A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen. (NCT01328041), a na phase 3 study. The primary outcome is Mean Change From Baseline in Plasma HIV-1 RNA at Day 8.

2. Clinical Question

The trial focused on a short-term laboratory measure in a population with prior treatment failure on an integrase inhibitor-containing regimen. Its primary endpoint asks about the average within-participant change over the period from baseline to Day 8, rather than a difference between treatment groups. The trial also listed outcomes covering later HIV-1 RNA measurements, CD4+ and CD8+ cell counts, disease progression, and dolutegravir concentrations. Those outcomes broaden the planned assessment, but they do not turn the single-group study into a comparative trial. Without a reported primary estimate and a concurrent control group, the registry record cannot establish how the measured change compares with what would have occurred under another treatment strategy.

3. Trial Design

This was a Phase III, single-group study sponsored by ViiV Healthcare. The registry lists 183 participants enrolled, the study status as completed, and no masking. Allocation is listed as not applicable. The study concerned HIV-1-infected adults with antiretroviral treatment experience and current or historical treatment failure on a regimen containing an integrase inhibitor.

Participants received dolutegravir 50 mg twice daily. The brief summary describes starting dolutegravir alongside the current failing antiretroviral therapy regimen and moving to an optimized background regimen after Day 7. The arm description characterizes the regimen as dolutegravir plus background antiretroviral therapy optimized at Day 8. These descriptions indicate a change in the background regimen during the early study period; the registry record does not describe a separate control arm.

The primary endpoint was mean change in plasma HIV-1 RNA from baseline to Day 8. The registry says the first analyses would be conducted after the last participant enrolled had completed 24 weeks, and that participants could remain in the study after Week 24. Study start and primary completion are listed as 2011-05 and 2012-05. Those dates describe the registry record and do not supply the missing numerical primary result.

The design can describe outcomes observed during treatment in this enrolled group. Because it is single-group and unmasked, it cannot provide a randomized contrast with an alternative regimen, and changes over time cannot be attributed solely to dolutegravir on the basis of this design. The statistical analysis plan, sample-size justification, and details of any interim analyses 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: A total of 139 par. were screen failures and 183 par. entered the single arm, open-label study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat-Exposed (ITT-E) Population: all participants who received at least one dose of study drug. Only participants who had Day 8 observations were considered for analysis.

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 Mean Change From Baseline in Plasma HIV-1 RNA at Day 8, measured over Baseline and Day 8.

The primary endpoint is mean change from baseline in plasma HIV-1 RNA at Day 8, measured in log10 copies/milliliter. The change is defined as the Day 8 measurement minus the baseline measurement. It is a continuous outcome, so the reported mean would describe the average change among the participants included in this endpoint analysis. The registry record does not report the mean change, its standard deviation, or an uncertainty interval.

HIV-1 RNA is a laboratory measure of the amount of viral RNA in plasma. In general, a change score expresses how a measurement differs from its starting value, while using the same participants’ baseline and follow-up values can account for some of the variation in their starting measurements. The mean is useful for describing the central tendency of a continuous outcome, but it does not show how widely individual participants’ changes varied. That is why a dispersion measure, such as the standard deviation listed for this endpoint, is also informative.

The endpoint is short-term: it compares baseline with Day 8, rather than describing the later follow-up outcomes listed elsewhere in the registry. The analysis population was restricted to participants with a Day 8 observation, although the endpoint description also specifies rules for carrying observations forward when Day 8 was missed or treatment discontinued before then. The record does not reconcile those statements in further detail.

As a single-group endpoint, the mean change describes the observed course in the analyzed participants. It is not a between-group treatment effect. Without a concurrent comparator, the change alone cannot separate the contribution of study treatment from other influences on measurements over time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary endpoint is a continuous measurement summarized as a mean change. Each change is formed by subtracting the baseline value from the Day 8 value, and the endpoint is the average of those changes in the analysis population. This gives a compact description of the group’s average movement over time. It does not imply that every participant had the same change, nor does it describe the full spread of individual outcomes. The registry identifies the standard deviation as the dispersion measure, but does not report its value.

