether analyses followed a prespecified plan. It does not establish whether analyses were or were not performed outside the registry record. The statistical analysis plan, including any interim analyses, is not reported in the registry record.

Missing data can affect both the estimated percentage and its precision, particularly if missingness is related to outcomes or treatment discontinuation. General approaches include defining an analysis population, describing missingness and conducting sensitivity analyses under different assumptions. The record does not report the amount or handling of missing outcome data, the analysis population, or sensitivity analyses. It also does not report how participants with incomplete follow-up were treated in the primary endpoint analysis.

These omissions prevent assessment of whether the reported analysis, if available elsewhere, would address multiplicity and missingness in a way consistent with the trial’s objectives. The primary result itself is not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lacunar ischemic stroke (3.3%), helicobacter pylori gastritis, escherichia coli cystitis (3.3%), suspected recurrence of bronchopulmonary cancer (3.3%), truvada overdose without any adverse event (3.3%).

For the raltegravir, emtricitabine and tenofovir disoproxil fumarate group, the registry lists 30 participants at risk for serious adverse events and a serious-event figure of 4. It lists 30 participants at risk for other adverse events and an other-event figure of 14. The record reports 0 deaths. These are descriptive safety counts; without a comparator group, they do not estimate a difference in risk between treatments.

The registry names lacunar ischemic stroke at 3.3%; Helicobacter pylori gastritis and Escherichia coli cystitis at 3.3%; suspected recurrence of bronchopulmonary cancer at 3.3%; and Truvada overdose without any adverse event at 3.3% among the top serious terms. The second listing combines two event descriptions, and the overdose listing explicitly notes no adverse event. The term list should therefore be read as registry coding and reporting, not as a set of equivalent clinical outcomes.

The record does not provide further detail about event severity, timing, relatedness to treatment, recurrence, or how serious events were defined and adjudicated. The listed counts and terms alone cannot establish causality, compare safety with another regimen or characterize the full safety profile. Further safety results are not reported in the registry record.

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

The registry record establishes that a phase 2, single-group study evaluated a first-line combination of raltegravir, emtricitabine and tenofovir disoproxil fumarate in HIV-2 infection. It specifies a Week 48 composite definition of therapeutic success and records an enrollment of 30. Those details clarify what the trial set out to assess.

The record does not report the primary outcome estimate, its 95% confidence interval or the component results. It therefore does not show how many participants met the definition, how precisely the percentage was estimated, or which types of event shaped the outcome. The stated success threshold of at least 50% is a hypothesis, not a reported finding.

The design also sets limits on what the trial can establish. Because no concurrent control group is listed, the study cannot directly estimate the difference between this regimen and classical triple therapy or another strategy. The trial description discusses that comparison as a clinical rationale, but it is not a randomized comparison within the registered design. Nor can a single-group outcome, on its own, distinguish treatment effects from other influences on participants’ outcomes.

The safety record gives descriptive event figures and several serious-event terms, but does not provide a comparative safety analysis or detailed information on event attribution. Secondary outcome results and analysis details are also not reported in the registry record. Accordingly, the available record supports an understanding of the study question, intervention and endpoint definition, but not a conclusion about the observed efficacy or comparative safety of the regimen.

14. Why This Trial Matters Statistically

This trial illustrates the importance of separating a study’s rationale from its design and results. The background describes a need to evaluate treatment strategies for HIV-2 and presents an alternative regimen as a candidate for first-line use. The registered study, however, is single-group. Its structure can describe outcomes in the treated group but cannot supply the randomized contrast implied by comparisons with classical triple therapy.

Its composite primary endpoint also highlights a central interpretive issue: an overall success percentage can combine virological, immunological, treatment-discontinuation, mortality and clinical-progression criteria. That breadth may capture several dimensions of response, but meaningful interpretation depends on the overall estimate, its uncertainty and the outcomes contributing to it. The registry record gives the endpoint rules but not the result or component breakdown.

The record also demonstrates why completeness of statistical reporting matters. A confidence interval is specified, yet its values are not reported; outcome measures are listed, but their results are not; and the statistical analysis is not described. Without those details, readers cannot assess the primary estimate’s precision, the handling of missing data or the treatment of multiple outcomes.

For biostatistical interpretation, the key distinction is between evidence that a question was posed and evidence that answers it. A prespecified endpoint and a stated hypothesis define the intended assessment, but they do not establish an outcome. Clear reporting of estimates, uncertainty, analysis populations and component results is necessary to evaluate what the data support.

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 most immediate limitation of the registry record is that it does not report the primary therapeutic-success result or its confidence interval. It also does not report results for the listed secondary outcomes. The study’s clinical outcome therefore cannot be evaluated from the posted registry results.

The single-group design has no listed concurrent comparator, so it cannot support a randomized estimate of the difference between this regimen and another treatment strategy. The lack of masking is recorded, but further information about outcome assessment and safeguards against bias is not reported in the registry record. This is particularly relevant to components involving clinical events, discontinuation and committee confirmation.

Further details needed to assess the trial’s conduct and analysis are not reported in the registry record. These include eligibility criteria, participant flow, follow-up completeness, the analysis population, missing-data handling, the statistical analysis plan, multiplicity procedures and any interim analyses. A sample-size justification for the trial is not reported. The planning assumptions described in the record are illustrations based on an observed effect, not the trial’s own design justification.

The safety information is also limited: the record provides event figures and selected serious-event terms but not detailed timing, treatment relatedness, adjudication or comparative safety results. Finally, the registry description’s intended comparison with classical triple therapy should not be mistaken for a comparison performed by this single-group study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients — NCT01605890.
• Registry record last updated 2026-04-02; status last verified 2026-04.
• Results first posted 2018-07-20.
• 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

NCT01605890 is a completed phase 2, single-group trial sponsored by ANRS, Emerging Infectious Diseases. It evaluated raltegravir, emtricitabine and tenofovir disoproxil fumarate as a first-line combination in HIV-2 infection. The registry records enrollment of 30, a start in 2012-07 and primary completion in 2015-12. Allocation is listed as not applicable and masking as none.

The primary endpoint was the percentage of participants in therapeutic success at Week 48, based on specified virological, immunological, discontinuation, mortality and clinical-event criteria. The registry lists a 95% confidence interval as the dispersion measure. It does not report the primary estimate, its interval or results for the listed secondary outcomes. No statistical analyses are listed.

The registry reports serious-event and other-event figures for the intervention group and records 0 deaths. The design does not include a concurrent comparator, so it does not provide a randomized treatment comparison. The main statistical conclusion is that the record describes the question and endpoint but does not report the results needed to assess the outcome.