Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults (NCT01667731), a non-randomized phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

The study asked whether adults with chronic hepatitis C virus infection and HIV-1 coinfection who received sofosbuvir plus ribavirin achieved a sustained virologic response after treatment. Its primary endpoint was the percentage of participants with SVR12, defined by an HCV RNA level below the lower limit of quantitation at 12 weeks after treatment stopped. The registry record gives the threshold as 25 IU/mL.

3. Trial Design

This was a phase 3, open-label, nonrandomized, parallel-group study sponsored by Gilead Sciences. The registry lists an enrollment of 224 and a completed status. The recorded study start was 2012-07, and primary completion was 2013-11. These registry entries describe the study framework; they do not establish that every enrolled participant contributed data to every endpoint.

All three described groups received sofosbuvir plus ribavirin. Treatment-naive participants with genotype 2 or 3 were assigned to the described 12-week regimen. Treatment-experienced participants with genotype 2 or 3 received the described 24-week regimen. Treatment-naive participants with genotype 1 also received the described 24-week regimen. The descriptions distinguish groups by both HCV genotype and prior treatment experience, so the groups do not represent exchangeable treatment arms.

Because allocation was nonrandomized and masking was absent, the design does not support treating differences among the groups as effects of treatment duration or genotype. Participants were not assigned at random to otherwise comparable regimens, and the group definitions include clinical characteristics that may be associated with outcomes. The record does not report a separate untreated or active-comparator arm.

The study’s stated objective covered efficacy, safety, and tolerability in adults with HCV and HIV-1 coinfection. Secondary outcomes included SVR at posttreatment weeks 4 and 24, changes in HCV RNA during treatment, on-treatment virologic failure, and viral relapse. The registry record does not report results for those outcomes or further details about the statistical design.

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: 330 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: participants who were enrolled and received at least 1 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 were enrolled and received at least 1 dose of study drug

6. Primary Endpoint

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

The primary endpoint was the percentage of participants with sustained virologic response at 12 weeks after discontinuing therapy. SVR12 was defined as HCV RNA below the lower limit of quantitation, stated as 25 IU/mL, at posttreatment week 12. The endpoint therefore classifies each participant according to whether the specified laboratory threshold was met at a defined time after treatment ended.

A sustained response endpoint is used to assess whether a virologic status is maintained after treatment rather than only during active dosing. It is a binary outcome: each participant is counted as meeting or not meeting the definition under the analysis rules. The reported percentage, when available, describes the proportion meeting that definition in the analysis population; it does not by itself describe the size of an individual participant’s change in HCV RNA or establish why a response occurred.

The Full Analysis Set was defined as participants who were enrolled and received at least 1 dose of study drug. The registry record does not report the primary endpoint percentage, its uncertainty interval, or a statistical test. It also does not report how participants without an evaluable posttreatment measurement were handled. Therefore, the endpoint definition and intended population can be described, but the observed SVR12 result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

These methods notes distinguish what the registry record specifies from general statistical interpretation. The record defines a binary primary endpoint and a Full Analysis Set, but it does not report the primary outcome estimate or a detailed statistical analysis plan. The explanations below describe how such outcomes are generally interpreted, not additional analyses performed in this study.

What does a percentage endpoint represent?

SVR12 is a participant-level classification based on whether HCV RNA is below the stated threshold at the specified posttreatment assessment. A percentage for a group would summarize the share of participants classified as meeting that criterion, using a defined denominator. The denominator matters: it depends on who is included in the analysis and on how participants without an observed measurement are handled. The registry record gives the Full Analysis Set definition but does not report the analyzed denominator or missing-data rule for SVR12.

Because the endpoint is binary, the underlying information is the number meeting the endpoint and the number included in the calculation. A percentage alone does not show the distribution of continuous HCV RNA values, the timing of an individual’s response, or whether a threshold result persisted beyond the assessment time. The registry specifies SVR4 and SVR24 as secondary outcomes, but does not report their results.

How should uncertainty be understood?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under the assumptions of the method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval does not account automatically for every source of bias, such as confounding in a nonrandomized study. No confidence interval for SVR12 is reported in the registry record, so precision cannot be assessed from the posted outcome information.

In general, a p-value evaluates how compatible data are with a specified null model under stated assumptions. It does not measure the size or clinical importance of an effect, and it cannot correct limitations in allocation or measurement. The registry record reports no primary-outcome p-value or inferential analysis. With no posted estimate or test, there is no basis for judging statistical evidence from the primary endpoint.

Why does the nonrandomized design matter?

Random allocation is a method for balancing measured and unmeasured prognostic characteristics across treatment groups in expectation. This study’s allocation was nonrandomized, and its cohorts were defined by genotype and prior treatment experience as well as regimen duration. Consequently, comparisons across the groups can mix differences in participant characteristics with differences in treatment exposure. Even if group outcome percentages were available, direct contrasts would not have the same interpretation as a randomized comparison.