In general, the standard deviation describes how spread out observations are around their mean. It is distinct from the standard error, which describes the uncertainty of an estimated mean. A mean and standard deviation together can help describe the distribution, while a confidence interval for the mean would express uncertainty in the estimated average. The numerical endpoint result and uncertainty measures are not reported in the registry record, so those features cannot be evaluated for this study.

Why express the endpoint as a change?

A change score puts the follow-up measurement in relation to each participant’s starting measurement. In general, this can make the result easier to interpret as movement from baseline and can account for differences in starting levels when summarizing within-person change. It still leaves important questions: how much participants varied, whether the average is sensitive to unusual observations, and whether changes can be linked to the intervention rather than other events during follow-up. The registry’s single-group design does not resolve the last question through a concurrent randomized comparison.

What does the analysis population mean?

The endpoint description defines the Intent-to-Treat-Exposed population as participants who received at least one dose of study drug, and states that only participants with Day 8 observations were considered for the primary analysis. This definition combines exposure to study drug with availability of a follow-up measurement. In general, restricting an analysis to participants with observed follow-up can affect the interpretation if missingness is related to outcome or participant characteristics. The registry does not report the number of participants included in the primary endpoint analysis or provide a comparison of those with and without Day 8 observations.

The endpoint description also states that the last observation was carried forward if a participant missed the Day 8 visit, and that baseline was carried forward if a participant discontinued treatment before Day 8. These rules are forms of imputation: a recorded value is used in place of an unobserved follow-up value. In general, carrying a prior value forward assumes that the carried value is a reasonable stand-in for the missing measurement. That assumption may not reflect the participant’s actual later value, particularly when the outcome can change over time. The record does not explain how these rules relate to the statement that only participants with Day 8 observations were analyzed, nor does it report sensitivity analyses using alternative missing-data assumptions.

How should a within-group result be read?

In a single-group study, the primary mean change describes the group’s observed baseline-to-follow-up movement. It is not an estimate of the difference between two assigned treatments. General statistical reasoning distinguishes a change occurring during treatment from a causal effect attributable to treatment: without a comparison group, other changes over time may also contribute to the observed result. Here, the background antiretroviral therapy regimen was optimized during the early study period, so the treatment context was not dolutegravir alone.

The lack of masking is also part of the design record. In general, masking can reduce certain forms of influence on treatment delivery, outcome assessment, or reporting, depending on the outcome and trial procedures. The registry identifies no masking, but does not give enough detail to determine how outcome measurement or other study procedures might have been affected. Plasma HIV-1 RNA is a laboratory measure, but no additional details about laboratory blinding or assessment procedures are reported.

What can be inferred from listed analyses?

The registry lists 19 outcome measures and 3 analyses. The presence of multiple outcomes and analyses raises a general issue of multiplicity: when many statistical questions are examined, the chance of at least one apparently notable result can increase unless the analysis approach accounts for that process. Whether an adjustment was used, which analyses were primary or secondary in the statistical plan, and how any results were selected for reporting are not reported in the registry record. No p-value for the primary endpoint is reported, so there is no basis in this record to describe statistical significance.

The registry states that first analyses would be conducted after the last participant enrolled had completed 24 weeks. That timing statement does not, by itself, describe an interim analysis plan or any monitoring procedure. Details such as prespecified analysis timing beyond that statement, stopping rules, or adjustment for repeated looks at accumulating data are not reported in the registry record.

What are planning illustrations?

Any sample-size illustration associated with these results should be read as planning information rather than an observed trial finding. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. Those assumptions do not describe the actual single-group study design, which has no separate randomized comparison arm. The registry record does not report the trial’s own sample-size justification. Planning estimates are not observed power and do not establish that a completed study had adequate precision.

