Management of Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Antiretroviral (ARV) Combination Therapy Including Raltegravir (MK-0518-138): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Management of Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Antiretroviral (ARV) Combination Therapy Including Raltegravir (MK-0518-138) (NCT01048671), a registered phase not stated study. The primary outcome is Percentage of Participants Responding to Treatment: All Treated Participants.

2. Clinical Question

The study aimed to evaluate management of participants receiving raltegravir-containing combination therapy across France. Because treatment was chosen at the investigator’s discretion and there was no stated randomized control arm, the central statistical question is how the observed response was described, not whether it differed from a randomized alternative. The subgrouping by prior treatment experience may help characterize response in clinically different histories, but subgroup estimates and comparisons are not reported in the registry record.

3. Trial Design

This completed study evaluated management of HIV-1 participants receiving antiretroviral combination therapy including raltegravir. The registry lists enrollment of 482 and identifies France as the study setting. The recorded start is 2010-01, and the primary completion date is 2012-12. The study’s stated purpose was to evaluate treatment management in a real-life setting.

The record specifies one treatment arm: antiretroviral combination therapy including raltegravir. It says treatment was at the investigator’s discretion, with standard care in a real-life setting. Raltegravir and non-raltegravir antiretroviral drugs are listed as interventions, but the record does not specify a uniform combination regimen, dose, or treatment schedule. Those details are not reported in the registry record.

This is not a randomized comparison according to the registry information. No allocation method is stated, and there is no like-for-like control arm. The prior antiretroviral experience categories—ARV naïve, suppressed, and virological failure—are subgroups for analysis within the single treatment arm. They should not be interpreted as assigned treatment groups.

The primary endpoint was assessed 24 months after raltegravir treatment began. Its analysis population included participants with a viral-load assessment available at that time. Thus, the endpoint is based on available assessments, not necessarily on everyone enrolled. The number with an available assessment and the handling of participants without one are not reported in the registry record. The record also lists a secondary outcome concerning participants with at least one adverse event and six outcome measures, but the remaining measure details 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 482 participants included in the trial, 2 were excluded from analysis. A single treatment arm was specified in the study, but participants were sub grouped by their prior ARV experience at Baseline (ARV naïve, suppressed, or virological failure) for analysis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Two participants were excluded for protocol violation (inclusion criterion not met) and data were missing for 3 additional participants.

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 Responding to Treatment: All Treated Participants, measured over 24 months after start of raltegravir treatment.

The primary endpoint is the percentage of participants responding to treatment among all treated participants, with response defined as a viral load <50 RNA copies/mL. It was assessed 24 months after the start of raltegravir treatment. A viral-load threshold turns a continuous laboratory measurement into a binary outcome: each participant with an available assessment is classified as meeting or not meeting the stated response definition.

Such a measure is used to describe the proportion of an analysis population meeting a prespecified clinical or laboratory criterion at a particular follow-up time. It can make the result easier to interpret than a mean viral-load value alone, but it does not describe the full distribution of viral loads or the course of each participant’s measurements over time. The registry record does not state whether repeated assessments or changes from baseline were part of this endpoint.

The analysis population matters to interpretation. The registry defines it as participants with a viral-load assessment available at 24 months and notes subgroups according to prior ARV experience at baseline. The number analyzed and the response percentage are not reported in the registry record. A 95% confidence interval is identified as the endpoint’s dispersion measure, but its limits are also not reported. Consequently, the endpoint definition is clear, while its observed value and precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response summarized as a percentage. Each participant with an available viral-load assessment at 24 months can be classified relative to the threshold: viral load <50 RNA copies/mL meets the registry’s response definition. The percentage is ordinarily interpreted as the fraction of the endpoint analysis population meeting that criterion. The registry identifies a 95% confidence interval as the measure of dispersion, but neither the percentage nor interval limits are reported in the registry record.

What does a confidence interval add?

General statistical explanation: an estimate from observed participants is subject to sampling variability. A confidence interval communicates uncertainty around that estimate under a specified statistical method and its assumptions. It is not a guarantee that the true value lies within the interval, nor does it describe variation among individual participants. For a binary percentage, the interval’s precision depends in part on the number analyzed and on the observed proportion. Those endpoint details are not reported in the registry record, so the width and reliability of the interval cannot be assessed.

What does the analysis population mean?

The registry defines the primary analysis population as all participants with a viral-load assessment available at 24 months. This is an available-assessment population. It differs conceptually from an analysis that includes every enrolled participant regardless of whether the follow-up outcome was observed. The record does not report the number assessed, the number without an assessment, reasons for missing assessments, or methods such as imputation or sensitivity analysis. It also does not report whether participants who discontinued treatment could still contribute an assessment.

How should the baseline subgroups be read?

