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 Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) (NCT04223791), a randomized phase 3 study. The primary outcome is Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04223791 |
| Phase | Phase 3 |
| Condition | HIV Infection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 643 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants had HIV-1 and were virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide before entering the study. The arm descriptions specify suppression for ≥3 consecutive months and no history of treatment failure. The primary analysis population consisted of participants who received ≥1 dose of study intervention, analyzed according to randomized group.
Intervention
The intervention was a switch to once-daily doravirine/islatravir, a fixed-dose combination of doravirine 100 mg and islatravir 0.75 mg. The study was designed to assess the switch in participants already receiving the comparator regimen.
Comparator
The active comparator was continued once-daily bictegravir/emtricitabine/tenofovir alafenamide. The study was randomized, double-blind, and parallel-group, so the treatment strategies were compared between assigned groups.
Primary question
At Week 48, was switching to doravirine/islatravir non-inferior to continuing bictegravir/emtricitabine/tenofovir alafenamide for the percentage of participants with HIV-1 RNA ≥50 copies/mL? The registry record describes this as the primary hypothesis. It does not report the group percentages, the between-group estimate, its confidence interval, or the non-inferiority margin, so the result of that test cannot be determined from the record.
3. Trial Design
This was a Phase 3, randomized, active-controlled, double-blind, parallel-group clinical study. It evaluated a treatment switch in participants with HIV-1 who were virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide. One group switched to once-daily doravirine/islatravir; the other continued the existing active regimen. The registry lists placebo interventions alongside the active drugs, consistent with the study’s double-blind description, but further details of the blinding procedures are not reported in the registry record.
The registry reports enrollment of 643. It lists the study as completed, with a start date of 2020-02-18 and a primary completion date of 2021-08-26. The primary endpoint was assessed at Week 48. Other listed outcomes include viral-load thresholds at Week 96 and Week 144, along with suppressed viral-load thresholds at those time points. The study summary also describes a 24-week extension for participants whose investigator determined they benefited from their assigned intervention. The adverse-event record includes open-label extension periods from Week 144 to Week 168 and post-treatment follow-up.
The primary outcome analysis population included participants who received ≥1 dose of study intervention, with participants analyzed in the group to which they were randomized. The registry does not report the number assigned to each group, the number contributing to the primary endpoint, or the number with missing Week 48 measurements. It also does not report the allocation ratio, details of sequence generation or concealment, or the planned sample-size justification. These design details should not be inferred from the overall enrollment or the study’s stated phase.
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.
Base Study (Day 1 to Week 144)
| Stage | DOR/ISL | BIC/FTC/TAF |
|---|---|---|
| STARTED | 322 | 321 |
| Treated | 322 | 319 |
| COMPLETED | 224 | 211 |
| NOT COMPLETED | 98 | 110 |
Reasons for not completing this period:
| Reason | DOR/ISL | BIC/FTC/TAF |
|---|---|---|
| Death | 2 | 0 |
| Lost to Follow-up | 5 | 8 |
| Physician Decision | 18 | 7 |
| Protocol Violation | 0 | 1 |
| Sponsor Decision | 11 | 39 |
| Withdrawal by Subject | 56 | 40 |
| Other | 6 | 15 |
Extension Study (Week 144 to Week 168)
| Stage | DOR/ISL | BIC/FTC/TAF |
|---|---|---|
| STARTED | 132 | 131 |
| COMPLETED | 10 | 2 |
| NOT COMPLETED | 122 | 129 |
Reasons for not completing this period:
| Reason | DOR/ISL | BIC/FTC/TAF |
|---|---|---|
| Lost to Follow-up | 1 | 1 |
| Physician Decision | 2 | 1 |
| Sponsor Decision | 91 | 124 |
| Withdrawal by Subject | 28 | 2 |
| Other | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis population consists of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
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 | DOR/ISL | BIC/FTC/TAF | Total |
|---|---|---|---|---|
| Participants analysed | 322 | 321 | 643 | |
| Age, Continuous | Years | 47.6 (SD 12.6) | 48.0 (SD 11.8) | 47.8 (SD 12.2) |
| Sex: Female, Male: Female | Participants | 105 | 78 | 183 |
| Sex: Female, Male: Male | Participants | 217 | 243 | 460 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 64 | 55 | 119 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 256 | 261 | 517 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 5 | 7 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 3 | 2 | 5 |
| Race (NIH/OMB): Asian | Participants | 14 | 13 | 27 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Black or African American | Participants | 59 | 56 | 115 |
| Race (NIH/OMB): White | Participants | 239 | 240 | 479 |
| Race (NIH/OMB): More than one race | Participants | 5 | 7 | 12 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 3 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48, measured over Week 48.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48. HIV-1 RNA is a measure of viral material in blood. The registry states that samples were assessed using the Abbott RealTime polymerase chain reaction assay, with a reliable lower limit of quantification of 40 copies/mL. The endpoint therefore focuses on whether a participant’s measured viral load met or exceeded the specified threshold at the specified follow-up time.
