A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients (NCT00838162), a randomized phase 2 study. The primary outcome is Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA).

2. Clinical Question

3. Trial Design

This was a Phase IIa, randomized, open-label, parallel-group trial in treatment-naive participants with HIV-1 infection. The trial evaluated 14 days of monotherapy with four TMC310911 dose regimens, each coadministered with ritonavir. The registry lists enrollment of 33 and gives the trial status as completed. The recorded start is 2009-06, and primary completion is recorded as 2009-08.

The four regimens differed in the TMC310911 dose or dosing frequency, with corresponding ritonavir schedules: 75 mg twice daily with ritonavir 100 mg twice daily; 150 mg twice daily with ritonavir 100 mg twice daily; 300 mg twice daily with ritonavir 100 mg twice daily; and 300 mg once daily with ritonavir 100 mg once daily. The record describes assignment to parallel groups, but does not report the randomization method, allocation ratio, or group sizes for the primary outcome.

Masking was listed as none, so the trial was open-label. The registry record does not report whether outcome assessment or laboratory measurement was blinded. The primary outcome was mean change from baseline in plasma HIV-1 RNA at Baseline (Day 1), Day 8, and Day 15. The defined primary-outcome population was the intent-to-treat population, consisting of participants who received at least 1 dose of TMC310911. The record does not report details about adherence or the number included in each timepoint analysis.

The sponsor was Tibotec Pharmaceuticals, Ireland. Secondary outcomes included virologic response at any timepoint during treatment, CD4+ cell-count changes, and several TMC310911 pharmacokinetic measures. A detailed protocol, statistical analysis plan, randomization procedures, and sample-size justification 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: In total, 41 participants were screened of whom 33 participants were randomized and treated with TMC310911. All treated participants completed the study; there were no dropouts or discontinuations during the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent-to treat (ITT) population- participants who received at least 1 dose of study medication (TMC310911).

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 Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA), measured over Baseline (Day 1), Day 8, Day 15.

The primary endpoint is mean change from baseline in plasma HIV-1 RNA, measured in log10 copies/mL. The named measurement times are Baseline (Day 1), Day 8, and Day 15, spanning the 14-day treatment period. The outcome description frames the endpoint as a measure of antiviral activity after treatment initiation.

In general, HIV-1 RNA is a quantitative marker of viral concentration in plasma. Assessing its change from baseline describes how the measured value shifts over time relative to the participant’s starting value. Using a mean summarizes the average change within the analyzed group. This can make the overall pattern easier to describe, although a group mean does not show how much individual participants’ responses varied.

The registry identifies standard error as the measure of dispersion for the mean. In general, a standard error describes the sampling uncertainty around an estimated mean; it is not a measure of the spread of individual observations. The numerical mean changes and standard errors are not reported in the registry record, so neither the direction nor magnitude of the endpoint changes can be described from the available information. The record also does not give confidence intervals or a numerical comparison between regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

For a continuous outcome such as plasma HIV-1 RNA, a mean change summarizes the average difference between measurements at follow-up and baseline within the group being analyzed. It is a group-level summary: it does not indicate that every participant changed by the same amount, or even in the same direction. Individual observations may vary around the mean.

The endpoint is stated in log10 copies/mL. In general, a logarithmic scale expresses values on a transformed scale rather than as raw counts. Interpretation should therefore stay with the stated measurement scale unless a result is explicitly converted and the conversion is reported. No such conversion or numerical endpoint estimate is reported in the registry record.

What does the standard error tell a reader?

The registry identifies standard error as the dispersion measure accompanying the primary mean. In general, standard error reflects the precision of an estimated mean under the assumptions of the analysis. A smaller standard error indicates a more precisely estimated mean, while a larger one indicates greater sampling uncertainty. It does not describe the full spread of individual participant values; a standard deviation is commonly used for that different purpose.

A confidence interval is a range constructed by a statistical procedure to represent uncertainty around an estimate. In general, it helps readers judge which values are compatible with the data and the chosen confidence procedure. The registry information used does not report confidence intervals for the primary outcome. Without an estimate and an uncertainty measure, the precision of the mean changes cannot be evaluated.

How does the design shape comparisons?

Randomized allocation is intended, in general, to reduce systematic differences between groups at the point of assignment. A parallel-group design assigns participants to a regimen and follows those groups rather than having each participant receive each regimen in sequence. The record identifies this trial as randomized and parallel, but does not report the randomization process, allocation ratio, or group sizes for the primary endpoint.