Participants were subgrouped by prior ARV experience at baseline: ARV naïve, suppressed, or virological failure. These categories describe treatment history and are not randomized assignments. Comparisons among them, if made, would be observational and could reflect differences in participant characteristics or clinical history as well as treatment response. The registry record does not report subgroup estimates, subgroup denominators, or tests comparing subgroup outcomes. No conclusion about differences between these categories can be drawn from the available registry results.

What does the design permit?

General statistical explanation: randomized allocation can help balance measured and unmeasured characteristics between treatment groups, while an uncontrolled treatment cohort cannot provide that same protection against confounding. Here, the record describes a single treatment arm with care at investigator discretion and does not state a randomized allocation. The endpoint can therefore be read as a descriptive outcome in the assessed cohort, not as a controlled estimate of a treatment effect. The registry does not report an adjusted analysis or a statistical model for the primary outcome.

What do the planning illustrations represent?

The sample-size figures are planning illustrations based on the observed effect, under the stated assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are not the trial’s own design justification and are not observed power. For non-time-to-event outcomes, such illustrations are expressed as participants per arm; time-to-event illustrations are described as total event counts. The actual illustration values and the observed effect are not reported in the registry record. Because this study is described as a single treatment arm rather than a two-arm randomized comparison, those hypothetical planning assumptions should not be mistaken for the design used in this cohort.

The registry does not report the statistical test, interval construction method, adjustment strategy, model specification, or analysis plan for the primary endpoint. General methods can explain what proportions and confidence intervals mean, but they cannot substitute for those missing details or determine how the posted endpoint was calculated.

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("ARV naïve at Baseline", "Suppressed at Baseline", "Virological Failure at Baseline")
n      <- c(52, 230, 125)
events <- c(49, 217, 89)
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  ARV naïve at Baseline  52  49  94.2  84.1  98.8  84.4  98.0  84.3  97.9
ARM  Suppressed at Baseline  230  217  94.3  90.5  97.0  90.6  96.7  90.6  96.6
ARM  Virological Failure at Baseline  125  89  71.2  62.4  78.9  62.7  78.4  62.7  78.4

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is defined as response at 24 months, while the registry also lists a secondary outcome concerning participants with at least one adverse event and six outcome measures in total. The other measure descriptions and results are not reported in the registry record. With multiple outcomes or subgroup analyses, multiplicity can arise when many statistical questions are tested: the chance of at least one apparently notable result can increase if no adjustment or prespecified hierarchy is used. The record does not report a multiplicity strategy, endpoint hierarchy, or which outcomes were formally tested.

The registry lists zero analysis records. This does not establish that no analyses were conducted; it means that analyses are not listed in the registry record. No primary-endpoint test statistic, p-value, adjusted estimate, or model result is reported. The endpoint names a 95% confidence interval, but the interval itself is absent.

Missing endpoint data are important because the primary population was defined by availability of a 24-month viral-load assessment. The count with an assessment, the count without one, reasons for missingness, and any method used to address missing data are not reported in the registry record. The record does not state whether the analysis used only observed assessments, carried values forward, imputed outcomes, or performed sensitivity analyses; none of these approaches should be assumed.

The distinction between the enrollment figure and the primary analysis population is therefore essential. Enrollment describes the study cohort, whereas the response endpoint was limited to participants with an available assessment at the specified time. The registry does not report enough information to determine how representative that assessed group was of all enrolled participants or how missing outcomes could affect the response estimate.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: depression (1.0%), suicide attempt (0.8%), headache (0.6%), asthenia (0.4%), general physical health deterioration (0.4%).

For the antiretroviral combination therapy group including raltegravir, the registry reports 480 participants at risk for serious adverse events and 66 affected participants. For other adverse events, it reports 480 at risk and 27 affected participants. These are separate registry categories; the counts should not be added to infer a total number of people with any event, because participants may appear in more than one category. The registry does not report deaths in this group.

The listed serious adverse event terms and percentages are depression, 1.0%; suicide attempt, 0.8%; headache, 0.6%; asthenia, 0.4%; general physical health deterioration, 0.4%; and Pneumocystis jiroveci pneumonia, 0.4%. These are the terms identified in the registry’s leading serious-event list, not a complete description of every event or a comparative risk estimate.

General statistical interpretation: an affected-participant count describes how many people were recorded in the category, while the risk-set count indicates the number reported as at risk. Such counts do not establish causation. The registry record does not describe event onset, duration, severity grading beyond the serious-event classification, exposure time, adjudication, or a control-group rate. The figures therefore characterize reported safety events in the treatment group but cannot determine whether treatment caused them or how they compare with another treatment.

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

The record establishes the study question, the response definition, and the follow-up time: participants with an available assessment were classified according to whether their viral load was <50 RNA copies/mL at 24 months after starting raltegravir. It also documents a French real-life treatment setting, investigator discretion, a single treatment arm, and subgrouping by prior ARV experience.

