Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection (NCT01482767), a non-randomized phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24).

2. Clinical Question

The study asked whether a regimen adding boceprevir to the standard treatment described at the time could be evaluated in people living with HIV and HCV coinfection. Its design separated participants according to prior HCV treatment experience rather than assigning them randomly to treatment and control conditions. That distinction shapes what can be learned from the posted results: the record describes experience with the regimen in two clinical-history groups, not a randomized estimate of the effect of adding boceprevir compared with a concurrent control.

The registry lists secondary outcomes involving SVR12, HIV-1 viral load, CD4+ T-cell count, HCV RNA at specified study visits, and adverse events. Those outcomes address different aspects of virologic response, immune status, and safety. Their inclusion does not establish that results for each were posted. The primary endpoint result and the analyses of the listed secondary outcomes are not reported in the registry record.

3. Trial Design

This was a prospective, Phase III, open-label, non-randomized, parallel study. The registry records an enrollment of 262 and lists the study as completed. The start date is 2012-04 and the primary completion date is 2015-04. The sponsor was the National Institute of Allergy and Infectious Diseases (NIAID).

Participants were categorized as HCV treatment-naive in Group A or HCV treatment-experienced in Group B. Both groups began with a 4-week lead-in using pegylated-interferon alfa 2b and ribavirin; boceprevir was added after that lead-in. In Group A, cirrhotic participants received 44 weeks of triple therapy. For non-cirrhotic participants, Week 8 HCV RNA was used to determine total treatment duration, but the remaining description of that regimen is incomplete in the registry record. In Group B, cirrhotic participants received 44 weeks of triple therapy, while non-cirrhotic participants received 32 weeks of triple therapy followed by 12 additional weeks of pegylated-interferon alfa 2b and ribavirin.

Open-label means treatment masking was absent. Non-randomized allocation means the record does not describe random assignment to the groups. Because the groups were defined by treatment history, any differences between them may reflect that history or other differences among participants, rather than a treatment contrast alone. The registry explicitly cautions that the arms are not a like-for-like control comparison.

The record does not report a protocol-level explanation for the allocation approach, a sample-size justification, or an interim-analysis plan. The enrollment figure describes the trial overall; it should not be treated as the denominator for every endpoint. For example, the primary outcome population excludes Group B participants found ineligible after enrollment, while the safety summaries give their own at-risk denominators.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All eligible participants enrolled (Group B participants who were found ineligible after enrollment, n=5, were excluded).

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: All eligible participants enrolled (Group B participants who were found ineligible after enrollment, n=5, were excluded).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response at 24 Weeks After Treatment Discontinuation (SVR24), measured over 24 weeks after treatment discontinuation.

The primary endpoint was the percentage of participants with sustained virologic response 24 weeks after treatment discontinuation (SVR24). The registry defines SVR24 as HCV RNA that was undetectable at that follow-up point: below the assay’s lower limit of quantitation and with target not detected by the Roche COBAS® TaqMan® HCV Test v2.0. Participants without HCV RNA available for the SVR24 determination were counted as not having achieved SVR24.

SVR24 is a binary outcome: each participant is classified as meeting or not meeting the stated response definition, and the endpoint summarizes the percentage meeting it. In general, a follow-up measure after treatment has ended is used to assess whether the virologic response is sustained beyond the treatment period. The registry’s definition is assay-specific and depends on the stated detection criteria, so the result would need to be interpreted in relation to those criteria and the specified follow-up time.

The outcome is described as a percentage, and the registry lists a 95% confidence interval as its dispersion measure. A confidence interval, in general, conveys the precision of an estimated percentage by indicating a range of values compatible with the data and the statistical method used. The registry record does not report the SVR24 percentage or its confidence interval, so the size and precision of the primary result cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on separating the endpoint definition, the population analyzed, the estimate, and its uncertainty. The registry defines the primary endpoint as the percentage of participants achieving SVR24 and names a 95% confidence interval as the measure of dispersion. It does not report an endpoint estimate or interval. Without those results, neither the response percentage nor its precision can be evaluated.

What does a percentage endpoint represent?

For a binary endpoint, each participant is classified into one of two outcome categories. The reported percentage describes the share classified as having the event or response, according to the operational definition. In this trial, SVR24 required HCV RNA to meet the assay-based undetectability definition 24 weeks after treatment discontinuation. The endpoint is therefore not simply any reduction in HCV RNA: it uses a stated threshold and detection criterion at a defined follow-up time.

In general, a confidence interval accompanies an estimate to show its statistical precision. It does not remove uncertainty or guarantee that the true value falls within the particular interval. Its interpretation depends on the method used to construct it and the assumptions behind that method. The registry lists a 95% confidence interval for the primary outcome, but the interval construction method is not reported in the registry record. Because the outcome estimate is also absent, there is no interval to interpret.

Why does allocation matter?

Random allocation is used in general to make treatment groups more comparable in expectation, including with respect to measured and unmeasured participant characteristics. This trial was non-randomized and open-label. The two groups were based on HCV treatment history, not described as randomly assigned treatment conditions. The record also states that the arms are not a like-for-like control comparison. Consequently, group contrasts would not have the same interpretation as a randomized comparison. Differences could be associated with prior treatment experience, other group differences, or the regimens described in the record.

