Dutch Acute HCV in HIV Study (DAHHS-2): Grazoprevir/Elbasvir for Acute HCV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dutch Acute HCV in HIV Study (DAHHS-2): Grazoprevir/Elbasvir for Acute HCV (NCT02600325), a na phase 3 study. The primary outcome is SVR12 (Reinfection Not Considered Failure).

2. Clinical Question

3. Trial Design

This was a prospective, open-label, interventional Phase 3 study recorded as completed. It enrolled 80 participants in a single treatment group. The study summary describes the intended population as adults with HIV and acute HCV genotype 1 or 4 infection. Recruitment was planned across 10 HIV treatment centers in the Netherlands and Belgium. The record gives a start date of 2016-02 and a primary completion date of 2018-04-01.

All participants in the treatment group were assigned the grazoprevir/elbasvir single-tablet regimen, listed as 100/50 mg, once daily for 8 weeks. The masking field is listed as none, consistent with the open-label description. Allocation is listed as not applicable because this is a single-group study, rather than a randomized comparison.

The primary outcome was sustained viral response 12 weeks after therapy ended, with reinfection not considered failure. A secondary outcome is also listed: SVR12 with reinfection counted as failure. This distinction matters because the two definitions classify reinfection differently, even though both concern response at the same post-treatment time point.

The registry record marks the study completed, but completion status alone does not indicate what the outcome was. The primary endpoint result, outcome analysis, and statistical analysis details are not reported in the registry record. The record also does not report a concurrent control group or an adjusted comparison. As a result, the design can describe outcomes among treated participants, but does not provide a randomized estimate of how those outcomes differ from an alternative treatment or from no treatment.

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

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 SVR12 (Reinfection Not Considered Failure), measured over 12 weeks.

The primary endpoint is sustained viral response 12 weeks after the end of therapy, assessed among patients who started treatment. The registry describes the primary measure as the number of participants meeting that response definition and states that reinfections are not considered failures. The study summary also describes the intended primary analysis population as the genotype 1 and 4 participants.

SVR12 is used to assess whether a viral response is sustained after treatment has ended, rather than relying only on a response measured while treatment is being taken. In general, a post-treatment endpoint can provide information about persistence of response beyond the treatment period. The registry record does not give further operational details about how viral response was measured, how missing measurements were classified, or how the primary analysis population was finalized.

A second SVR12 outcome is listed with reinfection counted as failure. These are different outcome definitions: a participant with reinfection can be classified differently depending on which definition is used. The registry record does not report the observed count for either definition. It therefore provides the endpoint definitions, but not the results needed to estimate the proportion meeting either endpoint or the precision of those estimates.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the single-group design estimate?

In a single-group study, outcomes are observed in participants who receive the study regimen. A binary endpoint such as meeting or not meeting SVR12 can be represented as a count of participants with the event and a count without it. The record identifies the primary measure as a number of participants, but does not report the observed count. Without that count and a denominator for the analyzed population, an outcome proportion cannot be determined from the registry record.

A single-group estimate is descriptive of the participants included in the analysis. It does not directly estimate a contrast between grazoprevir/elbasvir and another treatment, because no concurrent comparator is listed. Differences from an external expectation or a separate study would require assumptions about comparability; the registry record does not identify such a comparison. This is why the design should not be read as a randomized treatment-effect estimate.

How should uncertainty be understood?

A confidence interval is a range of values compatible with the observed data under a stated statistical method. It communicates the precision of an estimate; it does not guarantee that the true value lies in the interval or account for every source of bias. For a binary response outcome, the interval would depend on the observed number meeting the endpoint and the analysis denominator. Neither the primary endpoint count nor an interval is reported in the registry record, so the precision of the response estimate cannot be evaluated.

A p-value, when used, summarizes how compatible data are with a specified null hypothesis under the assumptions of a test. It is not a measure of clinical importance, nor does it give the probability that a treatment works. The registry record lists no analyses and reports no p-value for the primary endpoint. No inferential conclusion can therefore be drawn from a reported test statistic.

What does the planning illustration represent?

The sample-size assumptions describe planning illustrations based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe hypothetical planning comparisons. They do not describe the actual single-group study design, which has no two-arm allocation. The record does not report the trial's own sample-size justification, and the planning illustrations should not be mistaken for the rationale used to select enrollment.

