A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care (NCT03227861), a na phase 3 study. The primary outcome is Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies/mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach.

2. Clinical Question

3. Trial Design

This is a Phase 3, single-arm, open-label study of a fixed-dose antiretroviral combination in newly diagnosed, treatment-naive participants with HIV-1. The registry lists no allocation to distinct arms and no masking. Enrollment was 109, and the study status is completed. The recorded study start was 2017-07-31, and primary completion was 2019-01-03.

Participants were to receive one oral tablet once daily containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg. The intervention description places the first dose within 24 hours of the screening or baseline visit. The study aimed to assess treatment in a Test and Treat model of care. The registry does not report a control regimen or a concurrent comparison group, so the design cannot directly estimate a treatment contrast against another regimen or usual care.

The primary endpoint is the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48, defined using the FDA Snapshot approach. The registry says that the approach uses viral load at the predefined time point within a time window together with study-drug discontinuation status. A participant with HIV RNA < 50 copies/mL at Week 48 is classified as a virologic success under that definition.

The registry lists 26 outcome measures, including viral-load and CD4+ cell-count outcomes at several follow-up times, as well as safety and treatment-discontinuation outcomes. It does not report the statistical analysis plan, sample-size justification, interim analyses, or a numerical result for the primary endpoint. Although the endpoint description names an intent-to-treat analysis set, the relationship between its reference to randomized participants and the listed single-group design is not explained in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Main Study Period (Week 0 to Week 48)

Reasons for not completing this period:

Extension Period (Week 48 to Week 96)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) analysis set included all the participants who were randomized and received at least one dose of study treatment in the study.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies/mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach, measured over Week 48.

The primary endpoint is a percentage: the proportion of participants classified as having virologic response at Week 48. The threshold is HIV-1 RNA < 50 copies/mL. The registry specifies the FDA Snapshot approach, which uses the viral-load measurement in the defined time window and also considers whether study treatment was discontinued. This makes the endpoint a classification at a particular follow-up time rather than a description of every viral-load measurement during the study.

A threshold-based endpoint is used to express whether participants meet a prespecified viral-load criterion at the stated time point. It is distinct from a continuous measure such as change in viral load, which is also listed among the secondary outcomes. The registry states that a participant with HIV RNA < 50 copies/mL at Week 48 is a virologic success under the Snapshot definition.

The record identifies the endpoint’s unit as percentage of participants and lists a 95% confidence interval as the measure of dispersion. However, neither the observed response percentage nor the numerical confidence interval is reported in the registry record. The endpoint’s definition is therefore available, but its estimated result and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry states the endpoint definition and the dispersion measure, but does not report a statistical analysis plan or a numerical primary result. The explanations below describe the statistical ideas relevant to the stated design and outcome; they do not infer methods that are absent from the registry record.

What does the primary endpoint count?

The primary outcome is a percentage of participants classified as responders at Week 48. The classification uses an HIV-1 RNA threshold of < 50 copies/mL and the FDA Snapshot approach. According to the registry, the approach considers the viral load at the predefined time point within a window and study-drug discontinuation status. That rule turns follow-up information into a responder or non-responder classification for the endpoint. The registry does not provide the resulting number of responders, the analysis denominator, or the percentage.

What does a confidence interval communicate?

General statistical explanation: a confidence interval expresses uncertainty around an estimate, given the data and method used. For a percentage, it gives a range of values compatible with the observed data under the interval procedure. It is not a guarantee that the true value lies in that particular interval, and it does not resolve limitations of the study design. The registry lists a 95% confidence interval for the primary endpoint but does not give its limits. The interval’s width, and therefore the reported precision, cannot be evaluated from the available record.

What can a single-group design establish?

General statistical explanation: a single-group study can describe outcomes observed among participants receiving the study intervention. It has no concurrent control group against which to estimate a randomized treatment difference. A response percentage in such a study does not, on its own, identify the cause of the observed outcomes. In this study, allocation is listed as not applicable and the model as single-group. The record does not identify an active or placebo comparison arm.

The absence of a control group also means that a between-arm contrast, such as a difference in response proportions, is not available. No effect estimate comparing treatment strategies is reported. Any interpretation should therefore stay with the study’s stated population, regimen, endpoint definition, and follow-up time rather than treating the observed outcome as a controlled comparison.

How should the Snapshot definition be understood?

