ART First-line Treatment Durability in Russia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ART First-line Treatment Durability in Russia (NCT04253119), a registered phase not stated study. The primary outcome is 48 Weeks Treatment Durability.

2. Clinical Question

The study addresses whether initial therapy was continued over follow-up in routine clinical practice, rather than comparing treatments under randomized assignment. Data were collected retrospectively from charts or medical records for patients who signed informed consent. The registry describes treatment-naive patients beginning ART and follow-up for up to 96 weeks, with information collected at baseline and around 48 and 96 weeks.

The registry record does not report the primary endpoint estimate, its 95% confidence interval, or results by regimen. It therefore does not answer the question with a numerical durability estimate. The endpoint definition focuses on whether the initial NNRTI or PI agent changed; it does not, by itself, describe every possible reason for a treatment change or establish why a person remained on or stopped a regimen.

3. Trial Design

This is a completed, non-interventional retrospective study of treatment-naive people with HIV-1 who initiated first-line ART in Russia. The registry lists an enrollment of 536. The study began on 2019-11-26, and primary completion was recorded as 2022-06-30.

According to the study description, information was obtained by retrospective review of charts or medical records from patients who signed informed consent. Treatment and diagnostic procedures followed each physician’s daily clinical practice; the study description says it required no study-specific procedures. The study was planned across 6 investigational sites, with up to 200 patients recruited per site. Those site-level figures describe the planned recruitment framework, not the number enrolled at each site.

Eligible treatment histories were described as initiation of an NNRTI plus two NRTIs or a PI boosted by ritonavir with two NRTIs. The listed NNRTIs were efavirenz, nevirapine, rilpivirine, and etravirine; the listed PIs were lopinavir, darunavir, atazanavir, and fosamprenavir. These are treatment categories in the study description, not evidence that every listed drug was used or that each regimen had a separate analysis.

Follow-up was retrospective for up to 96 weeks, with data collection at baseline and approximately 48 and 96 weeks after treatment began. The registry lists treatment durability at 48 weeks as the primary outcome, with 96-week durability and time on therapy at 48 and 96 weeks among the secondary outcomes. Allocation is not stated, and the registry does not describe randomized treatment assignment. It also notes that the arms are not a like-for-like control comparison. The methods used to identify sites and select records are not reported 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.

Before assignment: 536 subjects were enrolled instead of planned 1000 participants due to slow recruitment because of COVID-19 pandemia. This protocol deviation was documented accordingly.

Overall 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 48 Weeks Treatment Durability, measured over 48 weeks.

The primary endpoint is the percentage of participants who remained on their initial therapy without a change in the NNRTI or PI agent at 48 weeks. The registry specifies a percentage of participants as the measure and a 95% confidence interval as the dispersion measure. The endpoint is intended to describe treatment continuation in the study population over the specified follow-up period.

Durability is useful as a descriptive outcome because it captures whether a person stayed on the initial agent through follow-up. It is distinct from a direct measure of viral suppression, quality of life, or the clinical reason for continuing or changing therapy. A change in the NNRTI or PI agent is the event used in the stated endpoint definition; the registry does not specify how other regimen changes, interruptions, loss to follow-up, or death were handled in calculating it.

The registry record does not report the observed percentage or its confidence interval. Consequently, neither the level of observed durability nor the precision of its estimate can be assessed from the recorded results. The outcome title and definition establish what was intended to be measured, but do not establish the observed value.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on distinguishing the endpoint definition, the estimate, and the uncertainty around that estimate. The registry defines the primary endpoint as a percentage of participants remaining on initial therapy without a change in the NNRTI or PI agent at 48 weeks. It identifies a 95% confidence interval as the measure of dispersion. But the endpoint estimate and interval are not reported in the registry record, so there is no reported numerical result to interpret.

What does a percentage estimate represent?

For a binary endpoint, each participant is classified according to whether the defined event occurred within the stated assessment framework. A percentage describes the share classified in one category relative to the analysis population used for that calculation. The endpoint definition indicates continued initial therapy as the outcome of interest, but the registry does not report the analysis population, denominator, handling of missing outcome information, or the rules used to classify changes in therapy. Without those details and the estimate itself, the percentage cannot be reconstructed or checked.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimate under the statistical method used. A narrower interval indicates greater precision under that method; a wider interval indicates more uncertainty. The registry’s designation of a 95% confidence interval tells the reader the intended form of uncertainty reporting, not the width or location of the interval. Because neither the endpoint estimate nor its interval is reported, no conclusion about precision can be drawn.

