This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) (NCT03126370), a na phase 4 study. The primary outcome is Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03126370 |
| Phase | Phase 4 |
| Condition | Hepatitis C, HIV Coinfection |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Colorado, Denver |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people living with HIV who are receiving tenofovir-based antiretroviral therapy and a ritonavir- or cobicistat-boosted protease inhibitor. The registry lists hepatitis C and HIV coinfection as conditions. The planned study description says participants were receiving tenofovir disoproxil fumarate (TDF) when invited to participate. The registry record does not report further eligibility details or a demographic description of those enrolled.
Intervention
The treatment phases named in the registry involve TDF with a boosted protease inhibitor, tenofovir alafenamide (TAF) with a boosted protease inhibitor, and TAF with a boosted protease inhibitor plus ledipasvir/sofosbuvir (LDV/SOF). The study asks how plasma tenofovir exposure and renal measures vary across these regimens. The registry describes a five-visit study, including three abbreviated pharmacokinetic visits, and says participants were asked to use a Wisepill device to track medication adherence.
Comparator
The primary endpoint description compares TAF with a boosted protease inhibitor against TDF with a boosted protease inhibitor, and compares TAF with a boosted protease inhibitor plus LDV/SOF against TDF with a boosted protease inhibitor. The registry identifies these as treatment phases, not randomized arms. Consequently, the comparison should not be read as a randomized, like-for-like control comparison.
Primary question
The primary question is whether plasma tenofovir area under the concentration-time curve from time 0 to 24 hours (AUC0-24) changes across the stated phases and timepoints. AUC0-24 represents drug exposure over the measured 24-hour interval. The endpoint is specified at 24 and 28 weeks in relation to week 12. The registry record does not report the observed AUC values, the size or direction of any change, or statistical test results. Therefore, it establishes what was intended to be assessed, but not what the primary comparison found.
3. Trial Design
This is a Phase 4, completed, single-group study with an enrollment of 10. The registry gives a start date of 2018-01-08 and a primary completion date of 2019-07-12. It lists no allocation method and no masking. The record describes treatment phases involving TDF with a boosted protease inhibitor, TAF with a boosted protease inhibitor, and TAF with a boosted protease inhibitor plus LDV/SOF. It does not describe a randomized allocation or a parallel-group control design. The registry specifically cautions that the arms are not a like-for-like control comparison.
The brief description says the study was intended to evaluate the effect of LDV/SOF treatment on tenofovir pharmacokinetics and renal safety in people with HIV receiving tenofovir-based antiretroviral therapy. It outlines five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and an end-of-study follow-up visit. It also says participants were asked to use a Wisepill device to track medication adherence. The registry describes continuation of prescribed treatment for 12 weeks after enrollment in the arm description, but that description is incomplete and does not fully establish the sequence or timing of all treatment phases.
The stated primary endpoint compares plasma tenofovir AUC0-24 between named phases at specified weeks. Secondary outcomes include tenofovir-diphosphate in dried blood spots and renal measures, including estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio (UPCR), and biomarker ratios. Six outcome measures are listed, while no analysis results are listed. The record does not report a statistical analysis plan, a sample-size justification, or details sufficient to establish which participants contributed to each endpoint.
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.
TDF With a Boosted PI
| Stage | TAF With a Boosted PI and LDV/SOF |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
TAF With a Boosted PI
| Stage | TAF With a Boosted PI and LDV/SOF |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
TAF With a Boosted PI and LDV/SOF
| Stage | TAF With a Boosted PI and LDV/SOF |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
TAF With a Boosted PI
| Stage | TAF With a Boosted PI and LDV/SOF |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | TAF With a Boosted PI and LDV/SOF |
|---|---|---|
| Participants analysed | 10 | |
| Age, Continuous | years | 50 (SD 12.3) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 10 |
| eGFR | mL/min/1.73^m2 | 91.5 (SD 26.6) |
| Weight | kg | 88.8 (SD 16.6) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks, measured over 12 weeks and 24 weeks and 28 weeks.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng*h/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is plasma tenofovir AUC0-24, measured in ng*h/mL and summarized using a geometric mean with a geometric coefficient of variation. AUC is the area under a drug concentration-time curve. In general, it represents drug exposure accumulated over a specified observation interval; AUC0-24 covers the interval from time 0 to 24 hours. Pharmacokinetic exposure is used to characterize how much drug is present over time, rather than relying on a single concentration measurement.
The registry describes changes from week 12 at 24 and 28 weeks and specifies comparisons of TAF with a boosted protease inhibitor against TDF with a boosted protease inhibitor, both with and without LDV/SOF in the TAF phase. The record does not provide the actual AUC values, the estimated changes, confidence intervals, or test results. It therefore does not establish whether exposure was higher, lower, or similar across the phases.