The Snapshot approach is a rule for determining response status at a specified follow-up point. The registry says the rule uses viral load within a predefined time window and incorporates study-drug discontinuation status. This is important because endpoint classification is not simply a statement about the lab value in isolation: treatment discontinuation also enters the stated definition. The registry record does not describe further details of the window, handling of missing measurements, or the precise classification rules for every possible participant status.

General statistical explanation: a fixed-time binary endpoint can be easier to interpret as a proportion meeting a criterion, while it compresses a range of viral-load values and follow-up histories into a responder classification. Continuous viral-load changes, also listed as secondary outcomes, address a different question. Neither outcome type substitutes for the other, and the registry’s listed outcomes do not supply numerical findings.

What analysis details remain unknown?

The record identifies the primary endpoint’s population as an intent-to-treat set and describes that set as participants who were randomized and received at least one dose. It does not give the count analyzed, explain how this population definition is reconciled with the listed single-group design, or provide a statistical analysis plan. The record also does not report whether interim analyses were planned or performed, how the sample size was justified, or which exact procedure was used to calculate the confidence interval.

General statistical explanation: analysis populations matter because inclusion and exclusion rules determine which participants contribute to an estimate. Missing outcome data and treatment discontinuation can also affect how a binary endpoint is classified. Here the Snapshot description explicitly mentions treatment discontinuation, but detailed missing-data rules beyond that description are not reported in the registry record. No assumptions about those rules should be inferred.

The registry lists 26 outcome measures and identifies several secondary topics, but it does not report a multiplicity plan. General statistical explanation: when many outcomes or time points are tested, the chance of at least one apparently notable result can increase if the analyses are treated as independent opportunities without adjustment. A prespecified testing hierarchy or adjustment can address that issue, but neither is described in this record. The absence of a stated plan does not establish that no plan existed; it means the plan is not reported in the registry record.

The study details also include a planning-illustration assumption describing two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a fraction of an observed effect. Such assumptions are not evidence of the trial’s own design justification or of an observed-power calculation. The registry does not report a sample-size justification, and no numerical planning illustration is included in the registry record for this analysis. Any planning numbers should be understood as illustrations rather than observed findings.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("D/C/F/TAF: Main Study")
n      <- c(109)
events <- c(92)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  D/C/F/TAF: Main Study  109  92  84.4  76.2  90.6  76.4  90.0  76.4  90.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures, including several viral-load and CD4+ cell-count follow-up times, as well as discontinuation, adverse-event, laboratory, and resistance-related outcomes. It does not report a multiplicity strategy, such as a testing hierarchy or adjustment procedure. General statistical explanation: when several outcomes or time points are examined, the chance of finding at least one result that appears notable by chance may rise unless the analysis accounts for the number of comparisons. The record does not establish whether such a plan existed outside the registry entry.

The primary outcome is defined using the FDA Snapshot approach, which the registry says incorporates viral load within a predefined window and study-drug discontinuation status. However, additional rules for missing Week 48 measurements, incomplete follow-up, or other participant statuses are not reported in the registry record. The reported endpoint definition alone is not enough to reconstruct all participant classifications.

The stated primary analysis population is an intent-to-treat set of participants who were randomized and received at least one dose. The registry does not report the analyzed denominator or reconcile the reference to randomized participants with its single-group design and allocation listed as not applicable. The registry also does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. These omissions limit assessment of how the analysis was prespecified and how missingness and multiple outcomes were handled.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal injury (1.2%), muscle rupture (1.2%), cough (1.2%), meningitis aseptic (1.2%), head injury (1.2%).

The registry’s main-study safety summary lists 109 participants at risk for serious adverse events and 10 affected. It lists 109 at risk for other adverse events and 92 affected, with 0 deaths. For the extension study, it lists 80 participants at risk for serious adverse events and 4 affected, and 80 at risk for other adverse events and 45 affected, with 0 deaths. These are the recorded counts; no additional percentages should be inferred from them.

The registry lists serious adverse-event terms with percentages: Abdominal Injury, Muscle Rupture, Cough, Meningitis aseptic, and Head injury are each listed as 1.2%; Colitis is listed as 0.9%. These are the terms and values reported in the safety summary. The registry entries do not establish how the listed terms relate to each other at the participant level, or whether a participant could contribute more than one event.

The main-study and extension-study groups should not be added together or treated as a direct comparison. The relationship between participants across those study periods is not specified in the registry record, and the at-risk counts differ. These safety counts describe what the registry lists; they do not by themselves establish a causal relationship between treatment and an event.

