Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection (NCT02384395), a na na study. The primary outcome is Number of Participants With Viral Load Measurement <200 Copies/mL at Week 24.

2. Clinical Question

3. Trial Design

NCT02384395 is a multicenter, single-arm, open-label study. The registry describes its purpose as examining the safety and virologic efficacy of a fixed dose combination of dolutegravir, abacavir, and lamivudine initiated during acute HIV infection. The study period is described as 96 weeks. The record lists planned enrollment of 40 participants, status as completed, a start date of 2015-09, and primary completion on 2020-03-06.

The intervention was the combination tablet containing dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg, taken orally once daily. There was no listed control arm. The allocation field is NA, the masking field is NONE, and the study model is SINGLE GROUP. Phase is listed as NA. As a result, this design can describe outcomes among participants receiving the regimen but does not provide a randomized, like-for-like treatment comparison.

The primary outcome was a count: the number of participants with an HIV-1 RNA measurement below 200 copies/mL at Week 24. Its description specifies that it concerns participants still on study at Week 24 and excludes 3 participants who terminated before that visit. The registry also lists three secondary outcomes: grade 3 or higher adverse events, the proportion of treated participants with HIV-1 RNA below 50 copies/mL at Week 48, and median change in HIV-1 RNA among participants completing the Week 24 visit.

Although the registry lists four outcome measures, it lists no analyses. A statistical analysis plan, details of any interim analyses, and a sample-size justification are not reported in the registry record. The available design information therefore supports a description of the study structure and stated outcomes, but not reconstruction of the planned analytical procedures or the rationale for the enrollment target.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Excludes 3 participants who terminated prior to Week 24

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 Number of Participants With Viral Load Measurement <200 Copies/mL at Week 24, measured over Week 24.

The primary endpoint is the number of participants with an HIV-1 RNA measurement below 200 copies/mL at Week 24. It is a count of participants meeting a threshold at a specified visit, rather than a continuous measure of viral load change. The endpoint description limits the population to participants on study at Week 24 and explicitly excludes 3 participants who terminated before that visit.

A threshold endpoint translates a laboratory measurement into a clearly defined outcome: whether an individual participant's measured value is below the stated cutoff at the assessment time. In general, such endpoints can make results easier to interpret as the number of participants reaching a prespecified state. They also discard information about how far measurements lie above or below the cutoff. A continuous outcome, such as change in viral load, addresses a different question and preserves information about magnitude of change.

The record does not report the number meeting the primary threshold, so the observed proportion or uncertainty around it cannot be described from the registered information. The 3 early terminations are excluded from the endpoint population as described; the record does not explain how missing Week 24 measurements among other participants, if any, were handled. The registry also does not report whether the cutoff was prespecified in a protocol or how the outcome was analyzed.

Interpretation should therefore stay close to the registered definition: a Week 24 count among participants still on study, using the stated threshold of less than 200 copies/mL. It should not be treated as a complete measure of change over time, nor as a comparative treatment effect, because this is a single-group study and the endpoint count is not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome type and estimand. The primary endpoint is a count of participants meeting a binary condition: HIV-1 RNA below 200 copies/mL at Week 24. In general, a binary outcome classifies each participant according to whether the condition is met. A count can then be reported for the defined population. The registry does not report that count, nor does it specify an accompanying estimate of uncertainty. The endpoint description defines the population as those on study at Week 24 and excludes 3 participants who terminated earlier. A fuller estimand would also specify how intercurrent events and unavailable measurements are treated; those details are not reported in the registry record.

What would a confidence interval describe?

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a proportion or treatment contrast. Its width depends on the data and the chosen method, and it does not remove limitations in the study design. For a single-group threshold outcome, an interval could describe uncertainty around the rate in the analyzed group if the numerator, denominator, and statistical method were reported. Here, the primary count is not posted, so no such interval can be interpreted from the registry information. A confidence interval would not create a randomized comparison where none exists.

Why does the single-group design matter?

In general, a concurrent control group helps distinguish changes associated with a treatment strategy from changes that might occur over time or for other reasons. Random allocation also helps balance measured and unmeasured characteristics across groups, on average. This trial is listed as SINGLE GROUP, with allocation NA and masking NONE; no control arm is listed. The design can describe outcomes and safety events in the treated group, but any before-and-after change would not, on its own, establish what would have happened to the same participants under an alternative treatment. The registry record does not report a comparative statistical analysis.

How should the safety counts be read?