A geometric mean is a summary suited to positive measurements that may vary multiplicatively. A geometric coefficient of variation describes relative dispersion around that geometric mean; it is not the same as a standard deviation on the original measurement scale. These summaries help describe both typical exposure and its variability. Their presence in an endpoint definition does not, by itself, show how the phases compared or how precisely any contrast was estimated. The registry record does not report the analysis details needed to interpret an adjusted or unadjusted estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study question and design, but not a conclusion about the primary pharmacokinetic result. It specifies tenofovir AUC0-24 as the primary measure and names comparisons across treatment phases. However, it does not report the observed AUC values, estimated changes, confidence intervals, p-values, or other inferential results. The direction and magnitude of the primary finding are therefore not reported in the registry record. No conclusion about the size or precision of a treatment-phase difference can be drawn from the endpoint definition alone.
The study is listed as single-group, with allocation recorded as NA and masking as none. Its phase comparisons are not described as randomized. In general, nonrandomized comparisons can be affected by differences over time, changes in participants’ circumstances, adherence, or other factors that coincide with a treatment phase. Within-person measurements, if used, may reduce some sources of between-person variation, but the registry does not fully describe the analysis or the participant-level sequence. It is therefore not possible to determine how such factors were handled.
The planned enrollment was 10, and the adverse-event summaries list 10 participants at risk in each named group. These figures do not establish that each group consists of different people. In a single-group study with treatment phases, the same participants may contribute observations across phases, but the record does not make the participant overlap explicit. The adverse-event figures should not be treated as independent randomized-group comparisons.
The registry lists secondary measures of tenofovir-diphosphate and renal function or biomarkers, but does not report their observed values or analyses. Those endpoint descriptions indicate what was intended to be assessed, not whether any measure changed or how precisely it was estimated. Likewise, the record’s completed status indicates that the study is registered as completed; it is not itself evidence of a particular outcome.
In general, an estimate is more informative when accompanied by an uncertainty interval and a clear description of the analysis population and methods. None of those primary-result details is reported in the registry record. The available information is consequently descriptive: it establishes the small study’s question, treatment phases, endpoint definitions, and limited safety counts, while leaving the comparative efficacy and renal findings unresolved.
9. Statistical Methods Explained
The statistical information in the registry is limited. It defines an endpoint and its summary scale, but does not report the methods used to estimate treatment-phase differences or test hypotheses. The registry record lists no analysis results. The explanations below describe general statistical concepts relevant to the stated endpoint; they should not be read as a description of unreported procedures used in this study.
What does AUC measure?
In general, the area under a concentration-time curve combines concentration measurements across a specified interval. AUC0-24 refers to exposure between time 0 and 24 hours. It is a pharmacokinetic measure: it summarizes exposure over time rather than reporting a concentration at one moment. The registry gives the unit as ng*h/mL. The value’s interpretation depends on how concentrations were measured and how the curve was estimated. Those operational details are not reported in the registry record.
Why use a geometric mean?
In general, positive biological measurements can have a right-skewed distribution, with some values substantially larger than others. A geometric mean summarizes multiplicative rather than additive variation and is often used for such measurements. It is formed from the logarithmic scale and expressed back on the original scale. This general property does not establish that a particular distributional assumption was checked or that a particular transformation was used in the study’s analysis.
The endpoint also names the geometric coefficient of variation. In general, this expresses dispersion relative to the geometric mean, making it useful for describing variability on a multiplicative scale. It differs from a standard deviation, which describes spread in the original measurement units. The registry gives no observed geometric means or coefficients of variation, so neither typical exposure nor its variability can be assessed from the endpoint specification alone.
How should a comparison be interpreted?
A comparison between treatment phases needs an estimate of the contrast and a measure of its uncertainty. In general, a confidence interval gives a range of values reasonably compatible with the data and the analysis assumptions. A narrow interval indicates greater precision than a wide interval, although it does not eliminate bias or establish that the study design supports a causal interpretation. A p-value, when reported, summarizes the compatibility of data with a specified null hypothesis under an analysis model; it does not measure the probability that the null hypothesis is true. The registry reports neither confidence intervals nor p-values for the primary endpoint.
Because this is a single-group study without randomized allocation, the named phase comparisons should not be interpreted as randomized comparisons. General threats to interpretation in phase-based comparisons include time-related changes, sequence effects, adherence differences, and other concurrent changes. These are statistical and design considerations, not documented events in this study. The registry record does not report whether they were measured or addressed.
What role does sample size play?
In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, significance level, allocation, and analysis. A planning illustration based on an observed effect is not observed power and does not show that the trial had a particular probability of detecting a true effect. The registry’s stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The record does not report the trial’s own sample-size justification. Because the study is single-group and its comparisons are phase-based, assumptions of equal allocation between two arms are illustrations rather than a description of the registered design.