A threshold-based endpoint turns a continuous laboratory measurement into a binary outcome for each participant: the measurement is either at or above the threshold or it is not. The group percentage describes how common the defined outcome was in each assigned treatment group. The registry says these percentages were rounded to the nearest tenth digit and that the FDA Snapshot missing-data approach was used.
For a switch study, this endpoint addresses whether the proportion meeting the viral-load threshold after switching is acceptably comparable with the proportion under continued treatment. The registry states that the primary hypothesis was non-inferiority. In general, a non-inferiority conclusion depends on a prespecified margin and an estimate with appropriate uncertainty; the margin and the primary result are not reported in the registry record. The endpoint description alone cannot establish the study’s finding.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical question is whether the Week 48 percentage with HIV-1 RNA ≥50 copies/mL after switching to doravirine/islatravir was sufficiently similar to the percentage with continued bictegravir/emtricitabine/tenofovir alafenamide under the study’s non-inferiority criterion. The registry record identifies this question but does not give the group percentages or an estimate of their difference. It also does not report a confidence interval, p-value, or non-inferiority margin. Consequently, the primary comparison cannot be interpreted as meeting or failing the criterion from the record alone.
For a binary endpoint, each participant contributes an outcome classification under the specified threshold and time point. A group percentage expresses the observed frequency of that classification in the analysis population. The comparison is informative only when accompanied by uncertainty: a confidence interval indicates the range of effect estimates reasonably compatible with the data and the analysis assumptions. General statistical interpretation of a non-inferiority result requires assessing whether the interval excludes differences that exceed the prespecified margin in the unfavorable direction. The margin and interval are not reported in the registry record.
The registry identifies the primary analysis population as participants who received ≥1 dose of study intervention, analyzed according to randomized group. This approach retains the original assignment for those included, rather than reclassifying participants according to treatment actually taken. The outcome description also identifies FDA Snapshot as the missing-data approach. The specific missing-outcome classifications and the number of participants with unavailable Week 48 measurements are not reported in the registry record, so their influence on the percentage cannot be assessed from the information available.
There are listed viral-load outcomes at later follow-up, including Week 96 and Week 144, and outcomes using thresholds below 50 or 40 copies/mL. These are distinct outcome definitions or assessment times; they should not be treated as substitutes for the stated primary endpoint. The registry also lists 22 outcome measures and 17 analyses, but does not report a multiplicity strategy. Without the analysis plan and results, it is not possible to determine how the different outcomes relate to confirmatory testing or how any multiplicity was handled.
The serious adverse-event record gives counts by treatment period and group, with participants at risk indicated for each period. Those counts are descriptive and do not supply the primary efficacy comparison. They also do not, by themselves, establish a causal difference between treatments. Interpretation of safety requires attention to the period observed, the event definition, the relevant denominator, and uncertainty. The registry’s listed event terms and percentages should therefore be read as reported safety information, not as a substitute for a comparative safety analysis.
Overall, the record establishes the design, population focus, endpoint definition, and analysis approach for the primary outcome. It does not provide the numerical primary outcome results needed to judge the magnitude or precision of the treatment comparison. No conclusion about the non-inferiority hypothesis follows from the study title, completion status, or endpoint description alone.
9. Statistical Methods Explained
The study used a randomized, double-blind, parallel-group design with an active comparator. Randomization is intended, in general, to make assigned groups comparable on average with respect to factors measured and unmeasured before treatment assignment. It does not guarantee that every characteristic will be balanced in a particular study. The registry record does not report the randomization method, allocation concealment details, or group-specific baseline information.
What does the binary endpoint represent?
The primary outcome classifies participants using a viral-load threshold at Week 48. A binary endpoint records whether the defined condition is present or absent, rather than retaining the full numerical laboratory measurement as the outcome. The percentage with HIV-1 RNA ≥50 copies/mL is the frequency of participants meeting the endpoint definition in the analysis group. The assay’s reliable lower limit of quantification was 40 copies/mL. The endpoint threshold and assay limit serve different roles: one defines the outcome category, while the other describes the assay’s quantification capability.