However, the main numerical result needed to judge the endpoint is not reported in the registry record. The response percentage, its confidence interval, and the endpoint analysis denominator are absent. As a result, the posted results do not establish the observed response level or how precisely it was estimated. Enrollment of 482 cannot be used as the primary endpoint denominator because the analysis population required an available 24-month viral-load assessment.

The design also means that the response proportion should not be interpreted as a causal estimate of raltegravir’s effect. Participants received combination therapy, treatment was at the investigator’s discretion, and no randomized comparison arm is specified. Outcomes could reflect the overall treatment regimen, prior ARV experience, participant characteristics, and routine-care decisions. The registry record does not report an adjusted comparison that would address these factors.

The safety figures document affected participants in the reported categories and list selected serious-event terms. They do not show that treatment caused the events, and there is no comparator rate in the record for judging relative safety. Deaths are not reported in the registry record.

General statistical point: descriptive outcome data can be informative about what was recorded in a cohort, but conclusions depend on the completeness of follow-up, the analysis population, and the precision of estimates. Here, missing assessment details and absent endpoint estimates prevent a full evaluation. The findings should therefore be read as a registry description of a treatment-management study, not as proof of comparative benefit or harm.

14. Why This Trial Matters Statistically

This study is statistically notable because its central question concerns outcomes in a real-life treatment setting rather than a stated randomized comparison. Such data can describe how a treatment strategy was managed in routine care and what outcomes were recorded among participants assessed at follow-up. The registry identifies the clinical response threshold and follow-up time, making the intended endpoint interpretable even though its observed value is not reported.

The population definition highlights a recurring issue in longitudinal clinical research: the group with an available follow-up measure may differ from the group originally enrolled. The endpoint included participants with a 24-month viral-load assessment, but the registry does not report how many had one or why assessments were unavailable. Without those details, the endpoint denominator and the potential influence of missing follow-up cannot be evaluated.

The study also illustrates why a single-arm proportion and a comparative treatment effect are different statistical quantities. A response percentage can describe the assessed cohort. A causal comparison requires a suitable contrast and careful handling of differences between treatment groups. The record specifies one treatment arm, investigator discretion, and baseline subgroups; it does not specify randomized allocation or a control group. Subgroup labels should therefore be read as descriptive categories, not as evidence of treatment contrasts.

Finally, naming a confidence interval does not itself convey precision. The actual endpoint estimate and interval limits are necessary for readers to assess uncertainty. Their absence, alongside unreported analysis details, limits statistical interpretation. The record remains useful for understanding the study’s intended endpoint, care context, and reported safety counts, while leaving the magnitude and precision of the primary result unresolved.

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 primary response result and its 95% confidence interval are not reported in the registry record. Nor is the number of participants included in that endpoint analysis. Although enrollment is recorded as 482, the primary endpoint was restricted to participants with an available viral-load assessment at 24 months, so the size of the analyzed population cannot be inferred from enrollment.

Follow-up completeness and missing-data handling are not reported in the registry record. There are no reported counts or reasons for unavailable assessments, and no stated method for handling them. The record also does not describe how the confidence interval was calculated, whether analyses were adjusted, or whether sensitivity analyses were performed.

The design is a single treatment arm with treatment at investigator discretion in a real-life setting. No randomized control group or allocation method is stated. This limits causal and comparative interpretation, particularly because participants received combination therapy and could differ in prior ARV experience. The record does not report subgroup response estimates or analyses that address potential confounding.

The registry lists six outcome measures, but details for all measures are not present. It does not report a multiplicity plan or a statistical analysis plan. Safety information includes reported risk sets, affected counts, and selected serious-event terms, but deaths are not reported in the registry record, and event timing, exposure duration, and causal assessment are not described. These limitations mean the record supports a description of the intended study and the safety counts, but not a complete assessment of endpoint magnitude, precision, or comparative effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Management of Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Antiretroviral (ARV) Combination Therapy Including Raltegravir (MK-0518-138) — NCT01048671.
• Registry record last updated 2015-10-30; status last verified 2015-10.
• Results first posted 2014-02-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed study of management of HIV-1 participants treated with antiretroviral combination therapy including raltegravir in France. Enrollment was 482; the recorded study start was 2010-01 and primary completion was 2012-12. Treatment was at investigator discretion in a real-life setting, with one specified treatment arm and baseline subgrouping by prior ARV experience.

The primary endpoint was the percentage with viral load <50 RNA copies/mL at 24 months among participants with an available assessment. The response percentage, confidence interval limits, and analysis denominator are not reported in the registry record. Safety figures list 66 of 480 at risk for serious adverse events and 27 of 480 at risk for other adverse events; deaths are not reported in the registry record. The record does not specify a randomized comparison, and it does not provide enough endpoint or analysis detail for a comparative or causal interpretation.