The record reports serious adverse events for 37 participants at risk, with 5 affected, and other adverse events for 37 at risk, with 21 affected. It also lists 0 deaths. These are participant-level counts as recorded, not necessarily counts of distinct event episodes. The record does not clarify whether a participant could contribute to both event categories, nor does it provide the timing or duration of events. General safety interpretation distinguishes the number of participants affected from the total number of events; those quantities need not be the same. A percentage attached to an event term should also be read according to the registry's event reporting conventions, which are not described in detail.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variation in count data exceeds the variation assumed by a simple statistical model. If that feature is present, a model that assumes less variability can understate uncertainty and make estimates appear more precise than warranted. This is a general statistical concept; the registry record does not report a count model, a dispersion assessment, or an analysis requiring such an adjustment. The endpoint is a participant count, but the posted information does not establish that a model for counts was used.

What can be said about sample-size planning?

The record's planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of the observed effect. For time-to-event outcomes, its stated convention is a total number of events; for other outcomes, it is participants per arm. These are illustration assumptions, not a description of this single-group study's allocation. The record does not report a trial-specific sample-size justification, and the illustration is not observed power. Since no numerical planning outputs or observed primary result are reported in the registry information, no sample-size estimate or power conclusion can be drawn.

Finally, the registry lists four outcome measures and zero analyses. That means the available record gives outcome definitions but does not supply analysis specifications or numerical findings for the primary endpoint. The statistical plan, including any model, covariate adjustment, interim analysis, or multiplicity procedure, is not reported in the registry record. General statistical explanations should not be mistaken for methods documented as having been used in this study.

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("DTG/3TC/ABC FDC")
n      <- c(34)
events <- c(34)
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  DTG/3TC/ABC FDC  34  34  100.0  89.7  100.0  89.8  100.0  90.0  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary Week 24 count below 200 copies/mL and three secondary outcomes. The secondary outcomes concern grade 3 or higher adverse events, the proportion of treated participants with HIV-1 RNA below 50 copies/mL at Week 48, and median change in HIV-1 RNA among participants completing the Week 24 visit. The record lists zero analyses and does not report a statistical analysis plan or numerical results for these outcomes.

When several outcomes are examined, general statistical practice considers multiplicity because repeated testing can increase the chance of at least one apparently notable result by chance. Whether adjustment is appropriate depends on the aims and analysis plan. No multiplicity procedure, hierarchy among outcomes, or prespecified primary testing strategy beyond the named primary outcome is reported in the registry record. It is therefore not possible to determine whether any adjustment was planned or performed.

The primary endpoint description excludes 3 participants who terminated before Week 24. The handling of other missing measurements, if any, is not reported in the registry record. The record also does not specify whether an intention-to-treat, per-protocol, treated-participant, or other analysis population was used for the primary endpoint. The secondary Week 48 outcome is described as a proportion of treated participants, while the change outcome is described among participants completing the Week 24 visit; further rules for inclusion are not stated.

These reporting gaps limit assessment of bias from missing data and the comparability of populations across endpoints. No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record. The outcome definitions should therefore be distinguished from analysis procedures: the former are described, while the latter are not.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: exacerbation of asthma (2.7%), acute bronchitis (2.7%), abdominal pain (2.7%), diarrhea (2.7%), acute stress reaction (2.7%).

The registry reports serious adverse events for the DTG/3TC/ABC FDC group: 5 affected participants among 37 at risk. It separately reports other adverse events for 21 among 37 at risk and lists 0 deaths. These figures describe the recorded participants in each category. They do not by themselves establish that the intervention caused an event, or that the absence of a listed death demonstrates absence of risk.

The serious-event terms listed are Exacerbation of Asthma, Acute Bronchitis, Abdominal Pain, Diarrhea, Acute Stress Reaction, and Chest Pain associated with Back Pain. Each term is accompanied by 2.7%. The registry record does not provide further information on event timing, duration, recurrence, or attribution. The percentages should be read as recorded, without treating them as a direct comparison to another group; no such group is listed.

Participant counts and event-term listings are different kinds of safety information. A person may experience more than one event, and the record does not explain whether terms overlap or how event episodes were counted. These data are descriptive for a single treatment group, not a randomized comparison of safety outcomes. The record does not report additional detail needed to interpret risks by time on treatment or participant characteristics.

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

The registered information describes a completed, multicenter, open-label, single-group study of a fixed dose combination initiated during acute HIV infection. It states that the primary outcome was the number of participants with HIV-1 RNA below 200 copies/mL at Week 24, among those on study then, excluding 3 participants who terminated before that visit. It also reports selected safety counts. These registry entries describe the study and some posted safety information; they do not establish the primary virologic result because the count is not reported.

