Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Adults With Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Coinfection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Adults With Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Coinfection (NCT02480712), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

3. Trial Design

This was a phase 3, open-label, single-group study of sofosbuvir/velpatasvir in adults with chronic HCV and HIV-1 coinfection. The registry record lists 107 participants as enrolled and describes treatment with the fixed-dose combination for 12 weeks. The study status is completed. Its recorded start date is 2015-07-01, and primary completion is recorded as 2016-04-29.

Because there was no separate control group, the design is intended to characterize outcomes among participants receiving the study regimen rather than estimate a treatment contrast against another regimen. Allocation is listed as not applicable, and masking is listed as none. The safety record separates participants according to whether their background HIV regimen contained boosted TDF, non-boosted TDF, or no TDF. Those categories do not create randomized arms and should not be read as like-for-like control groups.

The primary endpoint was SVR12, assessed at posttreatment week 12. The full analysis set is defined as all enrolled participants who received at least one dose of study drug. The actual size of that analysis set, the number with endpoint data, and how missing endpoint observations were handled are not reported in the registry record. The primary endpoint result is also not reported in the registry record.

The registry lists secondary outcomes covering SVR4 and SVR24, HCV RNA during treatment and change from baseline, virologic failure, maintenance of HIV-1 RNA below 50 copies/mL while on HCV treatment, and serum creatinine change. Outcome results for these measures are not reported in the registry record. Details of eligibility criteria, treatment adherence, and concomitant-care procedures beyond the described regimen are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 149 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: All enrolled participants who received at least one dose of study drug.

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: Safety Analysis Set: Participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12), measured over Posttreatment Week 12.

SVR12 is the percentage of participants whose HCV RNA is below the lower limit of quantitation 12 weeks after the last dose of study drug. It is a posttreatment virologic endpoint: it assesses whether HCV RNA remains below the assay’s quantitation threshold after treatment has ended, rather than measuring only the change during dosing. The registry record identifies posttreatment week 12 as the timeframe and specifies a 95% confidence interval for the percentage.

As a general statistical concept, a binary endpoint such as SVR12 classifies each participant according to whether the defined response criterion was met. The resulting percentage describes the frequency of that outcome in the analysis population. A confidence interval communicates the uncertainty around an estimated percentage; it does not guarantee that the true value lies within the interval, nor does it remove uncertainty caused by study design or missing observations.

The endpoint is useful for describing a clinically interpretable virologic outcome at a fixed time after treatment. However, the registry record does not report the observed SVR12 percentage, its confidence interval, or the number of participants contributing endpoint data. The endpoint definition alone therefore does not establish the result. Details of the assay, handling of values below quantitation, and rules for classifying missing measurements are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes the study as phase 3, open-label, and single-group. These design labels determine what kinds of statistical conclusions can be supported. The primary outcome is a percentage, and its stated dispersion measure is a 95% confidence interval. The observed percentage and interval are not reported in the registry record.

What does a percentage endpoint estimate?

As a general statistical explanation, a binary endpoint assigns each participant to an outcome category according to a prespecified rule. For SVR12, the rule is HCV RNA below the lower limit of quantitation 12 weeks after the last dose. The percentage is calculated from the participants included in the analysis and with a defined outcome under the analysis rules. The registry record names the full analysis set as enrolled participants who received at least one dose, but does not report the number in that set or the number with evaluable SVR12 status.

A percentage is easier to interpret when its denominator and outcome-handling rules are clear. For example, missing endpoint measurements can affect the denominator or be assigned an outcome under a specified analysis approach. The approach used in this study is not reported in the registry record. It is therefore not possible to reconstruct the primary percentage or determine how missing observations may have influenced it.

How should a confidence interval be read?

As a general statistical explanation, a confidence interval expresses sampling uncertainty around an estimated quantity under the assumptions of the method used. A narrower interval indicates greater precision in that estimate, while a wider interval indicates less precision. An interval does not address all sources of uncertainty: it cannot correct for selection effects, measurement issues, missing-data bias, or the lack of a control group. The registry specifies a 95% confidence interval for SVR12 but does not report its limits or the method used to calculate it.

What does the single-group design allow?