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

The registry identifies a clear primary question: the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 under the FDA Snapshot definition. It also identifies the study as a completed Phase 3, open-label, single-group study of once-daily D/C/F/TAF, with enrollment of 109 participants. These registry entries describe the trial’s design and intended endpoint.

The record does not report the observed Week 48 response percentage or the numerical 95% confidence interval. It therefore does not provide the key result needed to quantify how many participants met the primary endpoint or how precise the estimate was. The endpoint definition is not a substitute for its numerical outcome.

Because there was no comparison group, the design does not furnish a randomized comparison with another treatment or care strategy. Even if a response percentage were reported, it would describe the study group under its endpoint rules and would not, by itself, establish a treatment effect relative to an alternative. The missing primary estimate further limits what can be said about the observed response in this registry record.

The safety summary reports affected-participant counts for serious and other adverse events in the main and extension study, along with listed serious-event terms and death counts. Those counts are descriptive. They do not, on their own, establish that the intervention caused or prevented any event, and the record does not provide a concurrent control group for comparison.

Accordingly, the record supports an account of the study design, regimen, endpoint definition, and posted safety counts. It does not support a numerical interpretation of primary efficacy, a treatment-versus-control effect, or conclusions about unreported analysis procedures. The statistical limitations arise both from the single-group design and from the absence of the primary outcome estimate and its interval.

14. Why This Trial Matters Statistically

This trial is statistically notable for pairing a clearly defined, fixed-time viral-load endpoint with a single-group design. The primary question is expressed as a percentage meeting the HIV-1 RNA threshold at Week 48, and the registry identifies the FDA Snapshot approach as the classification rule. That gives readers a defined outcome to interpret, while the absence of a control arm limits the kinds of treatment comparisons the design can make.

The distinction between an endpoint definition and an endpoint result is important. The registry states what counts as virologic response and names a 95% confidence interval as the dispersion measure, but it does not report the observed percentage or interval limits. Without those values, the response estimate and its precision cannot be evaluated from the registry record. Enrollment alone does not supply that missing information.

The record also illustrates why statistical interpretation depends on details beyond the outcome label. The Snapshot definition incorporates treatment discontinuation, while other missing-data rules and the analysis denominator are not reported. The intent-to-treat description refers to randomized participants even though the design is listed as single-group and allocation as not applicable. Those details leave questions about the analysis population unresolved.

Finally, the registry lists multiple outcome measures and safety summaries but does not report a multiplicity plan or detailed analysis plan. General statistical practice treats such details as relevant to judging how estimates and tests should be read. In this case, a careful account must distinguish the design and definitions that are recorded from results and methods that are not reported. That distinction prevents an endpoint description or safety count from being mistaken for a complete comparative efficacy analysis.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting the primary outcome is that its numerical result is not reported in the registry record. Although the endpoint is defined and a 95% confidence interval is named, neither the response estimate nor the interval limits are available. The record therefore does not permit assessment of the magnitude or precision of the primary endpoint.

The single-group design has no concurrent control arm. It cannot provide a randomized treatment contrast, and outcomes in the study group cannot by themselves distinguish treatment effects from other explanations. Allocation is listed as not applicable and masking as none.

The registry’s primary-population description refers to randomized participants who received at least one dose, while the study is listed as single-group. The record does not clarify this wording or state the primary analysis denominator. It also does not provide detailed rules for missing Week 48 measurements beyond the description that the Snapshot approach considers viral load and treatment discontinuation.

Further limitations in the available record include the absence of a statistical analysis plan, a sample-size justification, interim-analysis information, and a multiplicity plan. Although multiple outcome measures are listed, numerical findings for the primary endpoint and the listed secondary outcomes are not reported in the registry record for this analysis. The safety counts are descriptive, and their interpretation is limited by the absence of a comparison group and by the unspecified relationship between the main and extension study participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care — NCT03227861.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2020-01-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed Phase 3 study was open-label and single-group, with enrollment of 109 participants newly diagnosed with HIV-1 and antiretroviral treatment-naive. The intervention was once-daily oral D/C/F/TAF: darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg. The primary endpoint was the percentage with HIV-1 RNA < 50 copies/mL at Week 48 under the FDA Snapshot approach.

The registry record does not report the primary endpoint estimate or numerical confidence interval. It lists safety counts for the main and extension studies, but no control group is available for comparison. A detailed statistical analysis plan, sample-size justification, interim analyses, and multiplicity plan are not reported in the registry record.