The study's single-group design matters when interpreting any observed outcomes. Without a randomized comparison arm, the study cannot directly estimate how outcomes would differ under another treatment or no treatment. An outcome in the treated group is descriptive; it is not, by itself, a causal treatment effect. This is a general limitation of uncontrolled comparisons, not a claim about the actual outcome of this study.

The absence of a posted primary count also means that the magnitude and precision of the primary outcome cannot be assessed. The record does not give a confidence interval, a test result, or a detailed analysis population. Nor does it report the secondary outcome values or analysis methods. The definitions can be described, but a conclusion about the frequency of Week 24 suppression or change in viral load cannot be reconstructed from the registry record.

The safety counts provide a limited descriptive snapshot. Serious adverse events were reported for 5 of 37 participants at risk, other adverse events for 21 of 37, and deaths were listed as 0. They should not be read as proof of cause, comparative safety, or a complete account of all possible harms. Additional details about event attribution and follow-up are not reported in the registry record.

Accordingly, the record supports an account of the design, treatment, stated endpoint, and some safety observations. It does not support claims that the regimen did or did not achieve a particular virologic outcome, nor a comparison with other treatments. Those conclusions require outcome and analysis information that is not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a clear statistical question: how to describe a threshold-based virologic outcome in a single group when the primary count is not posted. The endpoint is defined precisely enough to identify the threshold and visit, and it states that 3 early terminations are excluded. Yet without the count and denominator used in the analysis, readers cannot assess the observed rate or its precision. This illustrates why endpoint definitions and endpoint results are both needed for interpretation.

The study also shows why design information should accompany outcome summaries. A single-group, open-label study can document what was observed among its participants, but it has no randomized control arm for a direct treatment contrast. General statistical reasoning distinguishes description of outcomes from causal comparison; the design determines which kinds of claims the data can support.

Safety figures likewise need denominators and context. The registry reports 5 participants with serious adverse events among 37 at risk, 21 with other adverse events among 37, and 0 deaths. These counts are more interpretable than event terms alone, but they remain descriptive. The record does not provide enough detail to assess timing, attribution, or overlap between categories.

Finally, the record lists several outcomes but no analyses. The distinction between a stated outcome and an analyzed result is important: planned or registered endpoints do not reveal their observed values, and general methods cannot fill that gap. Statistical interpretation depends not only on the endpoint and design but also on transparent reporting of populations, missing-data handling, and estimates of uncertainty. Those elements are not reported in the registry record.

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 primary limitation for interpreting efficacy is that the registry defines the Week 24 endpoint but does not report its observed count. No estimate of precision or numerical primary result is available in the registry record. The stated exclusion of 3 participants who terminated before Week 24 also means the endpoint is not described for the full planned enrollment; the record does not explain how other unavailable measurements were handled.

The single-group, open-label design provides no randomized control comparison. It therefore cannot separate outcomes associated with receiving the combination from other influences. The record lists allocation as NA and masking as NONE, and no comparator is described. The phase is also listed as NA. These registry entries do not establish that the study lacked all procedural safeguards, but details beyond the registry description are not reported in the registry record.

The registry lists four outcome measures but zero analyses. Statistical methods, analysis populations, missing-data procedures, multiplicity handling, and any interim analyses are not reported in the registry record. The sample-size justification is also not reported. The planning illustration assumptions described for two-arm equal allocation do not match the listed single-group design and are not a substitute for a trial-specific justification.

Safety reporting is limited to participant counts, deaths, and selected serious-event terms with percentages. The record does not provide timing, duration, causal attribution detail, event recurrence, or whether participants could appear in multiple categories. Secondary outcome results are not reported. These limitations restrict assessment of efficacy, precision, missing-data bias, and the full safety profile from the registered information alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection — NCT02384395.
• Registry record last updated 2021-11-22; status last verified 2021-10.
• Results first posted 2021-11-22.
• 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.

19. Record Summary

NCT02384395 is a completed, multicenter, single-group, open-label study of dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg as a once-daily fixed dose combination initiated during acute HIV infection. Planned enrollment was 40; the study is described as 96 weeks. The registry lists a start date of 2015-09 and primary completion on 2020-03-06.

The primary outcome is the number of participants with HIV-1 RNA below 200 copies/mL at Week 24, excluding 3 participants who terminated before that visit. The count is not reported in the registry record. Safety information lists 5 of 37 participants at risk with serious adverse events, 21 of 37 with other adverse events, and 0 deaths. The registry lists four outcome measures and zero analyses; further statistical methods, missing-data handling, and a trial-specific sample-size justification are not reported.