This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents (NCT00915655), a non-randomized phase 2 study. The primary outcome is Virological Response[Viral Load <50 Copies/mL, TLOVR].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00915655 |
| Phase | Phase 2 |
| Condition | HIV-1 Infection |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Tibotec Pharmaceuticals, Ireland |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled treatment-naive adolescents with HIV-1 infection aged 12 to <18 years and weighing at least 40 kg. Treatment-naive means the participants had not previously received treatment for HIV-1, as described in the registry summary. The registry record reports enrollment of 12 participants. The primary efficacy analysis population is identified as the ITT analysis set; further details about how that set was defined are not reported in the registry record.
Intervention
The intervention was darunavir with low-dose ritonavir once daily, taken with an investigator-selected background regimen of two nucleoside/nucleotide reverse transcriptase inhibitors. The listed background options were zidovudine/lamivudine or abacavir/lamivudine. The arm description specifies darunavir tablets 2 x 400 mg and ritonavir capsule 100 mg once daily for 48 weeks.
Comparator
There was no separate control arm. The design is recorded as single-group and non-randomized, so the study does not provide a randomized, like-for-like comparison between treatment strategies. The investigator-selected background regimens are components of the regimen, not comparator arms.
Primary question
The primary endpoint asks how many participants in the ITT analysis set met the specified virological-response definition at Week 24: confirmed plasma viral load <50 HIV-1 RNA copies/mL, assessed using the FDA Time to Loss of Virologic Response algorithm. The registry record does not report the response count or percentage, so the observed primary outcome cannot be described from this record.
3. Trial Design
This was a phase II, open-label clinical trial with a single treatment group. The registry lists allocation as non-randomized and masking as none. In practical terms, the record does not describe random assignment to different arms or masking of treatment assignment. All participants in the listed group received darunavir and ritonavir together with background antiretroviral therapy.
The intervention description specifies darunavir tablets 2 x 400 mg and ritonavir capsule 100 mg once daily for 48 weeks. Participants also received two nucleoside/nucleotide reverse transcriptase inhibitors selected by the investigator: zidovudine/lamivudine or abacavir/lamivudine. Because the background regimen could vary within the treatment group, the record describes a regimen strategy rather than a comparison of the two background options.
The study enrolled 12 participants and is recorded as completed. The registry gives a start date of 2009-07 and primary completion date of 2010-09. These record dates do not establish when each participant began or finished treatment, and individual follow-up details are not reported in the registry record.
The study was intended to evaluate pharmacokinetics, safety, tolerability, and antiviral activity in treatment-naive adolescents with HIV-1 infection. The primary efficacy endpoint was virological response at Week 24. The registry also lists virological response defined using viral load <50 copies/mL under FDA-SNAPSHOT as a secondary outcome. The results for either endpoint are not reported in the registry record.
Because the design has no randomized control group, observed changes cannot be interpreted as a controlled estimate of how the regimen compares with another treatment. The open-label, single-group structure can describe outcomes among enrolled participants, but it does not by itself separate treatment effects from other influences over time. The registry record does not report a protocol rationale for the design or a sample-size justification.
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
| Stage | DRV/Rtv |
|---|---|
| STARTED | 12 |
| COMPLETED | 12 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The ITT analysis set was considered the primary efficacy analysis set.
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.
| Characteristic | Unit | DRV/Rtv |
|---|---|---|
| Participants analysed | 12 | |
| Age Continuous | years | 14.7 (SD 1.69) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 4 |
| Percentile for Height | Height Percentile | 27.2 (0.5 to 94.1) |
| Percentile for BMI | BMI Percentile | 47.5 (13.3 to 85.9) |
| Percentile for Weight | Weight Percentile | 51.6 (8.6 to 79.0) |
6. Primary Endpoint
The registry lists the primary outcome as Virological Response[Viral Load <50 Copies/mL, TLOVR], measured over Week 24.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with virological response at Week 24. Response is defined as confirmed plasma viral load <50 HIV-1 RNA copies/mL and is assessed using the FDA Time to Loss of Virologic Response algorithm, abbreviated TLOVR. The record identifies the ITT analysis set as the primary efficacy analysis population.
This is a binary endpoint: each participant either meets the stated response definition or does not, according to the specified assessment. The response count can be expressed as a proportion or percentage, which gives a clinically interpretable summary of how many participants reached the threshold in the analyzed group. The registry’s endpoint description calls for a percentage, while the listed outcome unit is participants.
Using a prespecified viral-load threshold makes the outcome definition explicit. Requiring confirmed viral load below the threshold distinguishes the endpoint from a single, unconfirmed measurement. TLOVR is the named assessment algorithm, but its detailed rules for confirmation, follow-up, and handling of missing or changing measurements are not reported in the registry record. Those details matter because different rules can classify participants differently.