More generally, statistical methods can clarify what an estimate represents, the uncertainty around it, and the assumptions needed for interpretation. For this study, key numerical outcome statistics and fuller analysis details are absent from the registry record. Interpretation should therefore stay with the documented endpoint definition, population, missing-data rules, and design, without implying a quantitative result that is not reported.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Dolutegravir 50 mg BID")
n   <- c(182)
m   <- c(-1.432)
sp  <- c(0.607)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Dolutegravir 50 mg BID  182  -1.432  0.607  -1.521  -1.343

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and 3 analyses. It describes several types of outcomes, including plasma HIV-1 RNA at multiple visits, CD4+ and CD8+ cell counts, HIV-1 disease progression, and dolutegravir concentration measures. Considering multiple outcomes or analyses creates a general multiplicity issue: the more statistical questions examined, the more important it is to know which were prespecified and whether any adjustment was planned. The statistical analysis plan and any multiplicity procedure are not reported in the registry record.

The record states that the first analyses would be conducted after the last participant enrolled had completed 24 weeks. It does not report whether this was an interim analysis, whether further formal analyses were planned, or whether any monitoring or stopping rules were used. Those details should not be inferred from the timing statement alone.

For the primary endpoint, the record specifies last observation carried forward for a missed Day 8 visit and baseline carried forward if treatment was discontinued before Day 8. It also states that only participants with Day 8 observations were considered for analysis. The relationship between these statements is not clarified. The number included in the primary endpoint analysis, the amount of missing outcome data, reasons for missingness, and sensitivity analyses are not reported in the registry record.

In general, missing-data assumptions matter because an imputed value is not the same as an observed follow-up measurement. The described carry-forward rules may affect a mean change depending on the missingness pattern and on how participant outcomes would otherwise have changed. Without outcome-level missingness information and alternative analyses, the robustness of the primary result to those assumptions cannot be assessed.

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: pneumonia (2.7%), pyrexia (1.6%), dehydration (1.6%), progressive multifocal leukoencephalopathy (1.1%), cholelithiasis (1.1%).

The registry reports that 183 participants were at risk for serious adverse events and that 46 were affected. For other adverse events, 183 were at risk and 143 were affected. These are counts recorded for the dolutegravir 50 mg BID group. The record does not report a death count.

The listed serious adverse event terms and percentages are pneumonia, 2.7%; pyrexia, 1.6%; dehydration, 1.6%; progressive multifocal leukoencephalopathy, 1.1%; cholelithiasis, 1.1%; and squamous cell carcinoma, 1.1%. These are the terms and percentages identified in the registry record; no term-specific counts are given in the information recorded.

In general, a serious adverse event is a safety category distinct from the broader category of adverse events. The group-level affected counts do not mean that every listed term occurred in every affected participant, and the term percentages should not be interpreted as treatment-attributable risks without further information. The registry record does not report a control group for comparison, nor does it establish from these figures whether an event was caused by study treatment. The reported counts and terms describe safety information recorded during this single-group study, not a comparative estimate of excess risk.

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

This record establishes the study’s question, design, and primary endpoint definition. It describes a Phase III, single-group study of dolutegravir in adults with HIV-1 and current or historical treatment failure on an integrase inhibitor-containing regimen. The primary endpoint was mean change in plasma HIV-1 RNA from baseline to Day 8, with a stated approach to missed Day 8 measurements and treatment discontinuation.

The numerical primary outcome is not reported in the registry record. Without the mean change and its dispersion or uncertainty, the direction and size of the observed result cannot be described, and its precision cannot be assessed. The record therefore does not support a quantitative statement about the primary endpoint. It also does not report a p-value or confidence interval for that result.

The single-group design is important to what the study can establish. A within-group change can describe what was observed during the study, but it is not a randomized comparison with another regimen. The background antiretroviral therapy was optimized during the early study period, so the treatment context included more than dolutegravir alone. General causal interpretation requires considering alternative explanations for change over time; this design does not provide a concurrent control group to address them.