Open-label means masking was absent. Lack of masking can matter for outcomes influenced by participant or investigator behavior, assessment, or reporting. The primary endpoint is based on a laboratory threshold, but the registry record does not detail laboratory procedures, assessment processes, or any safeguards against assessment bias. These details should not be inferred.

What does the planning framework mean?

In general, sample-size planning uses assumptions about the outcome, target effect, significance level, allocation, and statistical method to illustrate how much information a study might need. The registry’s stated planning illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it frames the target effect as a stated fraction of the observed effect. This is a planning framework, not evidence that the trial was designed using those assumptions. The registry record does not report the trial’s own sample-size justification. A planning illustration is not observed power and does not replace the missing outcome estimates.

The study itself had nonrandomized groups and no like-for-like control comparison. Thus, assumptions of equal allocation between two arms in a generic planning illustration should not be mistaken for the actual study design. No analysis counts or inferential results are reported in the registry record. The statistical methods that were actually used for endpoint estimation, adjustment, and uncertainty are not reported in the registry record.

Why do repeated outcomes need care?

Multiple endpoints and repeated measurement times create multiple opportunities to observe an apparently unusual result. In general, multiplicity methods define how error across a family of tests is controlled or how findings are interpreted when many outcomes are assessed. The listed secondary outcomes include response at more than one follow-up time and HCV RNA changes at multiple treatment weeks. The registry record does not report a multiplicity strategy. Without one, separate outcome tests should not automatically be treated as a single confirmatory claim.

The record also does not provide a statistical model for the repeated HCV RNA measurements, covariate-adjustment details, or a method for handling incomplete follow-up. Those omissions limit reproducibility and prevent a full appraisal of the statistical analysis. They do not change the stated endpoint definition, but they leave important parts of the analysis approach unreported.

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+RBV 12 Wk GT 2 TN", "SOF+RBV 12 Wk GT 3 TN", "SOF+RBV 24 Wk GT 2 TE", "SOF+RBV 24 Wk GT 3 TE", "SOF+RBV 24 Wk GT 1 TN")
n      <- c(26, 42, 24, 17, 114)
events <- c(23, 28, 22, 16, 87)
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+RBV 12 Wk GT 2 TN  26  23  88.5  69.8  97.6  71.0  96.0  70.8  95.8
ARM  SOF+RBV 12 Wk GT 3 TN  42  28  66.7  50.5  80.4  51.6  79.0  51.5  79.0
ARM  SOF+RBV 24 Wk GT 2 TE  24  22  91.7  73.0  99.0  74.2  97.7  74.0  97.5
ARM  SOF+RBV 24 Wk GT 3 TE  17  16  94.1  71.3  99.9  73.0  99.0  72.7  98.6
ARM  SOF+RBV 24 Wk GT 1 TN  114  87  76.3  67.4  83.8  67.7  83.2  67.7  83.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes in addition to SVR12. These include SVR4 and SVR24, HCV RNA changes at several on-treatment weeks, on-treatment virologic failure, and viral relapse. When multiple outcomes or time points are evaluated, the chance of a notable finding arising by chance can depend on how many analyses are conducted and how their results are interpreted. The registry record does not report a multiplicity adjustment or a hierarchy specifying which secondary outcomes would be confirmatory.

The record defines the primary population as the Full Analysis Set: participants enrolled and receiving at least 1 dose of study drug. It does not report the number with an evaluable SVR12 measurement, whether the analysis used all eligible participants as the denominator, or how missing posttreatment measurements were classified. The handling of withdrawals, incomplete follow-up, and other missing outcome data is not reported in the registry record. These choices can affect a binary endpoint percentage, so the definition of the analysis population alone is not enough to reproduce the estimate.

The record reports 0 analyses. That means it does not present analysis results that would clarify denominators, uncertainty, missing-data assumptions, or adjustment methods. It also does not report an analysis plan detailing covariate adjustment or sensitivity analyses. These omissions limit assessment of robustness and make it inappropriate to infer an analysis method from the endpoint definition or study design.

In general, multiplicity and missing-data decisions should be prespecified and interpreted alongside the observed estimates. Here, those decisions are not reported in the registry record, and the primary outcome result itself is absent. The endpoint can be described, but statistical evidence for it cannot be evaluated from the registry entry.

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: pneumonia (2.4%), chronic obstructive pulmonary disease (2.4%), leukocytoclastic vasculitis (2.4%), cellulitis (1.8%), renal failure acute (1.8%).

The registry lists serious adverse events for each treatment group with a number at risk and a number affected: 5 of 68 in the 12-week genotype 2/3 treatment-naive group, 1 of 41 in the 24-week genotype 2/3 treatment-experienced group, and 8 of 114 in the 24-week genotype 1 treatment-naive group. The record also lists other adverse events, with 57 of 68, 37 of 41, and 106 of 114 affected in those respective groups. These are the posted counts; they should not be treated as randomized comparisons.

The listed serious-event terms and percentages are pneumonia, 2.4%; chronic obstructive pulmonary disease, 2.4%; leukocytoclastic vasculitis, 2.4%; cellulitis, 1.8%; renal failure acute, 1.8%; and acute myocardial infarction, 1.5%. The registry record does not assign these listed terms to specific treatment groups in the information, so group-specific conclusions should not be drawn from them.