How does the design affect statistical interpretation?

This study is retrospective and non-interventional. The treatment regimens were used in routine clinical practice, and the registry does not describe random assignment. In general, randomization can help balance measured and unmeasured characteristics between comparison groups. In an observational study, groups may differ in ways related to both treatment selection and outcome. Statistical adjustment can address some measured differences, but it cannot guarantee control of unmeasured differences. The registry record does not report an adjusted analysis, covariates, or a model, so no specific adjustment strategy can be attributed to this study.

The registry also warns that the arms are not a like-for-like control comparison. That caution matters: a comparison between groups, if made, would be descriptive unless the design and analysis supported a causal interpretation. The record does not report group-specific estimates or an analysis of treatment contrasts.

What can be said about planning assumptions?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the study’s original design or an observed-power calculation. The registry also says that time-to-event planning uses the total number of events, while other planning illustrations use participants per arm. The actual planning values are not reported in the registry record, and the record does not report the observed effect needed to interpret such illustrations. The planning assumptions do not establish that this observational study had two randomized arms or that equal allocation occurred.

Why does over-dispersion matter in general?

For binary data, a simple model may assume that observations vary according to a specified probability structure. If outcomes vary more than the model expects, uncertainty can be understated unless the analysis accounts for that extra variation. This is the general issue of over-dispersion. Whether it applies depends on the data structure and model. The registry record does not report a model, an over-dispersion assessment, or a method for addressing it; no claim about its presence or effect can be made for this study.

What analyses are documented?

The registry record lists no analyses. It identifies the primary and secondary outcomes but does not report statistical methods for estimating them, confidence-interval construction, model specifications, adjustment variables, subgroup analyses, or sensitivity analyses. The absence of those details limits independent assessment of how the listed outcomes would be calculated and how robust the findings would be to analytic choices.

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("Treatment-naive at the Time of Initiation of ART P")
n      <- c(536)
events <- c(407)
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  Treatment-naive at the Time of Initiation of ART P  536  407  75.9  72.1  79.5  72.1  79.4  72.1  79.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, 48-week treatment durability, and secondary outcomes covering 96-week durability and time on therapy at 48 and 96 weeks. It does not report how many hypotheses were formally tested, whether any outcome was designated for confirmatory inference, or how multiplicity was handled. In general, testing several outcomes or comparisons can increase the chance of at least one apparently notable result by chance. Methods such as adjustment or a prespecified testing hierarchy can address that issue, but no such plan is reported in the registry record.

The analysis populations are not described. The registry does not say whether analyses included all enrolled patients, only people with an available assessment, or another defined group. It does not report participant flow, completeness of follow-up, missing outcome counts, or how missing records were handled. These omissions matter because a percentage based only on participants with recorded follow-up can differ in meaning from one that accounts for everyone enrolled through an explicit method.

The endpoint is assessed at 48 weeks, while the study description refers to data collection at approximate time points. The registry does not explain the allowed assessment windows or how assessments outside those windows were treated. It also does not describe censoring or the treatment of death, discontinuation, or a regimen change for reasons other than the stated agent change.

No statistical analyses are listed in the registry record. As a result, methods for multiplicity, missing data, and population definition cannot be evaluated. These are unreported features, not evidence that a particular method was or was not used outside the registry record.

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.

The registry lists one group described as treatment-naive at the time of ART initiation per usual standard of care. For that group, the record reports 536 at risk for serious adverse events and zero serious events; it also reports 536 at risk for other adverse events and zero other events. The death count is zero. These are the counts recorded in the registry, not estimates of the probability of an adverse event.

A zero event count should be read cautiously. It does not establish that risk is absent, nor does it explain whether events were actively sought, how events were defined, how long safety follow-up lasted, or whether reporting was complete. Those details are not reported in the registry record. The study description emphasizes retrospective chart or medical-record review, which is relevant context for interpreting recorded safety information.

The registry does not give event terms for serious events, and it does not provide a narrative explaining the zero counts. The counts therefore support only a narrow statement about what was entered in the record. They do not permit comparison of safety between regimens or a broader conclusion about treatment safety.

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

The record establishes that a completed retrospective, non-interventional study examined treatment durability among treatment-naive people with HIV-1 beginning first-line ART in Russia. It defines the primary outcome as the percentage remaining on initial therapy without changing the NNRTI or PI agent at 48 weeks and specifies a 95% confidence interval as the intended measure of uncertainty. These details clarify the study question and the type of result that would answer it.