Open-label means masking was listed as none. In general, awareness of assigned treatment can influence participant-reported outcomes, clinical decisions, and some aspects of outcome assessment. The primary endpoint is a laboratory measure, but the registry information does not say whether laboratory personnel were blinded or describe other protections against assessment bias. It would therefore be unwarranted to assume either blinded or unblinded laboratory assessment.

The four regimens allow the study to examine outcomes under different TMC310911 doses and dosing frequencies, each with a stated ritonavir schedule. A comparison across groups would require the group-specific outcome estimates and a prespecified or otherwise clearly described analysis. Those estimates and the statistical comparison method are not reported in the registry record. A difference between group means, if reported, would also need an uncertainty estimate to distinguish the estimated size from its precision.

What can be inferred from the planning assumptions?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for effects expressed as a fraction of the observed effect. These are assumptions for an illustrative calculation, not evidence about the trial’s actual power or a record of its design justification.

The numerical planning estimates and the observed effect used for them are not reported in the registry information used for this analysis. No sample-size calculation can therefore be interpreted from the assumptions alone. In general, sample-size planning estimates depend on assumptions about the effect to detect, variability, significance level, allocation, and analysis. A planning illustration is not observed power: it does not measure the probability that a completed trial detected an effect, nor does it substitute for reported estimates and uncertainty.

Why do multiple outcomes and timepoints matter?

The primary outcome includes measurements at multiple times, and the registry lists additional virologic, immunologic, and pharmacokinetic outcomes. In general, examining multiple outcomes or timepoints creates multiple opportunities to observe apparently notable results by chance. Statistical methods may address this through a prespecified testing hierarchy, adjustment, or a clear distinction between primary and exploratory analyses. The registry record does not report a multiplicity strategy or a detailed statistical analysis plan, so it is not possible to determine how these issues were handled.

Likewise, interpreting repeated measurements requires knowing how within-participant correlation and incomplete observations were handled. The record does not report the model used for repeated measurements, whether estimates were adjusted, or how missing outcome data were treated. These are general considerations, not claims about methods used in this trial. The stated endpoint, design, and population definition establish what was intended to be assessed; they do not establish the analytical details or the numerical findings.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was measured at Baseline (Day 1), Day 8, and Day 15, and the registry lists additional secondary outcomes. In general, multiple outcomes and assessment times raise multiplicity concerns: the more comparisons examined, the greater the chance that a seemingly notable finding may arise by chance. A prespecified hierarchy or adjustment can help define how evidence is interpreted, but the registry record does not report a multiplicity approach, a testing hierarchy, or a detailed statistical analysis plan.

Handling of missing data is also not reported in the registry record. It does not state whether all participants had measurements at each timepoint, what caused any missing measurements, or whether any imputation or other missing-data method was used. Without those details, the impact of incomplete observations on the estimated mean changes cannot be assessed.

The primary-outcome population is described as intent-to-treat and includes participants who received at least 1 dose of TMC310911. The registry does not report the number analyzed at each timepoint or whether any additional analysis populations were used. It also records zero analyses, which means analyses are not listed in the registry record; it does not establish that the investigators performed no analyses. Results by population, and any analysis adjustments, are not reported in the registry record.

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 non-serious adverse event terms

The adverse-event record lists four regimen groups. For serious adverse events, each group reports zero affected participants: the 75/100 mg twice-daily regimen had 9 at risk, the 150/100 mg twice-daily regimen had 8 at risk, the 300/100 mg twice-daily regimen had 8 at risk, and the 300/100 mg once-daily regimen had 8 at risk. The record lists no serious-event terms. These are the posted serious-event counts for the recorded groups; they do not establish that the risk of a serious event is absent.

For other adverse events, the record reports 5 affected among 9 at risk in the 75/100 mg twice-daily group, 5 among 8 at risk in the 150/100 mg twice-daily group, 6 among 8 at risk in the 300/100 mg twice-daily group, and 3 among 8 at risk in the 300/100 mg once-daily group. These counts should be read as registry entries for affected participants, not as a measure of event severity or duration. The record does not provide the event terms for these counts in the information used.

Deaths are not reported in the registry record. The safety counts alone do not establish comparative safety, particularly without event details, duration of observation, or a reported statistical comparison.

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

This trial’s stated purpose was to assess antiviral activity during 14 days of treatment with four TMC310911 and ritonavir regimens in treatment-naive participants with HIV-1. The primary measure was mean change from baseline in plasma HIV-1 RNA at the named assessment times. The design and endpoint describe the question the study set out to address; they do not, on their own, establish the outcome.