Binary endpoints are often summarized with group percentages and a contrast between groups. A contrast may be expressed in several ways, but the registry record does not state the reported effect measure for this primary comparison. No group percentages or comparative estimate are reported in the record. Therefore, no numerical effect measure should be inferred from the endpoint description or enrollment.
How does non-inferiority differ from a test for any difference?
General explanation: a conventional superiority question asks whether evidence supports a difference in a particular direction. A non-inferiority question instead asks whether the intervention is not worse than the comparator by more than a prespecified amount, called the margin. This requires a clearly defined margin and an estimate sufficiently precise to rule out an unacceptable difference. A finding of non-inferiority does not mean that the treatments are identical. The registry names non-inferiority as the primary hypothesis, but the margin, statistical test, confidence level, and primary estimate are not reported in the registry record.
Because the endpoint is a percentage, the interpretation also depends on the direction and scale of the comparison. In general, a higher percentage meeting an adverse viral-load threshold would be less favorable for that endpoint. The exact contrast and decision rule used in the study cannot be reconstructed from the registry description. The sponsor’s primary analysis result is not reported in the registry record, so there is no sponsor result to compare with a recalculation.
What is a confidence interval for?
General explanation: an estimate from a study is subject to sampling variability. A confidence interval communicates uncertainty around an estimate under the statistical model and analysis assumptions. A narrow interval indicates greater precision than a wide interval, but it does not address every possible source of bias. For a non-inferiority analysis, the interval is assessed relative to the non-inferiority margin and the direction of the treatment contrast. Since neither the primary interval nor the margin is reported in the registry record, the precision and decision cannot be assessed.
How should the analysis population be understood?
The primary population is described as all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized. This is the stated population and assignment rule; it should not be relabeled as a full intention-to-treat analysis without further details. The registry does not report whether additional populations were analyzed for the primary non-inferiority question or how adherence, discontinuation, or protocol deviations were addressed.
What does FDA Snapshot indicate?
The registry says the primary measure uses the FDA Snapshot missing-data approach. General explanation: Snapshot methods define an outcome at a target time point using rules for measurements and participant status around that time, rather than simply treating every unavailable measurement as an observed laboratory result. The specific rules applied, including how missing measurements or treatment discontinuations were classified, are not reported in the registry record. The number of participants with missing Week 48 data and the impact of missingness on the result are also not reported.
Missing-data handling matters because the observed percentage can depend on which participants have an evaluable measurement and how unavailable outcomes are treated. A stated method improves clarity about the general approach, but a full assessment also needs the implementation details, participant flow, and sensitivity analyses. Those details are not reported in the registry record.
Why are there multiple outcome times and thresholds?
The registry lists secondary viral-load outcomes at Week 96 and Week 144, as well as thresholds below 50 or 40 copies/mL. These answer related but non-identical questions. Changing the time point changes the period over which the outcome is assessed, and changing the threshold changes the definition of the outcome. The registry also lists 22 outcome measures and 17 analyses. The multiplicity procedure, if any, and the hierarchy among outcomes are not reported in the registry record. General statistical principle: examining several outcomes can increase the chance of apparently notable findings arising by chance if the analyses are treated as independent confirmatory tests without an appropriate plan.
Finally, the record includes descriptive serious adverse-event information over several treatment and follow-up periods. General explanation: event counts and percentages describe observed safety experience, while comparative inference requires a defined contrast and uncertainty assessment. The registry’s period-specific figures do not supply such an inferential analysis. They should be interpreted within the stated follow-up periods rather than combined into an unreported overall comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary viral-load outcomes at Week 96 and Week 144, including thresholds below 50 and 40 copies/mL. It also reports 22 outcome measures and 17 analyses. The number of listed outcomes does not reveal which analyses were planned as confirmatory, whether hypotheses were ordered, or whether statistical error across analyses was controlled. A multiplicity strategy is not reported in the registry record.
The primary endpoint uses the FDA Snapshot missing-data approach. The analysis population consists of participants who received ≥1 dose of study intervention, analyzed in their randomized group. These details define the stated population and general missing-data approach, but do not describe all implementation choices. The rules for classifying unavailable Week 48 results, treatment discontinuations, or measurements outside the target visit are not reported in the registry record. Neither are the counts of participants with missing primary-outcome data or sensitivity analyses addressing missingness.