In general, a sample-size calculation asks how many participants would be needed to detect a specified effect under chosen assumptions. Changing the effect size, variability, significance level, or desired power changes the planning result. These calculations are planning exercises, not estimates of the probability that a completed trial has detected an effect. They are not observed power. Since the registry record does not report an outcome estimate or the numeric planning results, no trial-specific power or required sample size can be inferred from it.

The listed normal approximation is a statistical method for approximating the distribution of an estimate or test statistic. Its suitability depends on the setting and assumptions of the calculation. The registry record does not describe any additional methods used to analyze the trial's endpoint, so the planning assumptions should not be treated as the analysis plan for the completed study.

Why do endpoint definitions matter?

The primary SVR12 definition does not treat reinfection as failure, while the secondary definition does. In general, an endpoint rule determines which participant outcomes count as events and therefore affects the resulting count and estimate. Applying distinct definitions can answer distinct questions about post-treatment response. The registry record does not provide the outcome counts under either rule, explain how reinfection was identified, or specify how participants with missing outcome data were classified.

The record describes the primary endpoint as applying to patients who started treatment, while its study summary calls the intended analysis population the ITT population and identifies genotype 1 and 4. These descriptions indicate the intended focus, but do not give a complete account of the final analysis set or any exclusions. The exact analysis population and handling of deviations are not reported in the registry record.

What can the safety counts show?

Safety counts describe adverse events recorded among participants at risk. They do not by themselves establish that the study regimen caused an event. Causal attribution, event timing, severity details beyond the serious-event classification, and participant-level overlap between categories are not reported in the registry record. A count also does not describe the full clinical circumstances of an event. These considerations apply when reading the serious and other adverse-event figures for this study.

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("Treatment Group")
n      <- c(80)
events <- c(79)
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  Treatment Group  80  79  98.8  93.2  100.0  93.3  99.8  93.3  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary SVR12 definition, which does not count reinfection as failure, and a secondary SVR12 definition, which does. It lists no analyses. The record does not report whether the investigators planned a multiplicity adjustment, a hierarchy among analyses, or a rule for interpreting multiple statistical tests. It is therefore not possible to determine whether or how the possibility of multiple comparisons was addressed.

Missing outcome data can affect a binary endpoint because participants without an observed result must be handled under some analysis rule. Possible approaches include excluding those participants, treating them as failures, or using another prespecified method; these are general examples, not methods attributed to this study. The registry record does not report the number of missing primary outcome measurements, their reasons, or how they were handled. It also does not report whether follow-up was complete for all participants.

The primary endpoint description says it includes all patients who started treatment, and the study summary calls the intended population ITT among genotype 1 and 4 participants. The registry record does not provide a detailed analysis-population definition, participant flow, or the final number included in each endpoint analysis. Thus, the planned enrollment of 80 should not be assumed to be the denominator for the primary result.

The registry record also does not report a statistical analysis plan, prespecified interim analyses, or methods for addressing protocol deviations. The absence of such details in the record does not establish that these procedures were or were not used; their status is not reported 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: traumatic rectal bleeding (1.2%), elective low back surgery (1.2%).

The registry lists 80 participants at risk for serious adverse events and 2 affected participants. It also lists 80 participants at risk for other adverse events and 43 affected participants. The recorded number of deaths is 0. These are safety counts; they do not establish that an event was caused by the study regimen. The registry record does not report event-level timing, causal attribution, or further clinical details.

The top serious adverse-event terms are traumatic rectal bleeding and Elective low back surgery, each listed as 1.2%. The record does not provide enough detail to determine whether these terms refer to distinct participants, how each event was classified in context, or whether either was considered related to treatment. The listed terms should be read as registry safety descriptions, not as evidence of a treatment effect.

Serious adverse events and other adverse events are separate reporting categories in the record; participant overlap between the categories is not reported. Counts do not communicate duration, intensity, or the circumstances in which an event occurred. The registry record also does not report a comparison group, so these safety figures cannot be used to compare event frequency with another regimen or an untreated group.

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

The registry record establishes that the study was designed to examine an 8-week course of grazoprevir/elbasvir in adults with HIV and acute HCV genotype 1 or 4 infection. It also specifies a primary SVR12 outcome and a secondary SVR12 definition with a different rule for reinfection. These details clarify the intended clinical and statistical question, but the record does not report the primary or secondary outcome results.

