Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis (NCT02600819), a non-randomized phase 3 study. The primary outcome is GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48.

2. Clinical Question

This question is descriptive: it concerns the frequency of a defined safety outcome during treatment in the study population. It does not, by itself, estimate how that frequency would differ from a frequency under another regimen or under no treatment. Without a concurrent randomized comparator, differences from other populations or studies could reflect differences in participants, follow-up, clinical care, event definitions, or data collection rather than treatment.

The registry lists HIV-1 RNA outcomes at Week 24, Week 48, and Week 96 as secondary outcomes, alongside pharmacokinetic measures and other safety outcomes. Their results are not reported in the registry record. The primary question therefore remains the safety endpoint as defined in the record, rather than a comparative efficacy question.

3. Trial Design

This is a Phase 3b, open-label, non-randomized, single-group study sponsored by Gilead Sciences. Its official title describes an evaluation of safety, tolerability, pharmacokinetics, and efficacy of E/C/F/TAF in HIV-1 infected subjects on chronic hemodialysis. The record lists the study as completed, with enrollment of 55. It records the start as 2015-12-14 and primary completion as 2017-09-29.

During the GEN phase, participants switched their current antiretroviral regimen to E/C/F/TAF and were scheduled to receive treatment for 96 weeks. The primary safety endpoint covers the period from the first dose through Week 48, so its observation window is shorter than the planned GEN-phase treatment period. The registry record does not report the number of participants who completed each visit or the amount of follow-up contributing to each outcome.

The record also describes an open-label rollover extension. Participants in the United States who wished to participate could continue E/C/F/TAF after Week 96 until the end of the E/C/F/TAF visit. At Week 96 or that end-of-phase visit, whichever occurred last, participants could opt to receive open-label B/F/TAF for at least 48 weeks. The extension is not a randomized comparison: entry was optional, it followed the GEN phase, and the treatments were received in different phases.

“Open-label” means that treatment assignment was not masked, and “single-group” indicates that the primary GEN phase did not include a concurrent control arm in the design described by the record. These features make the registry results useful for describing observed events in the treated study population, but they limit causal comparisons. The registry record does not report a detailed statistical analysis plan, a sample-size justification, an interim-analysis plan, or a randomized allocation procedure. It lists 16 outcome measures and 0 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.

Before assignment: 75 participants were screened.

GEN Phase

Reasons for not completing this period:

BVY OL Extension Phase

Analysis population for the primary outcome, as defined in the registry: The GEN Safety Analysis Set included participants who were enrolled and received at least 1 dose of GEN (E/C/F/TAF FDC).

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: The GEN Safety Analysis Set included all participants who received at least 1 dose of GEN.

6. Primary Endpoint

The registry lists the primary outcome as GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48, measured over First Dose Date Up to Week 48.

The primary endpoint is the percentage of participants experiencing treatment-emergent adverse events graded Grade 3 or higher from the first dose through Week 48. The registry defines treatment-emergent adverse events as events beginning on or after the study drug start date and no later than 30 days after permanent discontinuation of E/C/F/TAF, or all adverse events for participants still taking E/C/F/TAF. Events leading to premature discontinuation are included.

Severity was graded using the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. The record describes Grade 1 as mild, Grade 2 as moderate, Grade 3 as severe, and Grade 4 as life threatening. The endpoint combines events meeting the Grade 3 or higher threshold; it is a participant-level percentage, not a count of all event episodes. A participant with multiple qualifying events would still be represented as a participant experiencing the endpoint, rather than as multiple participants.

Safety endpoints of this kind are used to describe the occurrence of clinically important harms during a specified treatment period. The threshold focuses attention on severe events while retaining a clearly defined observation window. The registry record does not report the primary endpoint result, its uncertainty interval, or the number of participants contributing evaluable data. Consequently, its magnitude and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

It is a binary participant-level outcome: each participant either meets the Grade 3 or higher treatment-emergent adverse-event definition within the specified period or does not. The endpoint is expressed as a percentage of participants, rather than as a rate of event episodes over person-time. This distinction matters because repeated events in one participant do not necessarily count as multiple endpoint participants. The registry describes the population for safety analysis as enrolled participants who received at least 1 dose of E/C/F/TAF, but it does not report the primary endpoint numerator or its analyzed denominator.