General explanation: missing outcome data can affect both the estimated group percentages and their uncertainty. A missing-data procedure makes assumptions about how unavailable information enters the analysis; those assumptions should be considered alongside the amount and pattern of missingness. In a non-inferiority study, sensitivity to analysis choices is particularly relevant because different assumptions can influence whether a conclusion meets the non-inferiority criterion. The registry record does not provide enough detail to evaluate this sensitivity.
The record states the primary analysis population but does not report additional analysis populations or whether results were checked under alternative population definitions. It also does not report the sample-size justification, interim analyses, or a detailed statistical analysis plan. These omissions limit assessment of the planned inferential framework; they do not establish that a particular method was or was not used.
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 |
|---|---|---|---|
| DOR/ISL: Base Study Week 0 - Week 48 | 14 | 322 | 4.3% |
| DOR/ISL: Base Study Week 48-Week 96 | 19 | 305 | 6.2% |
| DOR/ISL: Base Study Week 96-Week 144 | 7 | 266 | 2.6% |
| BIC/FTC/TAF: Base Study Week 0 - Week 48 | 16 | 319 | 5.0% |
| BIC/FTC/TAF: Base Study Week 48 - Week 96 | 11 | 301 | 3.7% |
| BIC/FTC/TAF: Base Study Week 96 - Week 144 | 6 | 281 | 2.1% |
| DOR/ISL: Open-Label Extension Week 144-Week 168 | 0 | 132 | 0.0% |
| BIC/FTC/TAF: Open-Label Extension Week 144 - Week 168 | 1 | 131 | 0.8% |
| DOR/ISL: Post-Treatment Follow-Up | 3 | 196 | 1.5% |
| BIC/FTC/TAF: Post-Treatment Follow-Up | 0 | 152 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DOR/ISL: Base Study Week 0 - Week 48 | 0 of 322 |
| DOR/ISL: Base Study Week 48-Week 96 | 2 of 305 |
| DOR/ISL: Base Study Week 96-Week 144 | 0 of 266 |
| BIC/FTC/TAF: Base Study Week 0 - Week 48 | 0 of 321 |
| BIC/FTC/TAF: Base Study Week 48 - Week 96 | 0 of 301 |
| BIC/FTC/TAF: Base Study Week 96 - Week 144 | 0 of 281 |
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 |
|---|---|
| DOR/ISL: Base Study Week 0 - Week 48 | 85 of 322 |
| DOR/ISL: Base Study Week 48-Week 96 | 104 of 305 |
| DOR/ISL: Base Study Week 96-Week 144 | 151 of 266 |
| BIC/FTC/TAF: Base Study Week 0 - Week 48 | 93 of 319 |
| BIC/FTC/TAF: Base Study Week 48 - Week 96 | 86 of 301 |
| BIC/FTC/TAF: Base Study Week 96 - Week 144 | 101 of 281 |
Most frequent serious adverse event terms
| Event term | Organ system | DOR/ISL: Base Study Week 0 - Week 48 | DOR/ISL: Base Study Week 48-Week 96 | DOR/ISL: Base Study Week 96-Week 144 | BIC/FTC/TAF: Base Study Week 0 - Week 48 | BIC/FTC/TAF: Base Study Week 48 - Week 96 | BIC/FTC/TAF: Base Study Week 96 - Week 144 |
|---|---|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | 2 of 322 | 1 of 305 | 1 of 266 | 0 of 319 | 0 of 301 | 0 of 281 |
| Colitis | Gastrointestinal disorders | 0 of 322 | 1 of 305 | 1 of 266 | 0 of 319 | 0 of 301 | 1 of 281 |
| COVID-19 | Infections and infestations | 1 of 322 | 1 of 305 | 0 of 266 | 0 of 319 | 0 of 301 | 1 of 281 |
| Atrial fibrillation | Cardiac disorders | 0 of 322 | 1 of 305 | 1 of 266 | 0 of 319 | 0 of 301 | 0 of 281 |
| COVID-19 pneumonia | Infections and infestations | 1 of 322 | 1 of 305 | 0 of 266 | 0 of 319 | 0 of 301 | 0 of 281 |
| Sepsis | Infections and infestations | 0 of 322 | 1 of 305 | 0 of 266 | 1 of 319 | 0 of 301 | 0 of 281 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 1 of 322 | 0 of 305 | 0 of 266 | 1 of 319 | 0 of 301 | 0 of 281 |
| Aortic valve incompetence | Cardiac disorders | 1 of 322 | 0 of 305 | 0 of 266 | 0 of 319 | 0 of 301 | 0 of 281 |
| Arteriospasm coronary | Cardiac disorders | 0 of 322 | 0 of 305 | 0 of 266 | 0 of 319 | 1 of 301 | 0 of 281 |