The registry record does not give the Week 24 response count, percentage, confidence interval, or other estimate. Therefore, the endpoint definition is available, but the observed magnitude and precision of the result are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies an endpoint and its assessment time, but does not report the primary endpoint result. No response count or percentage is available for the Week 24 TLOVR outcome. Accordingly, there is no posted effect estimate to interpret, and the result cannot be characterized as high, low, favorable, or unfavorable on the basis of this record.
The record also contains no analysis entries. It reports no confidence interval, p-value, or other inferential statistic for the primary endpoint. A confidence interval, in general, describes the statistical uncertainty around an estimate under the assumptions of the analysis. Without an estimate and its interval, the precision of the Week 24 response rate cannot be assessed. Without a reported hypothesis test, statistical significance cannot be evaluated. Neither omission establishes that an effect was absent; it means the relevant result is not reported in the registry record.
The study is a single-group, non-randomized trial. Any response observed among participants would describe outcomes under the regimen used in the study, not a randomized contrast with an alternative regimen. In general, a concurrent control group can help distinguish changes associated with treatment from changes that might occur for other reasons. This design does not provide that controlled comparison. The registry record itself flags that the arms are not a like-for-like control comparison; there is no separate comparator arm described.
Enrollment was 12. That is the recorded enrollment, not a reported count of participants with the primary outcome, and it should not be substituted for a Week 24 analysis denominator. The registry record does not report the number included in the ITT efficacy analysis, the number with outcome data at Week 24, or the handling of participants without a classifiable outcome. Thus, the amount of missing endpoint information and its possible influence on the response estimate are unknown from this record.
The secondary outcome is also a virological-response measure with the same viral-load threshold, described using FDA-SNAPSHOT. Its result is not reported in the registry record. No comparison of the primary TLOVR definition with the secondary SNAPSHOT definition can be made from the available outcome information.
The safety record lists serious adverse events and other adverse events for the DRV/Rtv group, but those counts do not supply the missing efficacy outcome. Safety counts are descriptive and should be read separately from virological response. Taken together, the record documents the trial design, endpoint definitions, enrollment, and selected safety information; it does not provide the primary efficacy result or its statistical uncertainty.
9. Statistical Methods Explained
The primary endpoint is binary because it classifies each participant according to whether the defined virological-response criterion was met at Week 24. For a binary outcome, a basic summary is the number meeting the criterion and the corresponding proportion among the analyzed participants. The registry record specifies a count-oriented unit and describes the endpoint in terms of a percentage, but it does not report the observed response count or percentage. Without those results, no response estimate can be interpreted.
What does a confidence interval add?
In general, a confidence interval presents a range of values compatible with an estimated effect under the statistical model and its assumptions. For a response proportion, it helps show how uncertain the estimate is, rather than presenting a point estimate alone. The width depends on such factors as the amount of outcome information and the method used to construct the interval. No confidence interval is reported for this primary outcome, and the record does not identify an interval method.
What does a p-value answer?
In general, a p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the test assumptions were true. It is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. The registry record reports no p-value or hypothesis test for the primary response endpoint. The null hypothesis and planned inferential approach are not reported in the registry record.
How should the design shape interpretation?
Randomization is a method for balancing, on average, measured and unmeasured participant characteristics across treatment groups. This trial is recorded as non-randomized and single-group, with no separate control arm. Consequently, the study can describe response observed in its treatment group but cannot estimate a randomized treatment contrast. A before-and-after interpretation, if outcome values were available, would also need to account for influences that change over time independently of treatment. No such comparative analysis is reported.
The open-label designation means the registry records no masking. In general, knowledge of treatment assignment can affect behavior, care, and the reporting or assessment of outcomes, depending on the outcome and trial procedures. A laboratory viral-load threshold is more objectively defined than a subjective outcome, but the registry record does not describe endpoint adjudication or safeguards against assessment bias. No further inference about the practical effect of open-label conduct is possible from the recorded design alone.
What does TLOVR specify?
The endpoint description names the FDA Time to Loss of Virologic Response algorithm and requires confirmed plasma viral load <50 HIV-1 RNA copies/mL at Week 24. The algorithm name indicates that response assessment is tied to virological response and its loss over time. The detailed operational rules are not reported in the registry record: for example, the record does not explain precisely how confirmation is determined, how observations at other visits contribute, or how missing measurements and treatment discontinuations are classified. Such rules can affect which participants count as responders, so a definition’s name alone is not enough to reproduce the analysis.
What is the role of the ITT set?
The registry identifies the ITT analysis set as the primary efficacy analysis population. In general, an intention-to-treat approach analyzes participants according to their assigned group, preserving the original comparison created by randomization. This study is not randomized and has one group, so the usual comparative rationale does not apply in the same way. The record does not define membership in the ITT set or say how participants with missing Week 24 results were handled. The label alone therefore does not reveal the analyzed denominator or the exact outcome rules.