Open-label means there was no masking. In general, knowledge of treatment can influence care, reporting, or assessment, depending on the outcome and study procedures. The primary endpoint uses a laboratory-based HCV RNA definition, but the registry does not report further details about blinding of laboratory assessment or outcome adjudication. Such procedures should not be assumed.

How should missing outcome measurements be read?

The registry specifies that participants without HCV RNA for SVR24 determination were considered not to have achieved SVR24. This is an explicit classification rule for the primary outcome. In general, a rule of this kind affects the numerator and denominator of a binary outcome estimate and can influence its interpretation if missing measurements are common or differ across participant groups. The registry does not report the number of missing SVR24 measurements or a sensitivity analysis showing how alternative assumptions would affect the result. Missing-data handling for the secondary outcomes is not reported in the registry record.

The primary population was all eligible participants enrolled, with Group B participants found ineligible after enrollment, n=5, excluded. This defines who was intended to contribute to the primary endpoint, but it is not enough to determine the number actually assessed at follow-up. The safety summaries use separate at-risk denominators. Population definitions should therefore be read outcome by outcome rather than treating the overall enrollment as every endpoint’s analysis denominator.

What can the planning illustrations establish?

The study’s sample-size material is described as a planning illustration based on the observed effect, not as the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. In general, such calculations illustrate the sample size associated with specified assumptions. They do not show the probability that the completed study detected an effect, and they are not observed power.

The registry record does not report the primary result needed to identify the observed effect, and no numerical planning estimates are reported in the registry record. Therefore, no particular planning sample size or effect scenario can be interpreted from the information posted. The registry also does not report the trial’s own sample-size justification or a formal statistical analysis plan. Those omissions prevent assessment of whether the completed enrollment was selected to address a prespecified precision or hypothesis-testing target.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular relationship between the mean and variability. Over-dispersion occurs when observed variability is greater than that assumed by a model. In general, ignoring it can make standard errors too small and confidence intervals too narrow, leading to overly optimistic assessments of precision. This concept is relevant to count data, but the primary outcome in this trial is a percentage, and the registry does not report a count-model analysis or a method involving over-dispersion. It would not be appropriate to claim that such a model was used.

More broadly, the registry lists several secondary outcomes, but an outcome list is not a statistical analysis plan. The record does not report the statistical tests, adjustment methods, model specifications, or multiplicity strategy for those endpoints. Those details cannot be inferred from the endpoint names, the stated confidence-interval measure, or the study’s Phase III designation.

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("HCV Treatment-Naive (Group A)", "HCV Treatment-Experienced (Group B)")
n      <- c(135, 122)
events <- c(47, 31)
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  HCV Treatment-Naive (Group A)  135  47  34.8  26.8  43.5  27.3  43.2  27.3  43.2
ARM  HCV Treatment-Experienced (Group B)  122  31  25.4  18.0  34.1  18.5  33.8  18.5  33.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcome areas, including SVR12, HIV-1 viral load below 50 copies/mL, change in CD4+ T-cell count, HCV RNA at multiple study visits, and adverse events. When a study evaluates multiple outcomes or time points, the chance of at least one apparently notable finding can increase. In general, a prespecified multiplicity strategy can address that issue. The strategy used for this study is not reported in the registry record.

The primary endpoint population is defined as all eligible participants enrolled, excluding Group B participants found ineligible after enrollment, n=5. For SVR24, participants without HCV RNA for determination were counted as not having achieved SVR24. This is a stated missing-outcome rule, but the number of participants with missing primary measurements and any sensitivity analyses are not reported in the registry record. Missing-data handling for secondary outcomes is also not reported in the registry record.

The registry lists 8 outcome measures and 0 analyses. It does not provide a statistical analysis plan, analysis methods, or a complete account of which participants contributed to each outcome. The safety summaries have their own at-risk denominators, and these should not be assumed to match the primary endpoint population. Without posted outcome analyses, the listed endpoints cannot be used to infer a pattern of efficacy or a multiplicity-adjusted conclusion.

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: neutropenia (7.4%), anaemia (3.3%), overdose (2.2%), asthenia (1.6%), hyperbilirubinaemia (1.6%).

The registry reports serious adverse event summaries for HCV treatment-naive participants in Group A and HCV treatment-experienced participants in Group B. For Group A, 135 participants were at risk and 32 were affected. For Group B, 122 were at risk and 31 were affected. The record also lists other adverse event counts: 135 of 135 at risk in Group A and 120 of 122 at risk in Group B. These are counts as posted; they do not establish that an event was caused by treatment.

The registry lists serious-event terms with percentages: neutropenia, 7.4%; anaemia, 3.3%; overdose, 2.2%; asthenia, 1.6%; hyperbilirubinaemia, 1.6%; and cellulitis, 1.6%. These selected terms should be read as safety descriptions, not as comparative treatment effects. The record does not report death counts. It also does not provide a randomized control group for a like-for-like safety comparison, and the groups differ by treatment history.

