Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment (NCT01363011), a non-randomized phase 3 study. The primary outcome is Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1).

2. Clinical Question

3. Trial Design

The registry record identifies this as a phase 3, open-label safety study with non-randomized allocation and a parallel-group model. It lists enrollment of 106 and describes two cohorts with different treatment histories and baseline virologic status. Because treatment assignment was not randomized and the cohorts were not alike at baseline, differences between their observed outcomes would not isolate a treatment effect in the way a randomized comparison can.

Cohort 1 included treatment-naive participants who were virologically unsuppressed at baseline. They initiated E/C/F/TDF, a regimen identified in the record as elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate. The treatment description says this regimen was used for up to 96 weeks. Cohort 2 included previously treated participants who were virologically suppressed at baseline. They continued their regimen while switching its pharmacoenhancer from ritonavir to cobicistat and continuing their existing protease inhibitor and two nucleoside reverse transcriptase inhibitors. The full details of this cohort's regimen are not reported in the registry record.

The primary outcome is limited to Cohort 1 and measures change in Cockcroft-Gault estimated glomerular filtration rate from baseline to Week 24. The registry record also lists secondary renal-function outcomes for both cohorts using other estimation equations and later time points. It describes the overall study aim as characterizing renal-function parameters and assessing regimen safety and tolerability.

The primary outcome population is called the Safety Analysis Set and is described as treatment-naive participants who were randomized and received at least one dose of study drug. That wording is inconsistent with the registry record's non-randomized allocation designation. The exact reconciliation of the population wording and the allocation designation is not reported in the registry record. Other details of the allocation process, masking, protocol deviations, and analysis plan 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: 177 participants were screened.

Main Study

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set (treatment-naive only): participants in the treatment-naive group who were randomized and 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 were randomized and received at least one dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Using the Cockcroft-Gault (CG) Equation at Week 24 (Cohort 1), measured over Baseline; Week 24.

The primary endpoint is change from baseline in estimated glomerular filtration rate (eGFR) calculated with the Cockcroft-Gault (CG) equation at Week 24 in Cohort 1. The unit is mL/min. The registry record specifies a median and an inter-quartile range as the endpoint's summary measures, and identifies the analysis population as treatment-naive participants in the Safety Analysis Set who received at least one dose of study drug.

As general statistical background, eGFR is an estimate of kidney filtration rather than a direct measurement of filtration. The CG equation uses patient information to estimate renal function; a change in its estimate can therefore reflect both underlying renal function and the properties of the equation. A change-from-baseline endpoint compares each participant's follow-up measurement with their own baseline value, which can describe the direction and spread of observed changes in the cohort. Reporting a median with an inter-quartile range can be useful when values are skewed or when a small number of observations lie far from the center, because the median is less affected by extreme values than the mean.

The registry record gives the endpoint definition and summary method, but the numerical median change and inter-quartile range are not reported in the registry record. It is therefore not possible to describe the size, direction, or precision of the observed primary outcome from the recorded endpoint information alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what the registry record can establish from what it cannot. The discussion below gives general explanations of those ideas, then relates them to the study details that are recorded.

What does change from baseline describe?

In general, a change-from-baseline endpoint expresses follow-up measurement relative to a participant's starting measurement. Summarizing individual changes can answer a descriptive question about how measurements shifted within the analyzed group. A group median is the central ordered value: values on either side are not necessarily evenly spaced. The inter-quartile range describes the span between the middle portions of the observed distribution and gives a view of its spread. It is not a confidence interval and does not, by itself, quantify uncertainty about the estimated median.

For this study, the primary endpoint is change in Cockcroft-Gault eGFR at Week 24 in Cohort 1, with the median and inter-quartile range specified. The numerical summaries are not reported in the registry record. A confidence interval, if reported, would address uncertainty in an estimated quantity under the method used to calculate it; it would not prove that the estimate is unbiased or that the study design supports causal attribution. No confidence interval for this primary endpoint is reported in the registry record.

Why use different renal-function equations?

As general background, eGFR equations turn clinical measurements into estimates of filtration. Different equations may use different inputs, transformations, and assumptions, so they can yield different estimates for the same participant. Comparing multiple equations can help show whether a pattern is dependent on the estimation method, but agreement across estimates does not make them direct measurements. The registry record lists Cockcroft-Gault and MDRD estimates, as well as cystatin C-based CKD-EPI estimates, including adjusted versions. The actual results for these secondary outcomes are not reported in the registry record, so no agreement or disagreement among them can be assessed.

Why does the non-randomized design matter?

In general, random allocation helps balance measured and unmeasured prognostic factors between groups on average. Without randomization, group membership can be associated with baseline characteristics that also relate to outcomes. Statistical adjustment can sometimes address measured differences, but it cannot guarantee control of unmeasured differences or remove bias from poorly measured factors. In this study, the cohorts differ by prior antiretroviral treatment and virologic status at baseline and follow different regimen strategies. The registry record does not report an adjusted comparative analysis or the details of any confounding-control strategy.

