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 The Late Presenter Treatment Optimisation Study (NCT03696160), a randomized phase 3 study. The primary outcome is Treatment Failure.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03696160 |
| Phase | Phase 3 |
| Condition | HIV/AIDS |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 447 |
| Arms in the primary outcome | n/a |
| Lead sponsor | NEAT ID Foundation |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with advanced HIV disease, described in the registry record as “late presenters.” The record does not give the detailed eligibility criteria or a more specific definition of advanced disease in the information available for this analysis. The registered condition is HIV/AIDS.
Intervention
Biktarvy is the integrase inhibitor combination evaluated in the study. Its listed components are bictegravir, emtricitabine and tenofovir alafenamide. The clinical question concerns its use as antiretroviral therapy in patients presenting with advanced HIV disease.
Comparator
Symtuza is the boosted protease inhibitor combination comparator. Its listed components are darunavir, cobicistat, emtricitabine and tenofovir alafenamide. The study compared the two treatment strategies in a randomised, parallel-group design.
Primary question
The primary question was whether treatment failure differed between the two regimens. Failure was a composite of virological and clinical reasons, including inadequate viral response or rebound, specified serious clinical events, clinically relevant adverse events, and immune reconstitution inflammatory syndrome requiring treatment. The registry record does not report a single numerical comparison or a statistical test for this outcome.
3. Trial Design
This was a Phase 3, randomised, open-label, multicentre, parallel-group study. The registry record lists an enrollment of 447 and describes the population as patients with advanced HIV disease, or “late presenters.” Participants were assigned to Biktarvy, an integrase inhibitor combination, or Symtuza, a boosted protease inhibitor combination. The record lists NEAT ID Foundation as the sponsor.
Because masking was listed as none, the study was open-label: treatment assignment was not masked in the registered design. Open-label conduct can matter when outcomes involve clinical judgement, decisions to change treatment, or reports of symptoms. The primary endpoint includes clinical events and adverse events, so knowledge of assigned therapy may be relevant when interpreting how those components were identified or recorded. The registry record does not describe procedures intended to reduce this risk.
The study start date is 2019-03-05, the primary completion date is 2024-06-17, and the status is completed. These are registry entries, not estimates of treatment effect. The listed primary-outcome timeframe is “Earliest at 12 weeks, latest 48 weeks.” The record also lists secondary outcomes involving viral load, CD4 measures, immune reconstitution inflammatory syndrome, infection-related hospitalisation or relapse, adverse events, and treatment changes.
Further design details—including the allocation ratio, randomisation procedure, site count, eligibility thresholds, and the intended sample-size justification—are not reported in the registry record. The record describes analyses using different patient numbers depending on whether the analysis is modified intention-to-treat (mITT) or per-protocol (PP), but does not supply the population definitions or outcome estimates for those analyses.
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: Number of Subjects Screened: 475
Overall Study
| Stage | Biktarvy | Symtuza |
|---|---|---|
| STARTED | 222 | 225 |
| COMPLETED | 220 | 222 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Biktarvy | Symtuza |
|---|---|---|
| Withdrew before IMP dosing | 2 | 3 |
Analysis population for the primary outcome, as defined in the registry: Each row represents a different analysis using different patient numbers, dependent on mITT or PP analysis
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 | Biktarvy | Symtuza | Total |
|---|---|---|---|---|
| Participants analysed | 220 | 222 | 442 | |
| Age, Continuous | Years | 44 (36 to 54) | 42 (34 to 51) | 43 (35 to 53) |
| Sex: Female, Male: Female | Participants | 40 | 44 | 84 |
| Sex: Female, Male: Male | Participants | 180 | 178 | 358 |
| Region of Enrollment: United Kingdom | Participants | 45 | 42 | 87 |
| Region of Enrollment: Spain | Participants | 61 | 61 | 122 |
| Region of Enrollment: France | Participants | 30 | 32 | 62 |
| Region of Enrollment: Belgium | Participants | 17 | 17 | 34 |
| Region of Enrollment: Italy | Participants | 28 | 30 | 58 |
| Region of Enrollment: Germany | Participants | 37 | 38 | 75 |
| Region of Enrollment: Ireland | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 43 | 40 | 83 |
| Race (NIH/OMB): White | Participants | 140 | 136 | 276 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 37 | 46 | 83 |
6. Primary Endpoint
The registry lists the primary outcome as Treatment Failure, measured over Earliest at 12 weeks, latest 48 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is treatment failure, counted as participants meeting a composite definition. The registry record includes both virological and clinical reasons for failure. Virological failure can mean an insufficient virological response or viral rebound. Clinical failure can include death related to HIV/AIDS or opportunistic infection, severe bacterial infection, a new or recurrent AIDS-defining event, a serious non-AIDS-defining event, clinically relevant adverse events of any grade, or immune reconstitution inflammatory syndrome requiring treatment.
