FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir (NCT01777997), a na phase 4 study. The primary outcome is Change in Levels of CD8+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) From Baseline to Weeks 24 and 48 on ART.

2. Clinical Question

3. Trial Design

This was a prospective, single-arm, open-label Phase 4 study of FTC/RPV/TDF in treatment-naïve HIV-1 controllers. The registry lists an enrollment of 38 and a completed status. The recorded study start was 2013-04-25, and primary completion was 2016-02-19. Because there was one treatment group and no randomized comparator, the design describes changes over time among participants receiving ART rather than a treatment contrast between groups.

Open-label means the study was not masked. The registry lists masking as none and allocation as not applicable. The intervention was a single tablet combining emtricitabine, rilpivirine, and tenofovir disoproxil fumarate. The study’s stated aims included evaluating immune activation and other biological measures, as well as safety and how participants responded to the medication.

The primary outcome was change in CD8+ T-cell activation from baseline to weeks 24 and 48 on ART. Its description says baseline included pre-ART study entry and week 0 on ART, identified as study week 12. The mean change was estimated jointly for the two follow-up times using repeated-measures analysis with generalized estimating equations. The primary outcome population was as-treated and required suppressed HIV-1 RNA, qualifying timing before the assessment, and no prohibited or precautionary medications based on team review.

The registry lists nine outcome measures, including plasma HIV-1 RNA measured by a single-copy assay, CD4+ T-cell count, CD4+ and CD8+ T-cell activation, inflammatory biomarkers, quality of life, and safety events. The registry record does not report a detailed rationale for the enrollment target, a separate control group, or a full statistical analysis plan.

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.

12 Week lead-in of no ART

Reasons for not completing this period:

Weeks 0 to 24/48 on ART

Reasons for not completing this period:

Weeks 48 to 72/96 on ART

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA \<200 copies/mL for at least 2 weeks (14 days) prior to week 24 or 48 weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

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.

Population: Participants who were on intervention (ART) for at least 24 weeks

6. Primary Endpoint

The registry lists the primary outcome as Change in Levels of CD8+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) From Baseline to Weeks 24 and 48 on ART, measured over From baseline (pre-ART and week 0 on ART) to weeks 24 and 48 on ART.

The primary endpoint is change in CD8+ T-cell activation, expressed as the percentage of CD8+ T-cells that are HLA-DR+/CD38+. HLA-DR and CD38 are markers used to identify activated T-cells; the endpoint therefore measures the proportion of the specified cell population carrying both markers. The registry describes the endpoint as a mean change from baseline to weeks 24 and 48 on ART.

Immune activation is relevant to the study’s stated question because the trial was designed to examine whether ART was associated with changes in immune activation among HIV-1 controllers. The endpoint is a biological measure, not a direct measure of symptoms, daily functioning, or a clinical event. It should be interpreted as a measure of the specified cell-marker percentage in the analysis population, rather than as a broad measure of health.

The mean summarizes participants’ changes, while a 95% confidence interval would describe the uncertainty around that estimated mean under the analysis. The registry record identifies the confidence interval as the dispersion measure, but does not report the primary mean change or its interval. It therefore does not allow readers to assess the direction, magnitude, or precision of the primary result from the posted outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the repeated-measures analysis do?

The primary outcome description says the mean change from baseline was estimated jointly for weeks 24 and 48 using repeated-measures analysis. In general, repeated-measures methods are used when outcomes are collected more than once from the same participant. Measurements within a participant tend to be related, so they should not be treated as if they came from unrelated people. An analysis that accounts for this relationship can use the available longitudinal structure to estimate change over time.

The registry identifies generalized estimating equations (GEE) as the method. In general, GEE is a framework for estimating average patterns in a population when observations are correlated, such as repeated observations from participants. Its target is often described as a population-average relationship. The specific GEE model, its working correlation structure, and the variance estimation details are not reported in the registry record, so those aspects cannot be characterized for this study.

The description says the estimates were made jointly for weeks 24 and 48. This indicates that the endpoint concerned follow-up over both listed times, but the registry record does not report the resulting mean change at either time or the joint estimate. It also does not specify whether the reported interval would be for a pooled or otherwise combined contrast beyond the description of joint estimation.

How should the mean and confidence interval be read?

The endpoint is a mean change in a continuous measure: the percentage of CD8+ T-cells defined by the HLA-DR+/CD38+ markers. In general, a mean gives an average across observations in the analyzed population. It can be useful for describing a group-level change, while not implying that every participant had the same change. Variation across participants may be important, but the registry entries do not report a distribution of individual changes.