How would a percentage be interpreted?

In general, a sample percentage is the observed number of participants meeting the definition divided by the number assessed for that outcome. It estimates the corresponding event proportion in a broader population only under assumptions about how participants entered the study, how outcomes were measured, and how missing observations relate to event status. The percentage is descriptive for the analysis population and time window; it is not a treatment effect unless a suitable comparison is included.

For binary outcomes, uncertainty is commonly expressed with a confidence interval. In general, a confidence interval communicates sampling uncertainty around an estimate, conditional on its statistical method and assumptions. It does not account automatically for bias from selection, unmeasured differences, or incomplete follow-up. The registry record does not report an interval or specify the method used for the primary endpoint. No precision estimate should therefore be inferred from the adverse-event counts alone.

Why does the observation window matter?

The primary endpoint covers events from first dose through Week 48, with the registry’s treatment-emergent definition extending to 30 days after permanent discontinuation for participants who stop treatment. Participants still on treatment have all adverse events included under the definition. This rule defines which events are eligible for the endpoint; it is not simply a count of events occurring at a scheduled Week 48 visit. The exact amount of observation may differ across participants if treatment stops at different times or follow-up is incomplete. Participant-level follow-up and censoring details are not reported in the registry record.

The record lists outcomes at several time points, including HIV-1 RNA outcomes at Week 24, Week 48, and Week 96. In general, repeated assessment times can answer different questions: an outcome at a particular visit describes status at that time, while an outcome over an interval may capture events over a period. These should not be interchanged. The registry identifies the HIV-1 RNA outcomes as using the FDA Snapshot Algorithm, but does not report their results in the registry record for this analysis.

What does the design permit?

The GEN phase is listed as non-randomized and single-group. General statistical interpretation follows from that structure: the observed endpoint can characterize the study participants, but there is no randomized concurrent group to estimate a relative effect. Randomization is one way to balance measured and unmeasured prognostic factors on average between groups. Without it, comparisons with external data or with the optional extension may be affected by differences in participant characteristics, clinical setting, calendar time, selection into the extension, or follow-up.

The extension is a subsequent open-label phase, not a parallel control. Participants could opt to receive B/F/TAF after the E/C/F/TAF period. In general, people entering a later optional phase may differ from those who do not enter, and they have already experienced the preceding study period. Accordingly, the extension figures are useful as descriptive observations for that phase, but they do not provide a clean estimate of the effect of switching treatment.

What methods are documented?

The registry record lists 16 outcome measures and 0 analyses. That entry does not establish that no analysis was performed outside the registry; it means the record does not list analyses in the information considered. The statistical method for the primary endpoint, any adjustment, the approach to repeated observations, and any uncertainty calculation are not reported in the registry record. A sample-size justification, interim analyses, and a detailed statistical plan are also not reported there.

General statistical considerations should not be mistaken for the study’s actual methods. For a binary endpoint, analysts may report an event proportion and an interval reflecting sampling uncertainty. In studies with a suitable randomized comparison, they may estimate a difference or ratio between groups. Those comparative quantities are not warranted by the single-group design unless an appropriate comparison and analysis are documented. No additional result or recalculation can fill in the unreported primary endpoint.

Does over-dispersion apply?

Over-dispersion is a general concern when observed variability in count data exceeds what a chosen probability model expects. It can affect standard errors and confidence intervals in models for counts or clustered observations. The primary endpoint is defined as a participant-level binary percentage, and the registry record does not report a model for it or a cluster structure. There is therefore no basis in the record to claim that over-dispersion was assessed or to describe a correction as having been used. More broadly, statistical assumptions and methods should be identified from the analysis record rather than inferred from an outcome label.

