Effects of Biktarvy on CFR in Stable HIV Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Biktarvy on CFR in Stable HIV Patients (NCT03656783), a na phase 3 study. The primary outcome is Change in Global CFR.

2. Clinical Question

The study addresses a cardiovascular imaging measure in people with HIV who have coronary risk factors and were already stable on an antiretroviral regimen containing abacavir. The intervention changes the regimen to one that does not contain abacavir, and the primary endpoint is the change in global coronary flow reserve (CFR), assessed with PET imaging. The record’s summary frames the assessment around removing ABC, but the design does not include a group that continues the previous regimen. As a result, the study can describe changes over time among participants who switch, but the design cannot by itself isolate the effect of the switch from other influences on measurements over time.

3. Trial Design

The registry classifies this study as phase 3, while its official title calls it a pilot study. The record lists a single-group model, no masking, and allocation as NA. It lists enrollment as 25 and status as completed. The sponsor is Brigham and Women's Hospital. The recorded start date is 2018-09-14 and the primary completion date is 2021-09-15.

The enrolled group is described as HIV patients on stable therapy who switched from ABC/3TC/DTG to B/F/TAF. Eligibility included virologic suppression for at least one year and at least one coronary risk factor. The record names current smoking, dyslipidemia, hypertension, diabetes, and obesity among those risk factors; it also mentions a calculated 10-year risk criterion, but the eligibility description ends before stating its threshold. The specified age criteria are men 45 years and over and women 55 years and over.

Because there is no concurrent control group and no random allocation, this is not a randomized comparison of two treatment strategies. Baseline measurements provide a within-participant reference, not a control arm. This distinction matters: changes between baseline and follow-up can reflect the intervention, natural variation, measurement variability, or other changes during follow-up. The registry does not report a masking procedure, consistent with its entry of NONE.

The primary endpoint is assessed at baseline and week 24. The record lists four secondary outcome topics: peak stress global myocardial blood flow, serum biomarkers of inflammation, myocyte injury and strain measured with hs Troponin, and myocyte injury and strain measured with NT-proBNP. It lists five outcome measures overall but no analysis records. The record does not report details of the statistical analysis plan, sample-size justification, or any interim analyses.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: We enrolled men 45 years and over and women 55 years and over with HIV who were stable on a DTG/3TC/ABC regimen with virologic suppression for at least one year, and with at least one coronary risk factor (current smoking, dyslipidemia, hypertension, diabetes, obesity, or a calculated 10-year predicted risk of cardiovascular events of 7.5 percent or over) but without overt cardiovascular disease.

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 Change in Global CFR, measured over baseline and week 24.

The primary endpoint is change in global CFR, expressed as a ratio, measured at baseline and week 24. CFR is defined in the registry record as the ratio of peak vasodilator-stress myocardial blood flow to rest myocardial blood flow. The endpoint is intended to reflect the heart’s ability to increase coronary blood flow and myocardial perfusion under stress. The record states that PET imaging was used and that absolute myocardial blood flow was computed from rest and stress PET images with commercially available software and a two-compartment tracer kinetic model.

The endpoint is a continuous measure, and the registry identifies the reported summary as a mean with a 95% confidence interval. A change score focuses on the difference between follow-up and baseline within the study’s treatment period. The record describes impaired MBFR as a ratio <2.0 and states that this is associated with increased cardiovascular risk. That context explains why the measure is of interest; it does not make the endpoint a direct measure of clinical events or establish that a change in the measure leads to a change in health outcomes.

The registry record does not report the mean change, its confidence interval, the number of participants contributing to the analysis, or a statistical test for this endpoint. Therefore, the direction, size, and precision of the observed change cannot be assessed from the outcome information recorded there.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean change represent?

The primary endpoint is continuous and is summarized as a mean. In general, a mean change describes the average of the within-participant differences between follow-up and baseline for the observations included in an analysis. The mean does not describe every participant’s response: individual changes may vary around the average. A mean can also be influenced by unusually large or small values. The registry record does not provide the observed mean change or the distribution of individual changes, so neither the average nor the extent of variation can be evaluated from the recorded results.

How should a confidence interval be read?

A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. For a mean change, its position indicates which values are compatible with the data and model at the stated confidence level, while its width conveys precision. It is not a range that contains every participant’s change, and it does not indicate the probability that a particular treatment effect is true. In this record, the stated summary is a 95% confidence interval, but its limits are not reported. Therefore, neither precision nor compatibility with any particular value can be assessed.

What is important about a baseline-to-follow-up design?

In general, repeated measurements on the same participants are related rather than independent. An analysis of change should account for that pairing, because each participant contributes measurements at more than one time. A change-score analysis and an analysis that models follow-up while accounting for baseline can answer related questions, but they may differ in assumptions and interpretation. The registry record does not identify the specific model or test used, so it is not possible to determine which approach was used or whether adjustment was made.