A 95% confidence interval expresses statistical uncertainty around an estimated quantity under the assumptions of the analysis. In general terms, a narrower interval indicates greater precision than a wider interval, while neither the interval nor its confidence level establishes clinical importance. Interpreting an interval would require the estimate and its endpoints. Those values are not reported in the registry record, so no assessment of precision or compatibility with different possible changes can be made.

What does the analysis population mean?

The registry labels the primary population as as-treated. Participants needed results while receiving ART and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) before week 24 or 48. The description also excludes use of prohibited or precautionary medications based on a team review of concomitant medications. These criteria define who could contribute to the primary analysis; they are not equivalent to simply including everyone enrolled.

In general, an analysis population definition matters because it affects which observations contribute to an estimate and the question that estimate answers. An as-treated analysis focuses on observations under treatment and subject to the stated eligibility conditions. It can differ from an analysis that retains all participants according to an initial assignment. In this single-group study, there was no randomized assignment to preserve for an intention-to-treat comparison. The registry record does not report counts meeting the primary criteria, participant flow by follow-up time, or a comparison of alternative analysis populations.

What can be inferred from the planning illustrations?

The sample-size assumptions describe planning illustrations based on the observed effect, with 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. These are planning assumptions, not a record of this trial’s single-group design, and any resulting sample sizes are illustrations rather than observed power. In general, planning calculations depend on their assumptions; they do not show the probability that a completed study has detected an effect. The registry entries do not report the trial’s own sample-size justification or a numerical planning result to interpret.

Because the trial itself had one group, a hypothetical equal-allocation calculation should not be read as evidence that the study included two arms. Nor does an illustration based on an observed effect provide an independent confirmation of that effect. The effect estimate underlying such planning would need to be reported and interpreted on its own. The primary estimate is not reported in the registry record.

What remains unspecified?

The registry record does not report the full statistical plan, the model’s detailed terms, a missing-data procedure, or whether interim analyses were conducted. Those details should not be inferred from the use of GEE or from the listed confidence-interval type. In general, an analysis method is only one part of a statistical plan: population definitions, outcome timing, missing observations, model specification, and multiplicity decisions can also affect interpretation. Their absence limits how fully the primary analysis can be reconstructed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary CD8+ T-cell activation measure and secondary measures involving viral RNA, CD4+ T-cell count, other immune-activation and inflammatory measures, quality of life, and adverse events. Multiple outcomes and follow-up assessments can create multiple opportunities for statistical findings. In general, multiplicity procedures are used to control or describe the consequences of testing several hypotheses. The registry record does not report a multiplicity adjustment, a hierarchy of secondary outcomes, or a full plan for interpreting multiple comparisons. It is therefore not possible to determine from the record whether multiplicity was addressed in the analysis.

The primary outcome description specifies repeated measures jointly through weeks 24 and 48, but the registry record does not report how missing outcome observations were handled. It also does not give the number of participants with measurements at each time or a detailed account of withdrawals and exclusions. In general, missingness can affect estimates when the availability of measurements is related to participants’ outcomes or circumstances. The registry entries do not establish why any measurements may have been absent or what assumptions the analysis made.

The stated primary analysis population was as-treated and required on-treatment results, suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) before the relevant assessment, and no prohibited or precautionary medications based on team review. The registry record does not report how many participants qualified at each time point or whether other populations were analyzed. It also does not report interim analyses or a detailed statistical analysis plan. These omissions mean that the analysis population and missing-data handling cannot be fully evaluated from the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchitis (2.8%).

The safety record lists 36 participants at risk for serious adverse events and one participant affected. For other adverse events, it lists 36 at risk and 23 affected. The record also lists one death. These are descriptive counts; they do not by themselves show whether an event was caused by FTC/RPV/TDF. The registry entries do not report the circumstances or attribution of the death, so no causal interpretation is warranted.

Bronchitis is listed among the top serious adverse-event terms, with 2.8%. The registry entries do not provide enough context to determine how that percentage was calculated or to infer additional event details. The number of participants at risk is not the same as the number of participants who experienced a particular event, and the serious and other adverse-event counts should not be assumed to be mutually exclusive.

In general, adverse-event counts describe what was recorded during a study; comparison with another group would be needed to make a direct comparative statement about event frequency. This was a single-arm study, so the posted safety figures are not a randomized comparison. They should be read as safety observations in the listed group, not as proof for or against causation.

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

The study addresses a specific statistical question: how the mean percentage of activated CD8+ T-cells changed from baseline to weeks 24 and 48 on ART among participants meeting the as-treated analysis criteria. The registry record provides the endpoint definition and says that repeated-measures GEE was used. It does not report the estimated change or its 95% confidence interval. Consequently, the posted information does not establish whether the measure increased or decreased, by how much, or with what precision.