For a binary endpoint, missing data can change a response proportion if participants without an observed outcome are excluded or classified by an analysis rule. General approaches include explicit missing-data assumptions and sensitivity analyses that examine how conclusions vary under alternative assumptions. The registry record does not report which approach, if any, was used. No missingness rate or sensitivity analysis is available.
What can be inferred from the statistical plan?
The record describes a planning illustration based on a stated fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. This is a planning framework, not a description of the actual trial design: the study itself is single-group and non-randomized. The assumptions do not establish that the trial was designed with two arms, and the planning illustration is not observed power. The registry record does not report the trial’s own sample-size justification or enough outcome information to assess a planning calculation.
More generally, over-dispersion matters when outcome variability is greater than assumed by a model: standard errors may then be understated and intervals too narrow if the extra variability is ignored. That concept is relevant to some statistical models, but the registry record does not identify an over-dispersion issue or a model for this binary endpoint. It would be inappropriate to infer that such a model was used.
Finally, the registry lists FDA-SNAPSHOT as a secondary response definition. Different analysis rules can yield different classifications, especially when outcomes are missing or follow-up differs. The record provides neither the secondary result nor the rules needed to compare its analysis with TLOVR. The statistical methods that were actually used beyond the named endpoint algorithm and ITT population are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary virological-response outcome and a secondary virological-response outcome. The primary outcome uses the TLOVR definition at Week 24; the secondary outcome is described as viral load <50 copies/mL under FDA-SNAPSHOT. The record does not report a multiplicity strategy, such as whether inference across outcomes was adjusted or whether the secondary outcome was intended to be descriptive. If multiple endpoints are tested, multiplicity can increase the chance of at least one apparently notable result by chance; adjustment and a prespecified testing hierarchy are general ways to address that issue. No such plan is reported in the registry record.
The primary efficacy analysis population is named as the ITT analysis set, but its exact definition and size are not reported. The registry does not state how participants with missing Week 24 measurements, treatment discontinuation, or other incomplete follow-up were classified under TLOVR. It also does not report the number with available endpoint data or a missing-data sensitivity analysis. These omissions prevent assessment of the outcome denominator and of how missingness may have affected the response estimate.
The registry record contains no analysis entries and no reported endpoint estimates, confidence intervals, or p-values. It does not describe interim analyses, a statistical analysis plan, or a sample-size justification. These details should be treated as not reported in the registry record, rather than assumed to have been absent from the conduct of the trial.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| DRV/Rtv | 3 | 12 | 25.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| DRV/Rtv | 11 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | DRV/Rtv |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 2 of 12 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 12 |
| Cervical dysplasia | Reproductive system and breast disorders | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DRV/Rtv |
|---|---|---|
| Nausea | Gastrointestinal disorders | 3 of 12 |
| Vomiting | Gastrointestinal disorders | 3 of 12 |
| Anaemia | Blood and lymphatic system disorders | 3 of 12 |
| Furuncle | Infections and infestations | 2 of 12 |
| Sinusitis | Infections and infestations | 2 of 12 |
| Diarrhoea | Gastrointestinal disorders | 2 of 12 |
| Pyrexia | General disorders | 2 of 12 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 12 |
| Asymptomatic bacteriuria | Infections and infestations | 1 of 12 |
| Bronchitis | Infections and infestations | 1 of 12 |
Serious events with the highest arm-level rate: anaemia (16.7%), neutropenia (8.3%), cervical dysplasia (8.3%).
For the DRV/Rtv group, the registry reports 12 participants at risk for serious adverse events and 3 participants affected. For other adverse events, it reports 12 at risk and 11 affected. These are participant counts in the registry’s safety summary; they are not counts of every individual event. A participant can experience more than one event, so participant counts should not be interpreted as total event counts.
The listed serious adverse-event terms are anaemia at 16.7%, neutropenia at 8.3%, and cervical dysplasia at 8.3%. These percentages are presented as recorded and should not be converted into event counts without the registry’s underlying event-level details. The record does not explain whether participants could appear under more than one term or provide enough detail to establish the timing, duration, severity grading, or relationship to treatment for these terms.
The deaths field is not populated in the record. Therefore, the death count is not reported in the registry record; a blank field should not be read as evidence that no deaths occurred. Serious and other adverse-event summaries describe safety observations in this study group, but they do not provide a randomized comparison or establish causation.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, open-label, single-group study evaluated once-daily darunavir with ritonavir and an investigator-selected background regimen in treatment-naive adolescents with HIV-1 infection. It describes the primary endpoint as confirmed plasma viral load <50 HIV-1 RNA copies/mL at Week 24 under TLOVR, with the ITT analysis set designated for primary efficacy. It also records enrollment of 12 and reports selected safety counts.