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("E/C/F/TAF (GEN Phase)")
n      <- c(55)
events <- c(18)
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  E/C/F/TAF (GEN Phase)  55  18  32.7  20.7  46.7  21.8  45.9  21.8  46.0

11. Multiplicity, Missing Data and Analysis Populations

The record lists multiple outcomes: the primary safety endpoint through Week 48, safety outcomes at other time points, HIV-1 RNA outcomes at Week 24, Week 48, and Week 96, and pharmacokinetic measures. Considering multiple outcomes can increase the chance that at least one result appears notable by chance if many hypotheses are tested. In general, a prespecified testing hierarchy or a multiplicity adjustment can help manage that issue, while descriptive reporting may instead present estimates without treating each as a confirmatory test. The registry record does not report a multiplicity strategy, testing hierarchy, or detailed statistical analysis plan.

Missing-data handling is also not reported in the registry record. For the primary safety endpoint, incomplete follow-up could affect whether an event was observed during the defined period. The record’s treatment-emergent definition explains which adverse events qualify, including events within 30 days after permanent discontinuation, but it does not describe how participants with incomplete event ascertainment were handled in the analysis. It does not report the primary endpoint denominator, exclusions, or a sensitivity analysis for missing outcomes.

The GEN Safety Analysis Set is described as participants who were enrolled and received at least 1 dose of E/C/F/TAF. This identifies a safety population, but the registry record does not state the endpoint-specific analysis population beyond that description. It also does not report how participants who discontinued, changed treatment, or entered the rollover extension were represented in each outcome analysis.

The registry lists 0 analyses. This is a statement about what the record lists, not evidence that analyses were absent from all study materials. Without reported endpoint results, analysis methods, and missing-data procedures, readers cannot evaluate whether the primary endpoint was analyzed as planned or how sensitive its estimate might be to incomplete follow-up. The reported adverse-event counts remain descriptive summaries, with no documented inferential framework 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: pneumonia (14.5%), hyperkalaemia (10.9%), acute myocardial infarction (10.0%), angina pectoris (10.0%), cardiac failure congestive (10.0%).

For the E/C/F/TAF GEN phase, the adverse-event summary lists 55 participants at risk, 36 with serious adverse events, 41 with other adverse events, and 3 deaths. These are participant counts in the registry summary; they should not be read as counts of event episodes. One participant can experience more than one event, and the record does not clarify overlap between the serious and other adverse-event categories in the registry record.

For the later E/C/F/TAF-to-B/F/TAF extension, the summary lists 10 at risk, 3 with serious adverse events, 10 with other adverse events, and 0 deaths. This was an optional, open-label extension following the GEN phase, not a randomized comparator. The figures should therefore be read as phase-specific descriptive observations, not as evidence that one regimen is safer than the other.

The serious-event terms include Pneumonia, 14.5%; Hyperkalaemia, 10.9%; Acute myocardial infarction, 10.0%; Angina pectoris, 10.0%; Cardiac failure congestive, 10.0%; and Abdominal wall haematoma, 10.0%. These percentages describe the listed terms as reported, but the registry record does not specify their denominator in the registry record for this analysis. The terms do not establish causation, and the listed figures should not be interpreted as comparative treatment risks.

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

The registry record describes a study of E/C/F/TAF in adults with HIV-1 infection receiving chronic hemodialysis, with a primary focus on safety and tolerability. It reports adverse-event counts for the GEN phase and an optional later extension. Those observations provide a descriptive account of events recorded among participants in those phases.

The central limitation is that the registry record does not report the result for the primary endpoint: the percentage experiencing treatment-emergent Grade 3 or higher adverse events through Week 48. It also does not report an uncertainty interval for that endpoint. The available serious-event counts do not substitute for the primary endpoint because the endpoint has a specific severity threshold, event definition, and observation window. As a result, the primary estimate and its precision cannot be assessed from the record.

The study is non-randomized, open-label, and single-group. It therefore does not provide a randomized concurrent comparison from which to estimate how outcomes would differ under another treatment. The optional B/F/TAF extension follows the E/C/F/TAF phase and is not a control group. The registry’s safety summaries cannot establish that a treatment caused an event, prevented an event, or changed event risk relative to an alternative.

The record also lists secondary HIV-1 RNA outcomes and pharmacokinetic measures, but their results are not reported in the registry record. The study title and objectives describe evaluation of efficacy and pharmacokinetics as well as safety, but those aims should not be mistaken for findings. No conclusion about the unreported outcomes follows from the adverse-event summaries.