| Cardiac failure congestive | Cardiac disorders | 0 of 322 | 1 of 305 | 0 of 266 | 0 of 319 | 0 of 301 | 0 of 281 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DOR/ISL: Base Study Week 0 - Week 48 | DOR/ISL: Base Study Week 48-Week 96 | DOR/ISL: Base Study Week 96-Week 144 | BIC/FTC/TAF: Base Study Week 0 - Week 48 | BIC/FTC/TAF: Base Study Week 48 - Week 96 | BIC/FTC/TAF: Base Study Week 96 - Week 144 |
|---|---|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | 19 of 322 | 40 of 305 | 33 of 266 | 18 of 319 | 45 of 301 | 46 of 281 |
| Lymphocyte count decreased | Investigations | 1 of 322 | 32 of 305 | 86 of 266 | 0 of 319 | 8 of 301 | 28 of 281 |
| CD4 lymphocytes decreased | Investigations | 1 of 322 | 28 of 305 | 63 of 266 | 0 of 319 | 4 of 301 | 28 of 281 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 16 of 322 | 8 of 305 | 9 of 266 | 19 of 319 | 14 of 301 | 8 of 281 |
| Headache | Nervous system disorders | 26 of 322 | 14 of 305 | 3 of 266 | 22 of 319 | 6 of 301 | 1 of 281 |
| Back pain | Musculoskeletal and connective tissue disorders | 13 of 322 | 9 of 305 | 9 of 266 | 17 of 319 | 6 of 301 | 8 of 281 |
| Nasopharyngitis | Infections and infestations | 9 of 322 | 11 of 305 | 16 of 266 | 3 of 319 | 11 of 301 | 10 of 281 |
| Diarrhoea | Gastrointestinal disorders | 8 of 322 | 7 of 305 | 7 of 266 | 20 of 319 | 7 of 301 | 2 of 281 |
| Hypertension | Vascular disorders | 6 of 322 | 3 of 305 | 5 of 266 | 16 of 319 | 6 of 301 | 3 of 281 |
Serious events with the highest arm-level rate: vomiting (0.8%), acute myocardial infarction (0.6%), myocardial infarction (0.5%), osteoarthritis (0.5%), malignant melanoma (0.5%).
The registry reports serious adverse-event information separately by treatment period and group. For the DOR/ISL group, the Week 0 to Week 48 period lists 14 serious events among 322 participants at risk; for BIC/FTC/TAF over the same period, it lists 16 among 319 at risk. Later periods are separately recorded, including Week 48 to Week 96 and Week 96 to Week 144. The record also includes open-label extension and post-treatment follow-up periods. These are period-specific figures and should not be added together to create an overall count.
The registry lists serious-event terms that include vomiting at 0.8%, acute myocardial infarction at 0.6%, myocardial infarction at 0.5%, osteoarthritis at 0.5%, malignant melanoma at 0.5%, and atrial fibrillation at 0.4%. The record does not identify a denominator or group assignment for each listed percentage in the information available, so they should not be interpreted as group-specific rates.
Deaths are reported by period: the DOR/ISL group has 2 listed in the Week 48 to Week 96 period, with 0 in its other listed periods; the BIC/FTC/TAF group has 0 in each listed period. These descriptive entries do not establish that treatment caused or prevented an event. A full comparative safety interpretation would require definitions, exposure context, follow-up completeness, and estimates of uncertainty, which are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the trial was designed to compare a switch to doravirine/islatravir with continued bictegravir/emtricitabine/tenofovir alafenamide in participants with suppressed HIV-1. Its stated primary question concerns the percentage with HIV-1 RNA ≥50 copies/mL at Week 48 and is framed as a non-inferiority hypothesis. This identifies what investigators intended to test, not what the outcome demonstrated.
The primary group percentages, comparative estimate, confidence interval, p-value, and non-inferiority margin are not reported in the registry record. Without those quantities, it is not possible to assess the size of the observed difference, its precision, or whether the non-inferiority criterion was met. Completion status and enrollment do not answer that question. The listed endpoint and study design also cannot establish that the switch did or did not achieve a particular clinical outcome.