In general, over-dispersion means that observed variability is greater than expected under a particular model. If a model underestimates variability, uncertainty intervals can be too narrow and tests can appear more decisive than warranted. The registry does not report a model for the primary endpoint or indicate that over-dispersion was assessed. This concept is relevant generally, but cannot be attributed to the analysis of this study.
What analysis details are absent?
The registry does not report the estimator for changes, a statistical test, a confidence-interval method, covariate adjustment, handling of repeated measurements, or assumptions about missing observations. It also does not report analysis populations or participant flow for each endpoint. Without these details, readers cannot determine whether an analysis used paired measurements, how any incomplete pharmacokinetic profiles were handled, or whether the reported geometric summaries were used directly in a contrast.
The record lists six outcome measures but does not describe a multiplicity strategy. In general, evaluating multiple outcomes or contrasts increases the chance that at least one result appears notable by chance if each is tested separately. Methods such as prespecifying a primary contrast or adjusting for multiple tests can address that issue, but the registry does not say whether any such approach was planned or used. As no inferential results are reported, no correction or recalculation can be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary pharmacokinetic endpoint and secondary outcomes involving tenofovir-diphosphate, eGFR, UPCR, and renal biomarker ratios. Six outcome measures are listed in total. It does not describe how multiplicity across outcomes, timepoints, or phase comparisons was handled. In general, testing multiple outcomes or contrasts can increase the chance of a nominally unusual result arising by chance. Prespecifying a primary comparison, using a hierarchy, or applying an adjustment are possible general approaches, but the registry record does not report whether any was used.
The registry record also does not report missing-data rates, reasons for missing measurements, or methods for handling missing pharmacokinetic or renal data. It does not state whether analyses used all enrolled participants, only participants with complete measurements, or another analysis population. The record’s description of a Wisepill adherence device says it was intended to track medication adherence; it does not report adherence results or explain how adherence information entered the analyses.
These absences matter because missing measurements and multiple analyses can affect both the estimated result and its uncertainty. In general, complete-case analysis can be misleading if the availability of measurements is related to participants’ characteristics or outcomes. A multiplicity adjustment may change how results are interpreted when several comparisons are examined. These are general considerations, not evidence that missingness or multiplicity caused a problem in this study. With no posted primary or secondary analysis results, their practical impact cannot be evaluated.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| TDF With a Boosted PI | 0 | 10 | 0.0% |
| TAF With a Boosted PI | 0 | 10 | 0.0% |
| TAF With a Boosted PI and LDV/SOF | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TDF With a Boosted PI | 0 of 10 |
| TAF With a Boosted PI | 0 of 10 |
| TAF With a Boosted PI and LDV/SOF | 0 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| TDF With a Boosted PI | 2 of 10 |
| TAF With a Boosted PI | 2 of 10 |
| TAF With a Boosted PI and LDV/SOF | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|---|
| Renal events deemed possibly, probably or related | Renal and urinary disorders | 2 of 10 | 2 of 10 | 1 of 10 |
The registry reports no serious adverse events and no deaths in any of the three named treatment groups. It lists other, non-serious adverse events affecting 2 participants in the TDF-with-boosted-protease-inhibitor group, 2 in the TAF-with-boosted-protease-inhibitor group, and 1 in the TAF-with-boosted-protease-inhibitor-plus-LDV/SOF group. Each group lists 10 participants at risk. No serious adverse-event terms are listed.
These are descriptive counts, not evidence from a powered safety comparison. The registry does not provide event types for the non-serious events, timing, severity details beyond the serious versus other distinction, or a formal comparison. Because the study is single-group and the treatment phases are not randomized, the group labels should not be assumed to represent independent, concurrent groups. The record does not clarify whether the same participants contributed to more than one group’s count.
Zero reported serious events in these small groups does not establish that serious events cannot occur or that risks are equivalent between phases. It means only that the registry lists no serious events in the reported groups. The adverse-event summary does not replace the missing pharmacokinetic and renal outcome results.
12. What the Result Does, and Does Not, Mean
The registry record identifies a focused pharmacokinetic question: how plasma tenofovir exposure, measured by AUC0-24, varies across phases involving TDF or TAF with a boosted protease inhibitor, and TAF with a boosted protease inhibitor plus LDV/SOF. It also identifies renal safety and several renal measures as study interests. These details show the intended scope of the study, not the direction or magnitude of its findings.
The primary endpoint is defined, but the registry record does not report observed AUC values, estimates of change, confidence intervals, or hypothesis-test results. It therefore does not support a statement that exposure increased, decreased, or remained unchanged. The secondary outcome definitions likewise do not establish a change in tenofovir-diphosphate, eGFR, UPCR, or the stated biomarker ratios. Results for those outcomes are not reported in the registry record.