The record does not report the primary percentage, its confidence interval, or numerical results for the secondary outcomes. It therefore does not show how often participants remained on their initial therapy, how precisely that quantity was estimated, or whether outcomes differed by regimen. Nor does it provide an estimate of treatment effect relative to a comparator.

Because treatment was not described as randomized and the registry cautions that arms are not like-for-like controls, the study should not be read as establishing that one regimen caused greater durability than another. Observed continuation in routine care can reflect multiple influences, and the registry does not report reasons for changes or an adjusted comparative analysis.

The posted safety counts record zero serious adverse events, zero other adverse events, and zero deaths in the group described. Those entries do not establish that no adverse events occurred in all relevant records, or that the regimens have no risks. The registry does not detail how safety events were collected or adjudicated.

The most defensible conclusion is about the scope of the study rather than a treatment result: it was designed to describe durability in routine practice over follow-up, but the registry record does not present the outcome estimates needed to quantify that durability. No clinical recommendation follows from the information recorded.

14. Why This Trial Matters Statistically

Retrospective studies of routine care can describe how treatment is maintained outside a tightly controlled intervention. Treatment durability is a practical outcome because it concerns whether the initial agent continues over follow-up. Its interpretation nevertheless depends on a clear endpoint definition, reliable follow-up, and transparent reporting of changes and missing observations.

This study’s design makes the distinction between description and comparison especially important. The registry describes usual-care treatment and does not report random assignment; it also cautions that arms are not a like-for-like control comparison. That framing helps prevent a descriptive pattern from being mistaken for evidence that one regimen caused a better outcome. The design can still address a real-world question, but causal claims require support beyond a simple contrast between groups.

The registry record also illustrates why outcome definitions alone are not enough for statistical interpretation. A stated percentage endpoint and confidence-interval type tell readers what was intended to be measured, but without the estimate, interval, analysis population, and missing-data approach, the evidential result cannot be assessed. Reporting the estimate and its uncertainty is central to understanding both magnitude and precision.

Finally, the listed safety counts need their ascertainment context. Retrospective records can only support conclusions tied to what was documented and captured. Transparent descriptions of event definitions and follow-up would help readers judge what zero recorded events means. In this record, the study question is identifiable, but the numerical efficacy and detailed safety interpretation remain limited by unreported results and methods.

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 central limitation for interpreting this study from the registry record is that no numerical primary or secondary outcome results are reported. Although the primary endpoint and its intended confidence-interval format are defined, the estimate and interval are absent. The result’s magnitude and precision therefore cannot be assessed.

The retrospective chart-review design may depend on the completeness and consistency of clinical records. The registry does not report how records were selected, how treatment changes were verified, how outcome assessments were defined, or how incomplete follow-up was addressed. It also does not report reasons for changing therapy. These details would be needed to judge whether recorded treatment durability fully reflects the endpoint of interest.

The study is non-interventional, and allocation is not stated. The registry explicitly warns that the arms are not a like-for-like control comparison. Without reported group definitions, baseline characteristics, or adjusted analyses, treatment comparisons cannot be interpreted as causal. The record also does not state which factors were considered in any comparison.

The description gives follow-up for up to 96 weeks and approximate data-collection times, but does not report the analysis populations, assessment windows, participant flow, or missing-data methods. Multiplicity procedures, statistical models, and sensitivity analyses are also not reported. The registry lists zero adverse events and deaths, but does not describe safety-event ascertainment or completeness. These limitations restrict what can be concluded from the recorded information; they do not establish that unreported analyses or procedures were not conducted elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ART First-line Treatment Durability in Russia — NCT04253119.
• Registry record last updated 2024-04-17; status last verified 2024-04.
• Results first posted 2024-04-17.
• 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.

19. Record Summary

The registry record describes a completed retrospective, non-interventional study of first-line ART durability among treatment-naive people with HIV-1 in Russia. Enrollment is listed as 536. The study began on 2019-11-26, with primary completion on 2022-06-30. The primary endpoint is the percentage remaining on initial therapy without changing the NNRTI or PI agent at 48 weeks, with a 95% confidence interval specified.

The study description reports usual-care regimens and retrospective chart or medical-record review, with follow-up for up to 96 weeks. Secondary outcomes concern 96-week durability and time on therapy at 48 and 96 weeks. No outcome estimates, confidence intervals, or statistical analyses are reported in the registry record. Safety entries list zero serious adverse events, zero other adverse events, and zero deaths. Allocation, analysis populations, missing-data methods, and detailed safety ascertainment are not reported.