The registry information used for this analysis does not report the primary mean changes, standard errors, confidence intervals, or tests. It therefore does not support a conclusion about the direction or magnitude of change, the precision of the estimates, or differences between regimens. The listed secondary outcomes likewise cannot be interpreted without their numerical results. A completed trial status should not be treated as evidence for a particular result.

In general, a short-term change in a laboratory marker is a statistical outcome measured over a defined period. It is not, by itself, a complete account of longer-term outcomes or an evaluation of every aspect of a regimen. This study’s recorded treatment period was 14 days; longer-term follow-up is not reported in the registry information used. The record also does not provide enough information to assess how broadly its findings might apply beyond the described population.

The safety counts show the recorded numbers of participants affected by serious and other adverse events in the four groups. They are descriptive counts and do not supply event-level details or a comparative safety analysis. Overall, the registry supports a description of the trial’s design, intended endpoint, and reported safety figures, but not a judgment about the primary response or comparative clinical effects.

13. Why This Trial Matters Statistically

This trial is statistically notable for setting out a randomized comparison of four dose schedules over a defined short treatment period. The primary endpoint was a continuous measure, mean change in plasma HIV-1 RNA on the log10 copies/mL scale, assessed at stated timepoints. Such an endpoint can summarize average change, while its uncertainty and the distribution of individual responses are needed for a fuller interpretation.

The design also highlights the distinction between a question and an answer. Randomization and a parallel-group structure define a way to compare assigned regimens, but a meaningful statistical interpretation requires group-specific estimates, uncertainty, and a description of the analysis. Those outcome estimates and analysis details are not reported in the registry information used. The design alone cannot establish the size or precision of any difference.

Multiple timepoints and secondary outcomes make clear why analysis plans matter. General statistical practice calls for readers to understand which outcomes were primary, how comparisons were defined, and whether multiplicity and missing observations were addressed. The registry identifies a primary outcome and several secondary outcomes, but does not report a detailed statistical plan or missing-data methods.

The record’s safety counts also illustrate the limited role of descriptive event numbers. Counts can communicate what was recorded in each group, but without event details and a comparative analysis they do not quantify a treatment contrast or its uncertainty. Together, these features make the trial a useful example of why registry design information and numerical outcome reporting are both necessary for statistical interpretation.

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 main limitation for interpreting the primary endpoint is that its numerical results are not reported in the registry information used. Without group-specific mean changes and standard errors, the size, direction, and precision of changes cannot be assessed. No confidence intervals or formal comparisons between regimens are reported.

The treatment period was 14 days. This defines the scope of the stated primary question but does not provide information about longer-term outcomes; longer-term follow-up is not reported in the registry record. The trial was open-label, with masking listed as none. Whether laboratory assessment was blinded is not reported in the registry record.

Although the registry describes a randomized parallel-group design, the randomization procedure, allocation ratio, and primary-outcome group sizes are not reported. Enrollment was 33, but enrollment alone does not show how many participants contributed measurements at each timepoint. The record does not report missing-data methods, adherence, or the reasons for any incomplete observations.

The registry lists several timepoints and secondary outcomes, but a multiplicity strategy and detailed statistical analysis plan are not reported. The numerical results for secondary outcomes are also not reported in the information used. For safety, serious and other adverse-event counts are listed, but event terms for the other-event counts, death counts, and a comparative safety analysis are not reported in the registry record. These omissions limit interpretation of both efficacy outcomes and safety patterns.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients — NCT00838162.
• Registry record last updated 2013-06-12; status last verified 2013-06.
• Results first posted 2013-03-07.
• 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

NCT00838162 is a completed Phase IIa, randomized, open-label, parallel-group trial sponsored by Tibotec Pharmaceuticals, Ireland. It enrolled 33 treatment-naive participants with HIV-1 and evaluated four TMC310911 regimens coadministered with ritonavir for 14 days. The recorded start is 2009-06, and primary completion is recorded as 2009-08.

The primary outcome was mean change from baseline in plasma HIV-1 RNA, measured in log10 copies/mL at Baseline (Day 1), Day 8, and Day 15. The primary population was defined as participants who received at least 1 dose of TMC310911. The registry record does not report the numerical primary-outcome results, detailed statistical methods, or missing-data handling. It lists serious and other adverse-event counts for each regimen, but those counts do not provide a comparative safety analysis.