Adverse events recorded during a study do not, by themselves, demonstrate that study treatment caused them. The groups differ in their defining characteristics, and there is no randomized control group for a like-for-like safety comparison. Death counts are not reported in the registry record.

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

The study establishes a clear question and a defined endpoint: the percentage of participants meeting a virologic threshold at posttreatment week 12. It also documents treatment regimens for three cohorts of adults with HCV and HIV-1 coinfection. Those design details allow readers to understand which populations were intended to receive each regimen and what outcome the investigators planned to assess.

The registry entry does not report the observed SVR12 result. It therefore does not show how many participants met the endpoint, how the result varied across cohorts, or how precise any estimate was. A study objective, title, or endpoint definition is not an outcome finding. No conclusion about efficacy follows from those elements alone.

The groups also cannot be used as if they were randomized alternatives. Their genotype, treatment-history, and regimen-duration profiles differ, and assignment was nonrandomized. Any observed difference between them, if reported elsewhere, could reflect those population differences or other factors, not solely treatment duration or genotype. The registry information does not permit such factors to be disentangled.

The safety entries describe event counts and selected serious-event terms. They are useful as descriptive registry information, but without a like-for-like control group and fuller analysis details, they do not establish comparative risks or causation. Nor do the posted counts replace reporting of event definitions, timing, severity, or participant-level context.

More broadly, this record is informative about study structure and endpoint definition but incomplete for evaluating the primary result. The analysis denominator, missing-data handling, statistical methods, and uncertainty estimates are not reported. The appropriate interpretation is therefore bounded: the registry describes what was studied and what was intended to be measured, while the primary outcome and its statistical precision remain unreported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why design details are essential when interpreting a clinical outcome. The same combination of drugs was used across three cohorts, but the cohorts differed in genotype, prior treatment experience, and treatment duration. Because allocation was nonrandomized, those groups cannot be treated as interchangeable arms for estimating the effect of one regimen versus another. The design limits what cross-group contrasts could establish, even if outcome estimates were available.

It also illustrates the distinction between a well-defined endpoint and a reported result. SVR12 has a specified measurement time and laboratory threshold, and the analysis population is defined. Yet the registry record does not report the primary outcome percentage or its uncertainty. A precise endpoint definition is necessary for interpretation, but it cannot answer whether the endpoint was met or how reliably an estimate was obtained.

The safety information offers another statistical lesson: counts need context. The numbers at risk and affected are listed by group, but the groups are not randomized comparators. Event counts describe what was recorded; they do not establish a causal treatment effect. The selected serious-event terms are also not assigned to specific groups in the registry information.

Finally, the record identifies several secondary outcomes without reporting the analysis approach, missing-data methods, or multiplicity strategy. These are important for understanding how repeated outcomes and follow-up assessments should be interpreted. Taken together, the study record highlights the value of distinguishing descriptive registry information from comparative inference and of treating absent outcome reporting as a genuine limit on statistical conclusions.

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 main limitation for statistical interpretation is that the registry record does not report the primary SVR12 estimate. It also does not report confidence intervals, p-values, or a detailed analysis of the primary outcome. As a result, neither the size nor precision of the primary result can be assessed from this record.

The nonrandomized design and lack of masking limit causal interpretation. Participants were grouped according to genotype and prior HCV treatment experience, with treatment duration also differing across cohorts. There is no randomized control group, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Comparisons among the cohorts would be vulnerable to differences in their composition.

The registry identifies the Full Analysis Set but does not report the endpoint-specific denominator or how missing SVR12 measurements were handled. It also does not report the trial’s own sample-size justification, detailed statistical plan, multiplicity approach, or sensitivity analyses. The listed planning assumptions are not a substitute for the trial’s design rationale or an observed analysis.

For safety, the registry supplies group-level counts and selected serious-event terms but does not provide enough detail to establish causality or make a randomized comparison. Death counts are not reported in the registry record. The record also does not give further detail on event timing or group assignment for the listed serious-event terms.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults — NCT01667731.
• Registry record last updated 2014-11-21; status last verified 2014-11.
• Results first posted 2014-11-21.
• 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 phase 3, open-label, nonrandomized, parallel study of sofosbuvir plus ribavirin in adults with chronic HCV and HIV-1 coinfection. Enrollment was 224. The three described cohorts differed by genotype, prior treatment experience, and treatment duration.

The primary endpoint was the percentage with SVR12, defined as HCV RNA below 25 IU/mL at posttreatment week 12. The primary analysis population was defined as enrolled participants who received at least 1 dose of study drug. Secondary outcomes included later sustained responses, on-treatment HCV RNA changes, virologic failure, and relapse.

The registry record reports selected adverse-event counts and serious-event terms, but it does not report the primary outcome result, analysis uncertainty, or key details of missing-data and multiplicity methods. Consequently, the record supports description of the study design and planned endpoint, not an estimate of the primary outcome or a causal comparison among groups.