In a single-group study, the primary percentage describes outcomes among participants in the study population. Without a concurrent control group, it does not provide a randomized estimate of the difference between SOF/VEL and another treatment or no treatment. Open-label conduct means treatment masking was absent; the registry does not report whether endpoint assessment was masked. For a laboratory-defined endpoint, the measurement criterion is stated, but details of assessment procedures and quality controls are not reported in the registry record.

The safety categories are based on background HIV regimens: boosted TDF-containing, non-boosted TDF-containing, and non-TDF-containing regimens. The record gives different numbers at risk for these categories. Since allocation is not applicable and the study is single-group, the categories should not be treated as randomized arms. General statistical reasoning cautions that observed differences between nonrandomized subgroups may reflect participant characteristics or other factors rather than the subgroup exposure itself.

What can be said about planning calculations?

The registry record includes assumptions for planning illustrations based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not a description of the trial’s own design or its observed evidence. The record says the illustrations are not the trial’s own design and should not be interpreted as observed power. No illustration values or underlying observed effect are reported in the registry record, and the two-arm planning setup does not change the fact that this clinical study is recorded as single-group.

For general context, planning calculations ask how much information a future study might require under chosen assumptions. They do not measure the probability that a completed study has demonstrated an effect, and a planning scenario based on an observed effect depends on that effect estimate. In particular, it should not be used to fill in an unreported trial result or to infer the precision of the primary endpoint.

What statistical details remain unavailable?

The registry record lists eight outcome measures and zero analyses. It does not report the statistical analysis plan, the method for calculating the confidence interval, any adjustment or stratification, interim analyses, or a sample-size justification for this study. It also does not report the primary result, the number analyzed, or the missing-data approach. Those omissions prevent a detailed assessment of the analysis implementation, even though the endpoint and intended analysis population are described.

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("SOF/VEL 12 Weeks")
n      <- c(106)
events <- c(101)
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  SOF/VEL 12 Weeks  106  101  95.3  89.3  98.5  89.4  98.0  89.4  97.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists eight outcome measures, including SVR12 and several secondary outcomes. It records zero analyses. No multiplicity strategy, such as a hierarchy of testing or an adjustment for evaluating multiple outcomes, is reported in the registry record. Without such a plan and reported analyses, it is not possible to determine whether the outcomes were treated as confirmatory, descriptive, or exploratory, or how any claims across outcomes were intended to account for repeated testing.

Missing-data methods are not reported in the registry record. The primary analysis population is defined as enrolled participants who received at least one dose of study drug, but the number who met that definition and the number with SVR12 data are not reported. The record does not state how participants without a posttreatment measurement were classified, whether any imputation was used, or whether sensitivity analyses were conducted. These details matter because the handling of missing endpoint values can change the estimated percentage and its uncertainty.

The endpoint timeframe is posttreatment week 12, and the endpoint definition is explicit. That definition does not determine how incomplete follow-up was handled. Nor does the record report whether analysis populations differed across primary and secondary outcomes. The primary result, analysis counts, and missing-data approach are all not reported in the registry record, limiting assessment of the robustness of any outcome estimate.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: localised infection (1.8%), sepsis (1.8%), urinary tract infection bacterial (1.8%), radial nerve palsy (1.8%).

The safety record separates participants by background HIV regimen. For the SOF/VEL 12 Weeks group with boosted TDF-containing regimens, 56 participants are listed at risk for serious events and 2 as affected. For the non-boosted TDF-containing regimen group, 35 are listed at risk and 0 as affected. For the non-TDF-containing regimen group, 15 are listed at risk and 0 as affected. These are descriptive counts from a single-group study, not randomized comparisons.

The record lists Localised infection, Sepsis, Urinary tract infection bacterial, and Radial nerve palsy among the serious event terms, each at 1.8%. The registry does not provide further event-level context alongside these entries, so the terms and percentages should not be used to infer causation or compare risk between regimen categories. Death counts are not reported in the registry record.

As a general statistical point, safety counts depend on the population observed, the event definitions, and the length and completeness of follow-up. Additional details about event ascertainment and follow-up are not reported in the registry record. The counts describe the recorded safety information; they do not establish whether an event was caused by study treatment.

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

The study addresses a defined question: the percentage of adults with chronic HCV and HIV-1 coinfection who met the SVR12 criterion after 12 weeks of SOF/VEL. The registry record provides the endpoint definition and identifies the intended full analysis set. It does not report the SVR12 percentage or its 95% confidence interval. As a result, the primary outcome’s magnitude and precision cannot be described from the record.