The study is also open-label, meaning masking was absent. In general, awareness of treatment can influence care, reporting, or assessment, although objective laboratory measures may be less directly affected than subjective assessments. The record does not describe how outcome assessment was protected from knowledge of treatment or how adverse events were elicited and classified. Those details are not reported in the registry record.

What do the safety counts mean?

In general, an at-risk count identifies the population considered for a particular adverse-event summary, while an affected count records participants meeting that event definition. Such counts describe what was observed under the study's follow-up and definitions. They do not account for differences in time followed unless person-time methods are used, and do not by themselves establish that treatment caused an event. The record gives at-risk and affected counts for serious and other adverse events in each cohort, but the event definitions, follow-up completeness, and person-time summaries are not reported in the registry record. The record also does not provide a causal comparison between the cohorts.

How should the planning assumptions be read?

General sample-size calculations illustrate how many participants per arm might be needed under selected assumptions to detect a specified effect with a selected probability of statistical significance. They are planning illustrations, not evidence that a study had that probability of detecting an effect after it was conducted. Here, the registry record describes an illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that time-to-event illustrations use total events, while other illustrations use participants per arm. The numerical planning results and the trial's own sample-size justification are not reported in the registry record.

The registry record lists 36 outcome measures and 0 analyses in the information used for this account. A listed outcome is not the same as a reported numerical result or a documented statistical test. The analysis methods, any confidence-interval procedures, distributional checks, missing-data handling, and any prespecified hierarchy of tests are not reported in the registry record. Therefore, statistical significance, precision, and robustness cannot be assessed for the primary endpoint from the endpoint definition and design details alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 36 outcome measures, covering renal-function changes across cohorts, equations, and follow-up times, as well as other outcomes. It reports 0 analyses in the available record. An outcome listing does not establish that each outcome was analyzed, tested, or reported. The registry record does not report whether a primary-versus-secondary testing hierarchy was prespecified, whether multiplicity adjustments were used, or how any multiple comparisons were handled. Without those details and numerical outcome results, the chance of false-positive findings across a set of tests cannot be evaluated.

Missing-data methods are also not reported in the registry record. The available information does not state how many participants contributed measurements at each visit, whether participants discontinued, how missing follow-up values were handled, or whether analyses used imputation or other assumptions. These details matter because a change-from-baseline estimate can be affected if participants with missing follow-up differ systematically from those with observed measurements. The endpoint description names a Safety Analysis Set, but does not provide enough information to assess the completeness or representativeness of that set at Week 24.

The primary population description includes the phrase “randomized and received at least one dose,” while the study allocation is identified as non-randomized. The record does not explain this wording. It also does not report whether analyses were based on an intention-to-treat population, a per-protocol population, or another prespecified set beyond the stated Safety Analysis Set. The registry record does not report interim analyses, a complete statistical analysis plan, or a sample-size justification for the trial. The absence of these details limits assessment of prespecification and the potential influence of analysis choices.

11. 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: anaemia (3.0%), right ventricular failure (3.0%), hepatitis c (3.0%), infected cyst (3.0%), blood creatine phosphokinase increased (3.0%).

The registry record reports serious adverse events for Cohort 1 as 6 affected participants among 33 at risk, and for Cohort 2 as 11 among 73 at risk. For other adverse events, it reports 31 among 33 at risk in Cohort 1 and 66 among 73 at risk in Cohort 2. These figures describe the reported counts within each cohort; they should not be interpreted as proof that a regimen caused or prevented an event. The cohorts were non-randomized and differed in treatment history and virologic status at baseline, so their counts are not a like-for-like comparison.

The record lists anaemia, right ventricular failure, hepatitis C, infected cyst, increased blood creatine phosphokinase, and diabetes mellitus as serious-event terms, each at 3.0%. In the available information, the terms are not assigned to a specific cohort, and their corresponding participant counts are not reported. The record does not describe event severity criteria, duration of follow-up for these summaries, or whether repeated events in one participant were counted separately. Deaths are not reported in the registry record. These limitations mean the listed counts and terms should be read as descriptive safety reporting, not as a comparative risk estimate.

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

The study addresses renal-function estimates and safety in people with HIV infection and mild to moderate renal impairment who received cobicistat-containing regimens. Its primary outcome is defined as change in Cockcroft-Gault eGFR from baseline to Week 24 in treatment-naive Cohort 1. That endpoint definition identifies the clinical measurement and analysis group, but the numerical median and inter-quartile range are not reported in the registry record. The posted information therefore does not show the observed direction, magnitude, or variability of the primary outcome.

The design cannot support a simple causal comparison between the cohorts. Allocation was non-randomized, and the cohorts began with different treatment histories and virologic status. They also followed different regimen strategies. Thus, observed differences would not be attributable to the regimen alone on the information available. The registry record does not report a randomized control comparison or an adjusted analysis that would address these differences.