Without the observed endpoint counts, there is no basis in the registry record for describing the response rate, its precision, or whether the primary endpoint was achieved. A completed study is not necessarily a study with a positive result; completion describes status. The planned enrollment is not a substitute for outcome data, and the safety counts do not answer the efficacy question.

The single-group design can provide descriptive information about outcomes and adverse events in the treated participants if those results are reported. It cannot directly show how those outcomes compare with another treatment, because no concurrent control group is listed. Open-label status also means treatment masking was absent. The record does not describe how the lack of masking affected outcome assessment or whether any protections were used.

The study population is specifically described as adults with HIV and acute HCV genotype 1 or 4 infection. Any interpretation would need to remain tied to that population and setting unless other evidence established broader applicability. The registry record does not report enough outcome or analysis detail to judge the magnitude, precision, or robustness of the treatment response. Its documented purpose and design should therefore be distinguished from a demonstrated result.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way its question and design differ. The registry describes an open-label, single-group study, while the primary endpoint is a binary participant outcome assessed after treatment. That design can produce a cohort-level response count, but it does not provide a randomized contrast against another regimen. The distinction is important when interpreting any single-group result: a response proportion is descriptive unless a suitable comparison and its assumptions are established.

The two SVR12 definitions also show how outcome rules shape analysis. One does not count reinfection as failure, and the other does. Reporting both could make clear how classification affects an endpoint, but the registry record does not provide either result. Without those counts, the statistical implications of the alternative definitions cannot be assessed for this study.

The registry's planning assumptions describe two-arm sample-size illustrations, whereas the actual design is single group. Treating the planning exercise as a trial design or as evidence of observed power would therefore be a category error. The record does not report the trial's own sample-size justification or analysis methods.

Finally, the record separates study completion from available results: the study is marked completed, but the efficacy outcome is not reported. This is a useful reminder that registration details can define a research question without supplying the evidence needed to estimate its answer. For statistical interpretation, design, endpoint definitions, observed data, and uncertainty all matter; only the first two are described in sufficient detail.

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 most important limitation for interpreting the registry record is that it does not report the primary or secondary efficacy outcome results. Without those data, response frequency and precision cannot be assessed. The number enrolled does not reveal how many participants met SVR12, and the completed status does not resolve that information gap.

The single-group design has no concurrent comparator, and allocation is listed as not applicable. Consequently, the design does not supply a randomized estimate of the difference between grazoprevir/elbasvir and another option. The open-label study also did not use masking. The registry record does not report whether outcome assessment was masked in any other way or describe the potential influence of unmasked treatment assignment.

The intended population is restricted to adults with HIV and acute HCV genotype 1 or 4 infection, with recruitment described at centers in the Netherlands and Belgium. Outcomes in this group would not automatically apply to people with other HCV genotypes, people without HIV, or other settings. The record does not report participant characteristics in enough detail to assess representativeness within the stated population.

The record does not report missing outcome counts, reasons for missingness, the final analysis population, or rules for handling missing data. It also does not provide a detailed statistical analysis plan or multiplicity approach. The primary and secondary outcome definitions differ in their treatment of reinfection, but no results under either definition are reported. These gaps limit assessment of analysis choices, robustness, and uncertainty.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dutch Acute HCV in HIV Study (DAHHS-2): Grazoprevir/Elbasvir for Acute HCV — NCT02600325.
• Registry record last updated 2019-07-08; status last verified 2019-04.
• Results first posted 2019-07-08.
• 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.

19. Record Summary

The registry identifies NCT02600325 as the Dutch Acute HCV in HIV Study (DAHHS-2), a Phase 3, completed, prospective, open-label, single-group interventional study. Planned enrollment was 80 adults with HIV and acute HCV genotype 1 or 4 infection. The study summary describes 10 HIV treatment centers in the Netherlands and Belgium.

The treatment group received a once-daily grazoprevir/elbasvir 100/50 mg combination tablet for 8 weeks. The primary endpoint was SVR12 after therapy, with reinfection not considered failure; a secondary SVR12 definition counted reinfection as failure. The registry lists serious adverse events affecting 2 participants, other adverse events affecting 43 participants, and 0 deaths. The efficacy outcome results and detailed statistical analysis are not reported in the registry record.