A composite endpoint can capture several ways a treatment course may fail, rather than relying on a single event type. This can be useful when different clinically important events are relevant to the study question. However, components may differ in severity, frequency, and how readily they are assessed. A combined result, if reported, would not by itself show which component contributed most to the comparison. Component-specific results would be needed to understand that pattern.
The endpoint is expressed as a count of participants, and its timeframe is earliest at 12 weeks and latest at 48 weeks. The registry record says that each row represents a different analysis with different patient numbers, depending on mITT or PP analysis. It does not report a single consolidated primary-outcome estimate, the exact assessment schedule for this composite, or component-specific primary results. Accordingly, the endpoint definition can be described, but a treatment contrast cannot be interpreted from the registry record’s primary-outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomised comparison of Biktarvy and Symtuza in patients with advanced HIV disease. Randomisation is intended to make treatment groups comparable at the start of a trial, on average, but it does not replace examination of the outcome data. The record does not report a single primary-outcome estimate, confidence interval, or hypothesis-test result for treatment failure. It therefore does not establish the direction, size, or precision of a primary-outcome difference between the groups.
The primary endpoint combines virological and clinical events and can be assessed from earliest at 12 weeks to latest 48 weeks. A composite may summarize several relevant types of failure, but a composite contrast alone would not explain which component drove it. The record identifies analyses with different patient numbers depending on mITT or PP analysis, while the definitions of those populations and the corresponding estimates are not reported in the registry record. These omissions prevent a detailed assessment of which participants contributed to each analysis and how robust the endpoint results are across analysis populations.
The registry lists safety counts separately. For serious events, the Biktarvy group has 52 affected participants among 220 at risk, and the Symtuza group has 54 among 222 at risk. The record also lists other-event counts and deaths. These are descriptive safety figures; by themselves they do not establish whether treatment caused an event or whether an apparent difference is statistically reliable. No confidence intervals or comparative tests for these figures are reported in the registry record.
The list of serious-event terms includes immune reconstitution inflammatory syndrome at 2.3%, pneumonia at 1.8%, fever at 1.4%, cardiac arrest at 0.9%, cytomegalovirus infection at 0.9%, and IRIS associated Kaposi's sarcoma at 0.9%. These percentages describe the listed terms as recorded, but the registry information does not provide enough detail to determine their denominator or whether participants could contribute more than one term.
Thus, the posted information supports a description of the design, outcome definitions, and selected safety counts, not a conclusion about comparative effectiveness. The registry record does not report a statistical analysis plan, multiplicity approach, interim analyses, or the sponsor’s primary-outcome analysis. Those details are necessary for fuller interpretation and are not reported in the registry record.
9. Statistical Methods Explained
General statistical explanation: A randomised parallel-group study compares outcomes across groups assigned to different treatments. Random assignment is designed to limit systematic differences at baseline, though chance imbalances can remain. The analysis must still define which participants are included, how outcomes are measured, and how uncertainty around the comparison is quantified. The registry identifies this trial as randomised, parallel-group, and open-label, but the randomisation procedure and detailed analysis plan are not reported in the registry record.
What does a participant count represent?
The primary outcome is described as a count of participants who meet the treatment-failure definition. In general, a count communicates how many participants experienced the event under a stated analysis definition. It is not itself a complete comparison: interpretation also depends on the number of participants assessed, the follow-up period, and whether the same endpoint and analysis population were used in both groups. The registry record notes that the patient numbers differ by mITT or PP analysis, but does not report the corresponding primary-outcome counts or population-specific estimates.