General explanation: a non-inferiority result, when supported by a prespecified margin and an adequately precise estimate, addresses whether an intervention is not unacceptably worse on the selected endpoint. It does not show that treatments are identical, nor does it establish equivalence across every outcome. Results for one endpoint and follow-up time do not automatically answer questions about later viral-load measures, other thresholds, safety, or outcomes beyond the observed study periods.
The safety entries describe serious adverse events in defined periods and list selected event terms. They are useful as descriptive registry information, but the entries alone do not establish comparative risk or causation. The record does not provide the comparative safety estimates and uncertainty needed to draw those conclusions.
Accordingly, the most defensible interpretation is limited to the study’s design and planned question. Numerical results needed to judge efficacy and comparative safety are not reported in the registry record. No treatment recommendation or conclusion about benefit follows from the information recorded.
13. Why This Trial Matters Statistically
This trial addresses a statistical question that commonly arises when evaluating a treatment switch: whether a new regimen can be compared with continued active therapy against a threshold-based outcome, while using a non-inferiority framework. The randomized, double-blind, parallel-group design and active comparator define a direct comparison between assigned strategies. The study also specifies the primary outcome threshold and follow-up time, making clear what the principal question concerns.
The endpoint illustrates how clinical interpretation depends on both outcome definition and analysis method. HIV-1 RNA is measured with a laboratory assay, while the primary analysis classifies participants using the ≥50 copies/mL threshold at Week 48. The record reports an assay quantification limit of 40 copies/mL and states that the outcome percentages were rounded to the nearest tenth digit. Understanding these distinctions helps prevent a threshold-based percentage from being mistaken for the full distribution of viral-load measurements.
The study also highlights why non-inferiority evidence requires more than a statement of the hypothesis. A decision depends on the prespecified margin, the treatment contrast, and its uncertainty. Those numerical results and details are not reported in the registry record. The absence of those data in the record limits what readers can conclude from the trial description, even though the design and endpoint are clearly identified.
Finally, later viral-load assessments and period-specific safety reporting show that outcome interpretation can vary by time point, threshold, and observation period. Those results need to be read according to their own definitions and analysis plans. The registry lists several outcomes but does not report the multiplicity strategy. This makes the record useful for identifying the study’s scope while also underscoring the importance of complete outcome and analysis reporting 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 most important limitation for interpretation is that the registry record does not report numerical results for the primary Week 48 outcome. Group percentages, the between-group estimate, its confidence interval, p-value, and non-inferiority margin are not reported. The primary hypothesis therefore cannot be evaluated from the record’s endpoint description.
Important design and analysis details are also absent. The registry does not report the group allocation counts, primary-outcome denominators, baseline viral-load summaries, participant flow, missing Week 48 counts, or the specific implementation rules for FDA Snapshot. It does not report the sample-size justification, allocation procedure, interim analyses, or detailed statistical analysis plan. The presence of a stated analysis population does not fill these gaps.
The registry lists multiple outcomes and analyses, but does not report the multiplicity strategy or identify how the secondary outcomes relate to the primary test. The statistical role of later time points and alternative viral-load thresholds therefore cannot be determined. Additional analysis populations and sensitivity analyses are not reported in the registry record.
Safety information is presented by treatment period, including serious-event counts, participants at risk, selected terms, and deaths. These entries do not provide an inferential comparison or enough detail to assess differences in exposure and follow-up across periods. The listed percentages for event terms have no denominator identified in the available record. They should not be interpreted as comparative rates.
These limitations concern what the registry record reports and what can be concluded from it. They do not show that omitted analyses were not conducted; their availability is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) — NCT04223791.
- Registry record last updated 2026-03-27; status last verified 2026-03.
- Results first posted 2022-08-22.
- 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
NCT04223791 is a completed Phase 3 randomized, double-blind, active-controlled, parallel-group study sponsored by Merck Sharp & Dohme LLC. It enrolled 643 participants and compared switching to once-daily doravirine/islatravir with continuing bictegravir/emtricitabine/tenofovir alafenamide in people with virologically suppressed HIV-1. The primary endpoint was the percentage with HIV-1 RNA ≥50 copies/mL at Week 48, analyzed in participants who received ≥1 dose and according to randomized group, using FDA Snapshot.
The registry describes non-inferiority as the primary hypothesis and lists later viral-load outcomes, extension periods, and period-specific safety information. It does not report the primary outcome values, comparative estimate, confidence interval, or non-inferiority margin. The record therefore defines the study question and some analysis features but does not provide enough numerical primary results to judge the stated hypothesis.