The record lists safety counts and several serious adverse event terms, but those figures likewise do not compare treatment groups or establish causation. Other outcomes were listed, including later viral RNA and cell-count measures, disease progression, and drug concentration measures; their numerical results are not reported in the information available for this account.

Accordingly, the defensible interpretation is limited to the study’s documented purpose, regimen, endpoint, analysis population, and safety entries. It does not establish a treatment effect relative to an alternative, provide the missing primary estimate, or demonstrate what would have happened under another regimen.

14. Why This Trial Matters Statistically

The trial is statistically notable for asking a short-term laboratory question in a population described as having current or historical treatment failure on an integrase inhibitor-containing regimen. The endpoint is explicitly defined as a within-participant change from baseline to Day 8, which makes the target quantity clear. The registry also identifies the continuous-outcome summary as a mean and names the standard deviation as its dispersion measure.

At the same time, the design makes the interpretation of change especially important. A single-group study can characterize an observed trajectory but cannot provide a randomized contrast with an alternative regimen. The background regimen was optimized during the early study period, so the observed treatment setting changed around the primary endpoint. These features do not erase the value of documenting outcomes, but they constrain causal conclusions.

The missing numerical primary result is a central statistical limitation. An endpoint definition alone cannot show the size, direction, or precision of an effect. The record also lists multiple outcomes and analyses without reporting a multiplicity approach or a statistical analysis plan. Missing-data handling is described, but the record does not clarify its relation to the stated analysis population or give sensitivity analyses.

These points illustrate why statistical interpretation depends on more than naming an endpoint. Readers need the estimate, variability or uncertainty, analysis population, missing-data handling, and design context to understand what a result can support. The registry record contributes several of these definitions, but does not report the primary numerical outcome or enough analysis detail for a complete assessment.

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 direct limitation of the registry information is that it does not report the numerical primary endpoint result. The mean change in plasma HIV-1 RNA, its standard deviation, and any confidence interval or p-value are not reported in the registry record. This prevents assessment of the magnitude, direction, and precision of the primary outcome.

The study was single-group, with allocation listed as not applicable and no masking. No concurrent comparator is described, so the design cannot estimate a randomized difference between dolutegravir and another regimen. The background antiretroviral therapy was optimized during the early study period, which further means that the treatment context included a change beyond initiation of dolutegravir.

The endpoint population and missing-data description leave questions. The primary analysis considered participants with Day 8 observations, while the endpoint description also specifies carry-forward rules for a missed visit or treatment discontinuation before Day 8. The record does not clarify how those statements were applied together. The primary analysis count, extent and reasons for missingness, and sensitivity analyses are not reported.

The registry lists multiple outcomes and analyses but does not report the statistical analysis plan, multiplicity procedures, or sample-size justification. It also does not report enough detail to judge the effects of the unmasked design on study procedures. Safety information lacks a concurrent control group, and a death count is not reported in the registry record. These limitations restrict both causal interpretation and assessment of the completeness and robustness of the reported analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen. — NCT01328041.
• Registry record last updated 2016-01-07; status last verified 2015-12.
• Results first posted 2014-07-21.
• 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

NCT01328041 is a completed Phase III, single-group study sponsored by ViiV Healthcare. It enrolled 183 adults with HIV-1 infection and current or historical treatment failure on an integrase inhibitor-containing regimen. Participants received dolutegravir 50 mg twice daily with background antiretroviral therapy that was optimized after Day 7, as described in the brief summary.

The primary endpoint was mean change in plasma HIV-1 RNA from baseline to Day 8, measured in log10 copies/milliliter. The registry defines the analysis population and describes carry-forward rules for missing Day 8 measurements or discontinuation before Day 8, but does not report the numerical primary result. The design had no separate comparator arm and no masking.

The record lists 19 outcome measures and 3 analyses, along with group-level adverse event counts and serious adverse event terms. A statistical analysis plan, sample-size justification, multiplicity approach, and primary endpoint estimate are not reported in the registry record.