The listed renal outcomes suggest that the study assessed more than one eGFR equation and follow-up time. In general, such measures can provide complementary descriptions, but estimated values from different equations need not be identical. Because the numerical secondary results are not reported in the registry record, they cannot establish whether results were consistent across equations, cohorts, or visits.

The adverse-event counts document reported events in the two cohorts, and several serious-event terms are listed with a reported percentage. They do not establish comparative safety or causation in this non-randomized design. The available record does not provide enough information about follow-up time, event definitions, missingness, or the assignment of individual serious-event terms to cohorts to support more detailed interpretation.

In short, the registry record establishes the study's broad design, cohort descriptions, endpoint definitions, and selected safety counts. It does not provide the primary renal outcome values, inferential results, or enough analysis detail to quantify uncertainty or draw a causal treatment conclusion.

13. Why This Trial Matters Statistically

This study is statistically notable for the way its clinical question is framed around change in a renal-function estimate rather than a randomized between-treatment contrast. A baseline-to-follow-up measure can be informative about the course of a cohort's estimated renal function, but interpretation depends on the actual distribution of changes, completeness of follow-up, and the population included in the analysis. Those numerical results and details are not reported in the registry record.

The parallel cohorts also illustrate why clinical similarity matters when comparing groups. Cohort 1 was treatment-naive and virologically unsuppressed at baseline, whereas Cohort 2 was previously treated and virologically suppressed. Their treatment strategies differed as well. Since allocation was non-randomized, any comparison across cohorts could combine regimen-related differences with differences in baseline prognosis and treatment history. The registry record itself cautions that the arms are not a like-for-like control comparison.

The use of multiple eGFR equations is relevant because renal function is represented by estimates rather than a single direct measure in these endpoints. Looking across equations may help characterize how an observed pattern depends on the estimation approach, but it also creates multiple outcomes whose interpretation depends on prespecified analysis and reporting choices. Those choices and the numerical findings are not reported in the registry record.

Finally, the distinction between safety counts and comparative evidence is important. The recorded counts can describe adverse events observed within each cohort, but the design and reported detail do not permit a reliable causal contrast. The trial's statistical contribution can therefore be understood through its endpoints and descriptive safety reporting, while its limits for comparative inference remain central.

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 the posted results is that the registry record defines the primary endpoint but does not report its numerical summary. The median change and inter-quartile range for Cohort 1 at Week 24 are not available in the record used for this analysis. Numerical results for the listed secondary renal outcomes are also not reported in the registry record, preventing assessment of direction, magnitude, precision, or consistency across equations and time points.

The non-randomized design creates a further limitation for comparative interpretation. The two cohorts differed in prior antiretroviral exposure and virologic status, and their regimen strategies were not alike. A difference between cohorts could therefore reflect baseline or treatment-history differences rather than a regimen effect. The registry record does not report a randomized comparator or a statistical adjustment sufficient to address this concern. The open-label design also leaves masking-related assessment details unreported.

Important analysis information is absent from the registry record, including the handling of missing measurements, follow-up completeness at each visit, confidence intervals, and the statistical methods used for the endpoint. The stated primary population description refers to participants who were randomized, despite the non-randomized allocation designation; this inconsistency is not explained. The record does not report a complete analysis plan, multiplicity strategy, interim analyses, or the trial's own sample-size justification.

Safety interpretation is limited by the lack of detail on event definitions, time at risk, event-level cohort attribution for the listed serious terms, and deaths. The reported counts remain descriptive and do not establish causation. These limitations are specific to the recorded design and results information and should be considered when interpreting any treatment-related claims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment — NCT01363011.
• Registry record last updated 2016-05-02; status last verified 2016-03.
• Results first posted 2014-10-31.
• 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.

18. Record Summary

The registry record describes NCT01363011 as a completed phase 3, open-label, non-randomized parallel study sponsored by Gilead Sciences. It lists enrollment of 106 and concerns cobicistat-containing antiretroviral regimens in people with HIV infection and mild to moderate renal impairment. Cohort 1 included treatment-naive participants who were virologically unsuppressed at baseline and initiated E/C/F/TDF. Cohort 2 included previously treated, virologically suppressed participants who switched their pharmacoenhancer from ritonavir to cobicistat while continuing their existing protease inhibitor and two nucleoside reverse transcriptase inhibitors.

The primary outcome is change from baseline in Cockcroft-Gault eGFR at Week 24 in Cohort 1, summarized by a median and inter-quartile range. Its numerical result is not reported in the registry record. The record lists 36 outcome measures and 0 analyses. It reports serious adverse events in both cohorts and names several serious-event terms, but the available information does not support a causal comparison between the non-randomized cohorts. The registry record also notes that the arms are not a like-for-like control comparison.