Within-participant measurement can reduce the influence of stable differences between participants when estimating change. It does not remove time-related influences that affect measurements during follow-up. Without a concurrent comparison group, changes in CFR cannot be attributed solely to the regimen switch on the basis of the design alone.

Why does the measurement process matter?

CFR is derived from peak stress and rest myocardial blood flow, measured with PET according to the registry description. Because the endpoint is calculated from component measurements, measurement conditions and analytic choices can affect the resulting ratio. The registry describes use of a two-compartment tracer kinetic model and commercial software, but does not report further details about image quality procedures, reader variability, reproducibility, or handling of technically unusable scans. Those details are not reported in the registry record.

In general, measurement error can add variability to a continuous outcome and make an estimated change less precise. Consistent acquisition and processing procedures can support comparability across visits, while differences in procedures can complicate interpretation. The record’s description of the measurement method identifies the general approach but does not supply enough detail to assess its reproducibility in this study.

What can and cannot be inferred from statistical significance?

A p-value, when reported, measures how incompatible the observed data are with a specified null model under its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. A confidence interval is usually more informative for understanding the range of estimates compatible with the data. Neither a p-value nor a confidence interval for the primary endpoint is reported in the registry record, so statistical significance and precision cannot be evaluated.

The record lists two-sided significance level 0.05 as an assumption for planning illustrations. That planning assumption is not evidence that the trial used this threshold in its own analysis. The registry does not report the study’s inferential testing plan or its threshold for judging the primary endpoint.

How should the planning illustrations be understood?

In general, a sample-size illustration asks how many participants per arm might be needed to detect a specified effect under stated assumptions. The record describes illustrations using two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions; they do not turn this single-group study into a two-arm trial, and they do not describe the trial’s observed statistical power. The record does not report the observed primary effect needed to understand an effect-based illustration. No recalculated estimate should be read as the sponsor’s analysis; when the record indicates a discrepancy, the sponsor’s own analysis takes precedence.

Over-dispersion is a general issue for count outcomes: it means that observed variability exceeds what a simple count model assumes, which can make standard errors too small if ignored. The primary CFR endpoint is continuous, not a count, so a count-model explanation does not establish anything about its analysis. The registry record does not provide enough information to determine whether over-dispersion was relevant to any other analysis.

What analysis details remain unknown?

The record does not report the primary analysis model, covariates, handling of missing measurements, analysis population, or whether assumptions were checked. It lists no analysis records. These omissions prevent a full assessment of the statistical procedure, but they do not establish that no analysis was conducted; they mean that analysis details and results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures overall: the primary change in global CFR and secondary measures covering peak stress global myocardial blood flow, inflammation biomarkers, and markers of myocyte injury and strain. Multiple outcomes raise a general multiplicity issue: when many hypotheses are examined, the chance of at least one apparently notable result can increase if no adjustment or prioritization strategy is used. The record identifies a primary endpoint, which distinguishes it from the secondary outcomes, but it does not report a multiplicity procedure, testing hierarchy, or analysis plan. Whether any adjustment was used is not reported in the registry record.

The registry lists no analysis records and does not report results for the listed outcomes. It also does not report the number of participants with usable baseline and week 24 measurements for each measure. The enrollment entry of 25 should not be treated as the analysis denominator without information on follow-up and outcome availability.

Missing data can affect a change analysis if participants with missing follow-up differ from those with observed measurements, or if the reasons for missingness relate to the outcome. In general, complete-case analysis, imputation, and model-based methods rely on different assumptions. The record does not state whether any primary or secondary outcome measurements were missing, how missingness was assessed, or what method was used to address it. These details are not reported in the registry record.

The analysis population is also unspecified. The record does not say whether analyses included all enrolled participants, only those with measurements at both visits, or another defined group. No conclusions about attrition, exclusions, or the effect of missing data can therefore be made from the registry information.

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 non-serious adverse event terms

The adverse-event record lists a group titled “HIV Patients on Stable.” It records 25 participants at risk for serious adverse events and 0 affected by serious adverse events. It also records 25 at risk for other adverse events and 2 affected. Deaths are recorded as 0. No top serious adverse-event terms are listed.

These figures are counts recorded in the registry, not estimates of comparative risk. The study has no concurrent control group, so the entries cannot establish whether events were more or less frequent than they would have been under another regimen. The record does not provide event descriptions for the 2 participants recorded as affected by other adverse events, nor does it provide timing, severity, relatedness, or participant-level detail for those events. No serious-event terms being listed does not provide detail beyond the record’s reported counts.

Adverse-event counts should also be read separately from the primary CFR outcome. They do not explain or substitute for a missing primary result. The registry record does not report additional safety analyses or the procedures used to collect and classify events. Accordingly, the recorded figures describe what the registry lists, not a comprehensive assessment of safety or a causal comparison between treatments.