The study’s completed status and enrollment of 10 describe its registration and size, not the strength of evidence for a treatment effect. Its single-group, nonrandomized design also means that the phase comparisons should not be given the interpretation of randomized comparisons. General concerns such as changes over time or adherence differences may be relevant to a phase-based study, but the registry does not report whether these occurred or how they were handled.
The adverse-event information is limited to counts: no serious events or deaths are listed, and the registry reports other events in the named groups. Those counts are descriptive, and the small enrollment does not establish comparative safety or rule out uncommon harms. A fuller assessment would require outcome estimates, uncertainty measures, methods, and participant-level analysis information, none of which is reported in the registry record. The appropriate interpretation is therefore narrow: the record documents the question and some safety counts, while the principal comparative results remain unavailable.
13. Why This Trial Matters Statistically
This trial is statistically notable for asking a pharmacokinetic question across treatment phases in a small, single-group study, rather than through randomized allocation. That distinction shapes what the comparisons can establish. A measured difference between phases, if reported, would need to be interpreted alongside time, sequence, adherence, and other possible sources of change. The registry record does not report a primary estimate or analysis details, so those issues cannot be weighed against an observed result.
The endpoint uses a geometric mean and geometric coefficient of variation for AUC0-24. These summaries are relevant to positive concentration-derived measures and communicate both typical exposure and relative variability. Their usefulness depends on clearly reporting the observed values and the method used to estimate contrasts. The registry defines the summaries but does not provide the results, leaving the central statistical question unanswered in the record.
The enrollment of 10 also makes precision an important consideration. In general, small studies can yield uncertain estimates, and a lack of a reported difference would not by itself demonstrate equivalence. No uncertainty interval or formal equivalence margin is reported. The registry’s planning-illustration assumptions are not a substitute for the study’s own sample-size justification, which is not reported in the registry record.
Finally, the study combines pharmacokinetic and renal questions and lists multiple outcomes, but its registry entry does not describe multiplicity handling, missing-data methods, or analysis populations. Those omissions make it difficult to evaluate how any eventual results should be interpreted across measures and timepoints. Statistically, the record illustrates why endpoint definitions, study design, analysis methods, and reported estimates are all necessary to judge evidence—not just a completed status or a list of outcomes.
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 limitation for interpreting this trial from the registry record is that the primary and secondary outcome results are not reported. There are no posted AUC values, change estimates, confidence intervals, p-values, or detailed analysis outputs. The endpoint description alone cannot establish the direction, size, or precision of a result.
The study is recorded as single-group, with allocation listed as NA and masking as none. The treatment phases are not described as randomized, and the registry cautions that the arms are not a like-for-like control comparison. Phase comparisons can be affected by time or sequence, among other general concerns; whether these influenced this study is not reported. The arm description is also incomplete, so it does not fully establish the sequence and duration of every treatment phase.
Enrollment was 10. That limited size restricts how much precision and safety information the study can provide, although the registry record does not give a confidence interval with which to quantify precision. It also does not report a sample-size justification. The planning assumptions listed for an illustration should not be mistaken for the trial’s design rationale or for observed power.
Additional limitations include absent analysis details: the record does not report analysis populations, missing-data methods, a multiplicity strategy, covariate adjustment, or the handling of repeated measurements. It does not report adherence findings, although a device was intended to track adherence. Finally, the adverse-event summary lacks descriptions of non-serious event types and does not clarify whether participants overlap across phase groups. These gaps limit interpretation of both the efficacy question and the descriptive safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) — NCT03126370.
- Registry record last updated 2021-02-11; status last verified 2021-01.
- Results first posted 2021-02-11.
- 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.
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18. Record Summary
The registry record describes a completed Phase 4, single-group study with an enrollment of 10, investigating tenofovir pharmacokinetics and renal safety in people with HIV and hepatitis C coinfection. The named treatment phases involve TDF with a boosted protease inhibitor, TAF with a boosted protease inhibitor, and TAF with a boosted protease inhibitor plus LDV/SOF. The primary endpoint is plasma tenofovir AUC0-24, summarized by a geometric mean and geometric coefficient of variation.
The record lists secondary pharmacokinetic and renal outcomes and describes five visits, including three abbreviated pharmacokinetic visits. It reports no serious adverse events or deaths, and lists other adverse events affecting 2, 2, and 1 participants across the three named groups. Primary and secondary outcome estimates, inferential results, analysis methods, missing-data methods, and a trial-specific sample-size justification are not reported in the registry record. The treatment phases are not randomized comparisons, so the record does not support a causal or comparative conclusion about the primary endpoint.