For a binary outcome, a treatment comparison is often expressed as a difference or ratio between event risks, with a confidence interval. A confidence interval describes the range of effect sizes compatible with the data under the statistical model and indicates precision. It does not establish that an effect is clinically important, and a wide interval can leave substantial uncertainty even when a point estimate is available. No primary-outcome confidence interval or effect estimate is reported in the registry record, so this type of interpretation cannot be made for treatment failure.
Why does the composite definition matter?
General statistical explanation: Composite outcomes combine multiple event types into one endpoint. This may capture a broader picture of failure, but components can occur at different rates and have different clinical importance. A composite result can be influenced disproportionately by a more frequent component. Component-level summaries help clarify what the combined endpoint represents. In this study, the listed components span virological response, viral rebound, death and infection-related events, other clinical events, adverse events, and immune reconstitution inflammatory syndrome requiring treatment. Component-specific primary results are not reported in the registry record.
The endpoint’s timing also matters. The registry gives a timeframe from earliest at 12 weeks to latest 48 weeks, rather than a single uniform assessment time in the primary outcome description. In general, event definitions and assessment times should be prespecified and applied consistently. If follow-up duration differs, crude counts may not be directly comparable without an analysis that accounts for time at risk. The registry record does not report the detailed assessment schedule or a time-to-event analysis for the primary endpoint.
What do mITT and PP indicate?
General statistical explanation: An mITT analysis usually includes a defined subset of randomised participants, while a PP analysis generally focuses on participants who met specified protocol requirements. Exact definitions vary by trial and must be checked rather than assumed. These populations address different questions and can produce different estimates if exclusions or protocol deviations are related to outcomes. The registry says the primary outcome has different patient numbers depending on mITT or PP analysis, but the definitions, exclusions, and results for each analysis are not reported in the registry record.
Results across analysis populations are most informative when each population is clearly defined and the reasons for missing outcome data or exclusions are described. Without those details, it is not possible to assess whether the analyses preserve the benefits of randomisation or whether departures from the intended treatment strategy could affect interpretation. The registry record does not report missing-data handling or sensitivity analyses.
How should uncertainty and significance be read?
General statistical explanation: A hypothesis test evaluates data against a specified null model; its p-value does not measure the probability that a treatment works, nor does it describe the size or importance of an effect. Effect estimates and confidence intervals are needed alongside tests to assess magnitude and precision. The registry record reports no primary-outcome test or estimate, so there is no basis for describing statistical significance for that endpoint.
Multiplicity arises when several outcomes, time points, or analyses are tested. Repeated testing can increase the chance of at least one apparently unusual result unless the analysis plan accounts for it. This study lists multiple secondary outcomes and notes analyses using different patient numbers, but the method for handling multiplicity is not reported in the registry record. It also does not report whether interim analyses were conducted.
The registry includes a sample-size-assumptions description for planning illustrations: these are based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the stated fraction of the observed effect defines the target effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The trial’s own sample-size justification is not reported in the registry record. No planning values are included in the available record summary for interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a composite primary endpoint and multiple secondary outcomes, including viral load, CD4 measures, immune reconstitution inflammatory syndrome, infection-related outcomes, adverse events, and treatment changes. It also describes different analysis patient numbers according to mITT or PP populations. Testing several outcomes, time points, or populations can create multiplicity: in general, the more comparisons made, the greater the chance of a nominally unusual result arising by chance. A prespecified strategy can control or contextualize this issue, but the multiplicity approach is not reported in the registry record.
The primary outcome description states that each row represents a different analysis using different patient numbers, dependent on mITT or PP analysis. However, the population definitions and outcome estimates for those analyses are not reported in the registry record. The record also does not report an analysis hierarchy, which outcomes were confirmatory, or whether any interim analyses were planned or conducted.
Missing-data methods are not reported in the registry record. The record does not specify how participants with incomplete follow-up, unavailable endpoint assessments, or treatment discontinuation were handled in the primary analyses. Nor does it report sensitivity analyses examining the effect of missing outcomes. These details matter because the analysis population and treatment of missing observations can affect the estimated contrast and its precision. In their absence, the posted information does not allow a full assessment of multiplicity, missing-data risk, or the consistency of results across analysis populations.