Even if a single-group percentage is available, its interpretation is descriptive. It characterizes outcomes among participants included in the analysis, but does not estimate a randomized contrast with another regimen. This distinction is important: evidence of an observed outcome within a treated group is not the same as evidence about how outcomes compare under alternative treatment strategies. The study’s open-label, single-group design does not supply a concurrent control group.

The secondary outcomes cover a range of virologic, HIV-related, and laboratory measures. Their results are not reported in the registry record, so their observed values and uncertainty cannot be assessed. Likewise, the available serious-event entries provide counts and listed terms, but not a controlled estimate of treatment-attributable risk. The record does not report death counts.

These limits do not erase the value of a clearly specified question or endpoint. They do mean that the registry record alone cannot establish the observed primary response, assess its precision, or characterize the full balance of efficacy and safety outcomes. Information about missing measurements, analysis methods, and the actual analyzed population would also be needed to judge how robust any reported estimate might be.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a clearly specified endpoint and an unreported endpoint result. SVR12 is defined by a measurable HCV RNA threshold and a stated posttreatment timepoint, and the record specifies a 95% confidence interval. Yet without the percentage, interval limits, or analysis count, the central estimate cannot be evaluated. A well-defined outcome is necessary for interpretation, but it is not a substitute for the observed data.

The design also illustrates why the structure of a study constrains its claims. This phase 3 study is open-label and single-group, with allocation listed as not applicable. Its primary outcome can describe participants who received study treatment, but the design does not estimate a randomized difference against a comparator. The regimen categories used in the safety record are background-treatment groupings, not a control arm.

Another statistical issue is the gap between enrollment and an analysis denominator. The record lists 107 enrolled participants and defines a full analysis set based on receiving at least one dose, but does not report the number analyzed for SVR12 or how missing measurements were handled. Such details are important for interpreting both a percentage and its confidence interval.

Finally, the record lists multiple outcome measures but does not report a multiplicity strategy or outcome analyses. These absences prevent assessment of how findings across outcomes were intended to be interpreted together. The study therefore provides a useful example of how design, endpoint reporting, analysis-population detail, and transparent results all contribute to statistical interpretation.

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.

Several trial-specific limitations of interpretation follow from the registry information. The study had no separate comparator group and was open-label. Its single-group design can describe outcomes among treated participants, but cannot provide a randomized treatment contrast. The background-regimen categories in the safety record are not like-for-like control groups, and the record does not report random allocation among them.

The primary endpoint result is not reported in the registry record. Neither the SVR12 percentage nor its 95% confidence interval is available, and the record does not state how many participants contributed endpoint data. Although 107 participants were enrolled, the full analysis set is defined by receipt of at least one dose, and its size is not reported. Missing-data handling is also not reported.

The registry lists secondary outcomes but does not report their results. It does not report a statistical analysis plan, a multiplicity approach, interim analyses, the method for constructing the primary confidence interval, or a sample-size justification for the trial. These omissions limit assessment of planned inference and analytic robustness. The planning assumptions recorded for illustrations are not the trial’s own design and are not observed-power results.

Safety information is limited to the listed serious-event counts, terms, and percentages. Death counts are not reported in the registry record, and further details about event-level timing, attribution, and follow-up are not reported. These gaps mean that safety entries should be read descriptively and not as a controlled comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Adults With Chronic Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Coinfection — NCT02480712.
• Registry record last updated 2018-11-16; status last verified 2017-04.
• Results first posted 2017-06-01.
• 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

NCT02480712 is a completed phase 3, open-label, single-group study of sofosbuvir/velpatasvir for 12 weeks in adults with chronic HCV and HIV-1 coinfection. The registry lists 107 participants enrolled. The primary endpoint is SVR12, defined as HCV RNA below the lower limit of quantitation 12 weeks after the last dose, with a stated 95% confidence interval.

The primary result and confidence interval are not reported in the registry record. The record lists secondary outcome topics and safety information by background HIV regimen category, including serious-event counts and terms. It does not report the statistical analysis plan, missing-data methods, or the number analyzed for the primary endpoint. The single-group design supports descriptive interpretation rather than a randomized comparison.