Even if the outcome estimate were available, the single-group design would remain important. A within-participant change over time describes what happened in the analyzed group; without a separate comparator, it cannot alone isolate the intervention as the cause of that change. This is a general feature of uncontrolled longitudinal studies, not a claim about the unreported outcome in this trial.

The endpoint is a biological measure of immune activation, not a direct measure of symptoms, quality of life, or a clinical event. The registry lists other outcomes, including CD4+ T-cell count, inflammatory biomarkers, quality of life, and safety events, but their presence in the record does not establish their results. No conclusions about those outcomes can be drawn from their names alone.

The listed safety counts provide limited descriptive information: 36 were at risk for serious adverse events, one was affected, 36 were at risk for other adverse events, 23 were affected, and one death was recorded. These counts do not attribute events to the intervention. The serious adverse-event term Bronchitis is listed at 2.8%; the registry entries do not give further context for interpreting that value.

Accordingly, the record supports a description of the study question, design, analysis population criteria, and the safety counts listed. It does not support a conclusion about the primary endpoint result or a causal comparison with no-treatment or alternative-treatment outcomes. The primary result is not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates how a registry record can define a statistical question more clearly than it reports the answer. The primary endpoint is specified as mean change in a cell-marker percentage, the follow-up times are identified, and the analysis is described as repeated-measures GEE. Those details help readers understand what the investigators intended to estimate. Without the mean change and its 95% confidence interval, however, readers cannot evaluate the magnitude or precision of the primary result.

The design also illustrates the difference between observing change and estimating a comparative treatment effect. In a prospective single-group study, participants can be followed from baseline through treatment, but there is no concurrent control group to show what would have happened over the same period under a different condition. This distinction is important when interpreting longitudinal biological outcomes.

The as-treated eligibility criteria further show why the analyzed population matters. The primary endpoint applied to participants with on-treatment results, qualifying viral suppression, and no specified medication concerns after team review. Those criteria define a particular analysis population, and the number meeting them is not reported in the registry record. Enrollment alone therefore does not describe how many observations contributed to each estimate.

The record also lists multiple biological, quality-of-life, and safety outcomes. When several outcomes are considered, a statistical plan can clarify how findings are prioritized and how multiplicity is handled. That plan is not reported in the registry record. Taken together, these features make the record useful for understanding the intended measurement and design while leaving the main numerical result and several interpretive details unavailable.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary outcome estimate and its 95% confidence interval are not reported in the registry record. This is the central limitation for interpreting the study’s primary statistical question: the direction, magnitude, and precision of change in CD8+ T-cell activation cannot be assessed.

The single-group, open-label design has no concurrent control arm. A change from baseline would therefore not, by itself, separate intervention-related change from other changes over time. The absence of masking is recorded, but the registry entries do not describe how this might have affected outcome measurement or participant behavior.

The primary analysis population was restricted to participants with results while receiving ART, with HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) before week 24 or 48, and without prohibited or precautionary medications based on team review. The registry record does not report the number who met these criteria at each assessment, the amount of missing data, or the method used to handle missing measurements. The enrollment of 38 does not establish the analysis denominator for the primary endpoint.

The record identifies GEE and joint repeated-measures estimation, but does not report the model specification, the correlation structure, or detailed variance methods. It also does not report a full statistical plan, multiplicity procedures, interim analyses, or the trial’s sample-size justification. These details cannot be reconstructed from the endpoint description alone.

Finally, the safety counts are descriptive and come from a single group. The registry entries do not provide causal attribution for the listed events or context for the reported death. The listed serious term and percentage do not provide a complete account of event timing, severity, or clinical course.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir — NCT01777997.
• Registry record last updated 2021-08-03; status last verified 2017-12.
• Results first posted 2018-01-12.
• 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

NCT01777997 is a completed, prospective, open-label, single-arm Phase 4 study of FTC/RPV/TDF in treatment-naïve HIV-1 controllers. The registry lists enrollment of 38, a study start of 2013-04-25, and primary completion on 2016-02-19.

The primary endpoint was mean change in CD8+ T-cell activation, defined as the percentage of CD8+ T-cells that were HLA-DR+/CD38+, from baseline to weeks 24 and 48 on ART. The record describes joint repeated-measures estimation using GEE and an as-treated population with stated viral suppression and medication criteria. The primary estimate and 95% confidence interval are not reported in the registry record.

The record lists 36 participants at risk for serious adverse events, one affected, 36 at risk for other adverse events, 23 affected, and one death. Bronchitis is listed among the top serious terms at 2.8%. These safety figures are descriptive and do not establish causation.