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

This record describes a study of adults with HIV who were stable on ABC/3TC/DTG and switched to B/F/TAF, with global CFR measured at baseline and week 24. It also describes a PET-based method for assessing CFR and provides background on why the measure may be relevant to cardiovascular risk. These features define the question and measurement approach, but do not themselves establish an outcome.

The result does not establish whether CFR increased, decreased, or remained similar, because the mean change and confidence interval are not reported in the registry record. It also does not establish whether the change was statistically significant or clinically important. The description of impaired MBFR as a ratio <2.0 and its association with increased cardiovascular risk is contextual information; it is not a reported result from this study and should not be used to infer participant outcomes.

The single-group design can describe change during follow-up among participants who switched regimens. It cannot determine, on its own, what would have happened to the same participants over the same period had they continued their prior regimen. Other influences, including natural variation and changes over time, are not controlled by a concurrent comparison group. The study’s focus on a selected population also means the registry description does not establish how findings would apply to people with different characteristics or treatment histories.

The record’s rationale for assessing removal of ABC and its background account of B/F/TAF are not evidence that the switch caused a particular change in CFR. Nor does a cardiovascular imaging measure alone establish effects on clinical cardiovascular events. The registry record does not report such event outcomes as the primary endpoint.

The most defensible interpretation is that the registry documents a planned assessment and a completed study, but not the primary outcome estimate needed to judge the observed change. The adverse-event counts are separately recorded and do not resolve the missing efficacy outcome information. No claim about benefit or lack of benefit follows from the information recorded.

13. Why This Trial Matters Statistically

The study is statistically interesting because it frames a within-participant question around a physiological imaging measure: whether CFR changes from baseline after a switch in antiretroviral regimen. Repeated measurements can be useful for describing trajectories in a selected group, particularly when the outcome is defined consistently at baseline and follow-up. The registry also specifies the CFR construct and gives a broad account of the PET measurement approach, making the intended endpoint interpretable.

At the same time, the design illustrates a central distinction between describing change and attributing change to an intervention. A baseline measurement is not a substitute for a concurrent control group. Without a comparison group, the data would be less able to distinguish a change associated with the switch from other time-related influences. This is a design limitation, not a flaw that can be repaired by statistical significance alone.

The record also shows why outcome reporting is essential to statistical interpretation. Identifying a continuous endpoint and naming a confidence interval does not reveal the effect’s direction, magnitude, or precision unless the result itself is reported. The registry lists no analysis records and does not give the primary outcome estimate. Consequently, readers cannot evaluate the result or compare its uncertainty with a meaningful threshold.

The pilot-study label in the official title and the phase 3 classification in the record underscore the importance of reading study descriptors alongside the actual design and reported analyses. Neither label resolves the lack of a comparator or supplies missing results. The study remains of statistical interest for its question, endpoint, and design, while its evidential contribution cannot be assessed fully from the outcomes recorded.

14. Limitations

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

Several limitations arise specifically from the registry information. Most importantly, the primary CFR change is not reported. There is no mean change, confidence interval, or statistical test to assess. The record lists enrollment as 25 but does not state how many participants completed week 24 or contributed to the primary outcome analysis. It lists no analysis records, so the analysis population and methods cannot be checked.

The single-group design has no concurrent control and no random allocation. As a result, a baseline-to-week-24 change would not separate the effect of switching regimens from other influences over time. The record also lists no masking. The registry does not report whether image assessment or other outcome procedures were blinded.

The eligibility description is truncated after mentioning a calculated 10-year risk criterion, so its threshold is not reported in the registry record. This limits the ability to reconstruct the full eligibility criteria. Although the record identifies the measure and describes its PET-based calculation, it does not report further details on image quality, reproducibility, or handling of unusable measurements.

The record does not report a sample-size justification, interim analyses, a statistical analysis plan, missing-data methods, or multiplicity procedures. The results of the secondary outcomes are also not reported in the registry record. These omissions limit assessment of precision, analysis choices, and the completeness of outcome reporting. They do not establish that these procedures or analyses were absent; their details are simply not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Biktarvy on CFR in Stable HIV Patients — NCT03656783.
• Registry record last updated 2023-02-08; status last verified 2023-01.
• Results first posted 2023-02-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed, phase 3, single-group pilot study sponsored by Brigham and Women's Hospital. It lists enrollment as 25, no masking, and allocation as NA. Participants with HIV who were stable on ABC/3TC/DTG switched to B/F/TAF. The primary endpoint was change in global CFR, measured by PET at baseline and week 24.

The record lists four secondary outcome topics and five outcome measures overall, but no analysis records. It does not report the primary CFR change, its confidence interval, or results for the secondary outcomes. The adverse-event entry lists 0 participants affected by serious adverse events, 2 affected by other adverse events, and 0 deaths. These safety counts are not a randomized comparison.

The registry documents the study question and broad design, but does not provide the outcome statistics needed to determine the direction, size, or precision of the primary change. Analysis methods, missing-data handling, and the full eligibility threshold for calculated 10-year risk are not reported in the registry record.