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 |
|---|---|---|---|
| Biktarvy | 52 | 220 | 23.6% |
| Symtuza | 54 | 222 | 24.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Biktarvy | 9 of 220 |
| Symtuza | 3 of 222 |
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 |
|---|---|
| Biktarvy | 111 of 220 |
| Symtuza | 120 of 222 |
Most frequent serious adverse event terms
| Event term | Organ system | Biktarvy | Symtuza |
|---|---|---|---|
| Fever | General disorders | 3 of 220 | 3 of 222 |
| Immune reconstitution inflammatory syndrome | Immune system disorders | 5 of 220 | 1 of 222 |
| Pneumonia | Infections and infestations | 4 of 220 | 2 of 222 |
| Acute kidney injury | Renal and urinary disorders | 1 of 220 | 2 of 222 |
| Cytomegalovirus infection | Infections and infestations | 2 of 220 | 1 of 222 |
| Diarrhea | Gastrointestinal disorders | 1 of 220 | 2 of 222 |
| Acute renal failure | Renal and urinary disorders | 1 of 220 | 1 of 222 |
| Alcohol intoxication | Injury, poisoning and procedural complications | 1 of 220 | 1 of 222 |
| Cardiac arrest | Cardiac disorders | 2 of 220 | 0 of 222 |
| Clostridium difficile infection | Infections and infestations | 1 of 220 | 1 of 222 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Biktarvy | Symtuza |
|---|---|---|---|
| Headache | Nervous system disorders | 20 of 220 | 22 of 222 |
| Nausea | Gastrointestinal disorders | 16 of 220 | 21 of 222 |
| Cough | Respiratory, thoracic and mediastinal disorders | 15 of 220 | 16 of 222 |
| Insomnia | Psychiatric disorders | 16 of 220 | 15 of 222 |
| Rash | Skin and subcutaneous tissue disorders | 13 of 220 | 17 of 222 |
| COVID-19 | Infections and infestations | 13 of 220 | 15 of 222 |
| Diarrhoea | Gastrointestinal disorders | 11 of 220 | 17 of 222 |
| Fever | General disorders | 16 of 220 | 12 of 222 |
| Hypertension | Vascular disorders | 16 of 220 | 10 of 222 |
| Weight gain | Investigations | 13 of 220 | 10 of 222 |
Serious events with the highest arm-level rate: immune reconstitution inflammatory syndrome (2.3%), pneumonia (1.8%), fever (1.4%), cardiac arrest (0.9%), cytomegalovirus infection (0.9%).
The registry lists serious-event counts for participants at risk in each group. In the Biktarvy group, 52 participants were affected among 220 at risk; in the Symtuza group, 54 were affected among 222 at risk. The listed counts for other events are 111 among 220 at risk for Biktarvy and 120 among 222 at risk for Symtuza. Deaths are listed as 9 for Biktarvy and 3 for Symtuza. These are descriptive counts, not adjusted comparisons or evidence that treatment caused or prevented an event.
The serious-event terms listed include immune reconstitution inflammatory syndrome (2.3%), pneumonia (1.8%), fever (1.4%), cardiac arrest (0.9%), cytomegalovirus infection (0.9%), and IRIS associated Kaposi's sarcoma (0.9%). The registry record does not report the denominator for these percentages or explain whether a participant could appear under more than one term. The percentages therefore should be read as listed event summaries, not as a complete comparison between treatment groups.
In general, safety counts require context about follow-up duration, event definitions, severity, relatedness assessments, and missing data. Those details and comparative uncertainty estimates are not reported in the registry record. The counts alone do not establish a statistically reliable difference in safety.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomised, open-label, multicentre study compared Biktarvy with Symtuza in patients described as late presenters with advanced HIV disease. It also gives the definition and timeframe of a composite treatment-failure endpoint and reports selected safety counts. These details describe what the trial set out to compare and what safety events were recorded.
The posted information does not report a single primary-outcome comparison, an effect estimate, a confidence interval, or a statistical test. Consequently, it does not show whether treatment failure was more or less frequent in either group, or how precisely any such difference was estimated. The registry’s primary outcome description refers to different analyses with different patient numbers depending on mITT or PP analysis, but the associated results and population definitions are not reported in the registry record.
Even if a composite outcome estimate were available, it would need interpretation alongside its individual components. A combined endpoint can reflect multiple kinds of events, and a single summary cannot show which components contributed to the result. The registry record describes the components but does not provide their primary-outcome results separately.