In general, registry results are most informative when the endpoint definition, analysis population, observed estimate, and uncertainty are all available. Here, the treatment-emergent definition and safety population are described, while the primary endpoint result and several analysis details are not reported in the registry record. The appropriate interpretation is consequently bounded: the posted counts describe reported events, but they do not answer the missing primary endpoint estimate or support a comparative causal conclusion.

14. Why This Trial Matters Statistically

This study addresses a clinically specific population: adults with HIV-1 infection and end-stage renal disease receiving chronic hemodialysis. For statistical readers, the value of examining such a study lies partly in understanding what a registry can and cannot establish when the design is single-group and the primary question concerns safety. The record gives a treatment period, an event definition, and descriptive adverse-event summaries, making the intended safety question identifiable.

The endpoint illustrates why precise definitions matter. “Treatment-emergent” is tied to treatment start and discontinuation, and the primary outcome applies a Grade 3 or higher severity threshold over a defined period. That differs from a broad count of all adverse events and from a count of serious adverse events. Keeping these concepts separate prevents a descriptive safety summary from being misread as the primary endpoint result.

The design also illustrates the limits of phase-to-phase comparisons. The B/F/TAF extension occurs after the GEN phase and is optional. Although the record reports adverse-event figures for both phases, the later group is not a concurrent randomized control. Statistical comparisons between those figures would be vulnerable to selection and timing differences and would not, on their own, identify a treatment effect.

Finally, the record demonstrates the importance of complete reporting. A well-defined endpoint does not permit evaluation of its magnitude or precision when its result and uncertainty are not reported. The listed safety counts are informative as descriptive records, but the primary endpoint result, analysis methods, missing-data handling, and multiplicity approach are not reported in the registry record. Distinguishing documented observations from unreported analyses is essential to a restrained statistical reading.

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 specific limitation is a gap between the primary endpoint definition and the results reported in the registry record. The endpoint is defined as the percentage with treatment-emergent Grade 3 or higher adverse events through Week 48, but its result is not reported in the registry record. The reported serious adverse-event counts cannot be substituted for it, because “serious” and Grade 3 or higher are not identified as interchangeable categories in the record.

The study has no randomized concurrent comparator in its listed design. The single-group GEN phase can describe observed events but cannot separate treatment effects from the underlying clinical course or other influences. The open-label, optional extension is later and follows the GEN phase, so its safety figures do not serve as a like-for-like comparison. Selection into the extension may also affect who contributes those observations; the registry record does not report details that would permit assessment.

The record does not report the primary endpoint’s analyzed denominator, a confidence interval, missing-data procedures, or participant-level follow-up completeness. These omissions restrict assessment of precision and potential bias from incomplete event observation. It also does not report the statistical analysis plan, multiplicity procedures, or a sample-size justification. The registry lists 0 analyses, but that listing alone does not establish what analyses may have been conducted elsewhere.

The serious-event term percentages are reported without the denominator detail available in the registry record. They should therefore be read as registry-listed summaries rather than as independently interpretable risks. The registry entries also do not establish whether reported events were judged related to treatment. These limitations are specific to the record and should not be resolved by assumptions about the protocol or customary practice.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis — NCT02600819.
• Registry record last updated 2020-11-05; status last verified 2020-10.
• Results first posted 2018-10-16.
• 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

NCT02600819 is a completed Phase 3b, open-label, non-randomized, single-group study sponsored by Gilead Sciences. It enrolled 55 adults with HIV-1 infection receiving chronic hemodialysis and evaluated E/C/F/TAF. The GEN phase planned treatment for 96 weeks; an optional open-label extension could involve continued E/C/F/TAF and later B/F/TAF.

The primary endpoint was the percentage experiencing treatment-emergent Grade 3 or higher adverse events through Week 48. The registry describes the event definition and safety population but does not report the primary endpoint result or its precision. It reports descriptive adverse-event counts for the GEN phase and later extension. The record lists 16 outcome measures and 0 analyses. Detailed statistical methods, missing-data handling, and multiplicity procedures are not reported in the registry record.