In general, adverse-event summaries depend on definitions, ascertainment, and the time period over which participants were observed. The registry lists secondary outcomes involving grade 3 or higher adverse events and grade 2 or higher signs, symptoms, laboratory abnormalities, and other serious events, but detailed analyses of those outcomes are not reported in the registry record. The posted safety counts should therefore be interpreted descriptively.

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

The registry record documents a prospective, Phase III evaluation of boceprevir added to pegylated-interferon alfa 2b and ribavirin among adults with HIV and HCV coinfection. It identifies two groups based on prior HCV treatment experience and specifies SVR24 as the primary endpoint. It also gives an assay-based definition of response and a rule for participants without HCV RNA for the determination. These details clarify what the trial intended to measure.

The primary SVR24 percentage and its confidence interval are not reported in the registry record. Therefore, the posted information does not establish how many eligible participants achieved SVR24, how precise an estimate would be, or how outcomes compare across the groups. The absence of a reported result is not evidence that participants did or did not achieve the endpoint.

The non-randomized allocation and lack of a like-for-like control comparison limit causal interpretation. The two groups were defined by treatment history, and both received regimens involving the study drugs. Any contrast between groups would not isolate the effect of boceprevir. The record does not report a randomized comparison against the standard treatment regimen without boceprevir.

The posted safety counts and selected serious-event percentages describe events recorded in the registry, but they do not establish causation or comparative safety. The record does not report death counts or detailed analyses of all listed secondary outcomes. Overall, the registry supports a description of the study framework, endpoint definitions, population rule, and selected safety summaries. It does not support a conclusion about the primary outcome’s magnitude or a causal treatment effect.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why design and result availability must be considered together. Its Phase III label and enrollment of 262 do not, by themselves, establish that a treatment effect can be estimated or interpreted causally. The non-randomized allocation and the division into treatment-naive and treatment-experienced groups matter because those groups are not a randomized control comparison.

The primary endpoint is carefully operationalized: SVR24 is tied to a specified follow-up time and assay-based undetectability criteria, and participants without HCV RNA for determination are classified as not achieving the endpoint. Such definitions make a binary outcome more reproducible. At the same time, the endpoint definition cannot substitute for the actual outcome estimate, its confidence interval, or information about missing measurements. Those results are not reported in the registry record.

The record also illustrates the difference between an endpoint list and a statistical analysis plan. It names multiple virologic, immune, and safety outcomes, but does not report the analysis methods or a multiplicity strategy. In general, evaluating multiple outcomes requires care when interpreting isolated findings. Here, no outcome analyses are posted in the registry record, so the listed endpoints cannot be treated as evidence of a result.

Finally, the adverse-event counts provide some descriptive safety information but lack a randomized control comparison. The figures need to be read with their separate at-risk denominators and without inferring causation. These features make the study record useful for understanding the intended question and the boundaries of interpretation, while leaving the central efficacy estimate unavailable.

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 posted record is that the primary SVR24 result and its 95% confidence interval are not reported in the registry record. The record lists 0 analyses, so the primary endpoint’s magnitude and precision cannot be assessed from the posted results. Although several secondary outcomes are listed, their results are not reported in the registry record.

The design was non-randomized and open-label. The groups were defined by prior HCV treatment experience, and the registry cautions that they are not a like-for-like control comparison. Consequently, any group difference would not isolate the effect of adding boceprevir. The record does not describe a concurrent randomized group receiving the standard regimen without boceprevir.

The available Group A regimen description is incomplete for non-cirrhotic participants: it states that Week 8 HCV RNA determined total treatment duration, but the remaining details are not reported in the registry record. The registry also does not report the trial’s sample-size justification, the full statistical analysis plan, interim analyses, the methods used to construct confidence intervals, or a multiplicity strategy. These details should not be inferred.

The primary outcome rule classifies participants without HCV RNA for SVR24 determination as not achieving SVR24, but the number of missing measurements and any sensitivity analyses are not reported in the registry record. Safety summaries are descriptive and do not provide a like-for-like randomized comparison; death counts are not reported in the registry record. These limitations constrain assessment of efficacy, precision, missing-data impact, and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection — NCT01482767.
• Registry record last updated 2021-11-04; status last verified 2016-06.
• Results first posted 2016-05-10.
• 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 describes a completed, prospective, Phase III, open-label, non-randomized, parallel study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). Enrollment was 262. The study began in 2012-04, with primary completion in 2015-04, and evaluated boceprevir added to pegylated-interferon alfa 2b and ribavirin in adults with HIV and HCV coinfection.

Participants were grouped by HCV treatment history. The primary endpoint was the percentage achieving SVR24, defined using an assay-based undetectable HCV RNA result 24 weeks after treatment discontinuation. Participants without HCV RNA for the determination were counted as not achieving SVR24. The primary result and confidence interval are not reported in the registry record.

The record lists secondary virologic, immune, and safety outcomes and provides selected adverse-event counts and serious-event terms. It does not report analyses for the listed outcomes, a statistical analysis plan, or a multiplicity strategy. The non-randomized groups are not a like-for-like control comparison.