It does not report the Week 24 primary response count or percentage. The statistical uncertainty around that outcome is also unavailable: no confidence interval, p-value, or other primary effect estimate is reported in the registry record. As a result, the registry entry cannot establish how many participants met the endpoint, how precise that result was, or how it compared with a prespecified benchmark.
The design also limits what any observed response could mean. Because there is no separate randomized control group, a response observed in the treatment group would not by itself quantify a causal difference between this regimen and another strategy. The record provides no like-for-like control comparison. It also does not report the details needed to assess missing primary outcome data or reproduce the endpoint classification.
Safety observations are distinct from evidence about virological response. The adverse-event summary records affected participants and selected serious-event terms, but does not establish that the regimen caused those events. The death field is unpopulated, so deaths are not reported in the registry record rather than confirmed absent.
In short, the record supports a description of study design, intended endpoint, enrollment, and selected safety information. It does not support a conclusion about the observed primary efficacy result or comparative treatment effects. Those are limitations of the information recorded, not proof that a result was absent from other trial materials.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way its question and design differ. The registry describes a defined virological endpoint in a specific adolescent population, with a stated threshold, confirmation requirement, assessment time, and named TLOVR algorithm. Such details are important because a response estimate is only interpretable when the outcome definition is clear and consistently applied.
At the same time, a clearly stated endpoint is not a reported result. The registry gives no Week 24 response count, proportion, confidence interval, or p-value. This distinction is central to evidence interpretation: a study can document what it intended to measure without supplying the numerical outcome needed to assess magnitude or precision.
The single-group, non-randomized design also illustrates the difference between describing outcomes and estimating comparative effects. A treatment group’s outcomes may be informative about what was recorded during the study, but without a randomized comparator the design cannot provide the same basis for separating treatment effects from other changes or differences. The record explicitly indicates that the arms are not a like-for-like control comparison.
The registry’s identification of an ITT analysis set, alongside the absence of details about its membership and missing-data rules, highlights why analysis-population labels require supporting definitions. For a binary endpoint, the denominator and handling of unobserved outcomes are essential to interpreting a response proportion. Those details are not reported in the registry record.
Finally, the listed safety summaries and efficacy endpoint answer different questions and should not be conflated. Taken together, the entry is useful for identifying the design and planned measurement, while its unreported outcome results and analysis details limit 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 most direct limitation is that the primary Week 24 response result is not reported in the registry record. There is no count or percentage meeting the TLOVR definition, and no interval or test statistic with which to assess uncertainty. The listed secondary FDA-SNAPSHOT outcome also has no reported result.
The study is recorded as single-group, non-randomized, and open-label, with no separate control arm. It therefore does not provide a randomized comparison. The investigator selected one of the listed background regimens, but the record does not report how many participants received each option or provide a comparison between them.
The registry identifies the ITT set as the primary efficacy population but does not define it or report its analysis denominator. It does not report Week 24 outcome availability, missing-data handling, or sensitivity analyses. The details of the TLOVR implementation beyond the endpoint description are also not reported, limiting reproducibility.
Enrollment was 12, but the registry does not report a sample-size justification or explain the precision the study was intended to achieve. No interim-analysis plan, multiplicity procedure, or fuller statistical analysis plan is reported in the registry record. The sample-size assumptions described for a planning illustration should not be read as the trial’s own design rationale or as observed power.
For safety, the registry provides affected-participant counts and selected serious-event percentages, but limited detail about event timing, repeated events, treatment relationship, or the unpopulated deaths field. These constraints limit the conclusions that can be drawn from the registry entry; they do not establish what may or may not be available in other trial records.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Antiviral Activity of Darunavir + Ritonavir in HIV-1 Infected Adolescents — NCT00915655.
- Registry record last updated 2012-09-03; status last verified 2012-08.
- Results first posted 2011-12-28.
- 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.
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18. Record Summary
NCT00915655 is a completed phase II, open-label, single-group, non-randomized study of once-daily darunavir with ritonavir and investigator-selected background antiretroviral therapy in treatment-naive adolescents with HIV-1 infection aged 12 to <18 years and weighing at least 40 kg. Enrollment was 12. The regimen description specifies darunavir tablets 2 x 400 mg and ritonavir capsule 100 mg daily, with two NRTIs, for 48 weeks.
The primary endpoint was confirmed viral load <50 HIV-1 RNA copies/mL at Week 24 using TLOVR, with the ITT analysis set designated for primary efficacy. FDA-SNAPSHOT response was listed as a secondary outcome. Neither outcome result is reported in the registry record. The entry reports serious adverse events in 3 participants and other adverse events in 11 participants in the DRV/Rtv group; selected serious-event terms and percentages are also listed. No deaths count is reported.