The safety counts are also not proof of causation or a formal treatment comparison. Counts should be interpreted with attention to the number at risk, follow-up, event definitions, and uncertainty. The registry record does not report comparative confidence intervals or tests for the safety figures, nor does it give all the detail needed to interpret the listed serious-event percentages.
Accordingly, the record supports a description of trial design and selected registered outcomes, but not a conclusion that one regimen was superior, equivalent, or safer than the other. The primary statistical results and several methods needed to judge them are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial addresses a specific comparative question: whether an integrase inhibitor combination or a boosted protease inhibitor combination is associated with different outcomes among patients presenting with advanced HIV disease. The registry describes this as a population for whom the investigators sought to compare treatment approaches. The clinical focus makes the endpoint structure important: the primary outcome combines virological and clinical reasons for treatment failure rather than relying on a single type of event.
Statistically, the study illustrates why trial design and outcome reporting must be considered together. Randomisation supports a comparative design, while open-label conduct can be relevant when outcomes include clinical judgement or treatment decisions. A composite can capture a broad range of failures, but its interpretation depends on the event components and their individual contributions. Different mITT and PP analysis populations also make clear why population definitions and the handling of missing data are needed to interpret an estimate.
The registry includes a range of secondary outcomes and safety summaries, which can add context to the primary question. However, multiple outcomes and analyses require a clear statistical plan to distinguish confirmatory findings from exploratory ones and to address multiplicity. That plan is not reported in the registry record. Nor is a single primary-outcome effect estimate reported, so the available information cannot resolve the comparative question statistically.
The record is therefore useful for understanding the study’s design, endpoint choices, and the scope of registered outcomes. It also highlights the importance of complete result reporting: effect estimates, precision, analysis-population definitions, and missing-data methods are needed before readers can judge the strength and limits of evidence from a trial.
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.
Several trial-specific details needed for a full statistical appraisal are not reported in the registry record. The primary endpoint spans earliest at 12 weeks to latest 48 weeks, but the record does not give a single primary-outcome comparison or the assessment schedule that produced the analyses. It describes differing patient numbers for mITT and PP analyses without defining those populations or reporting their outcome estimates.
The study is open-label, and the primary composite includes clinical events and adverse events. The registry record does not describe whether outcome assessment was blinded, how clinical events were adjudicated, or what procedures were used to standardize assessment across centres. The definitions and classification procedures for the listed composite components are not detailed beyond the outcome description.
The registry record does not report the sample-size justification for the trial, the allocation ratio or randomisation procedure, the statistical analysis plan, or any interim analysis information. It also does not report methods for missing data, sensitivity analyses, or adjustment for multiple outcomes and analyses. These omissions restrict assessment of precision, robustness, and the intended interpretation of statistical tests.
Safety information is limited to counts and a list of serious-event terms with percentages. Comparative uncertainty estimates and details about follow-up, event relatedness, and the denominator for the listed percentages are not reported in the registry record. The record’s status is completed, but completion status alone does not supply the missing primary-outcome analysis or resolve these interpretive limitations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Late Presenter Treatment Optimisation Study — NCT03696160.
- Registry record last updated 2025-12-17; status last verified 2025-12.
- Results first posted 2025-12-17.
- 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
The Late Presenter Treatment Optimisation Study (NCT03696160) is a completed Phase 3, randomised, open-label, multicentre, parallel-group study sponsored by NEAT ID Foundation. It enrolled 447 participants with HIV/AIDS and compared Biktarvy, an integrase inhibitor combination, with Symtuza, a boosted protease inhibitor combination. The registered primary outcome is treatment failure, a composite of virological and clinical reasons, assessed earliest at 12 weeks and latest 48 weeks.
The registry also lists secondary outcomes concerning viral load, CD4 measures, immune reconstitution inflammatory syndrome, infection-related events, adverse events, and treatment changes. It reports selected serious-event counts, other-event counts, deaths, and serious-event terms. However, a single primary-outcome comparison, its effect estimate and precision, and the definitions and results for the mITT and PP analyses are not reported in the registry record. Key details about missing data, multiplicity, and the statistical analysis plan are also not reported in the registry record.