A Clinical Trial Comparing the Efficacy of Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus TDF/FTC/Efavirenz (TDF/FTC/EFV) in Patients With Undetectable Plasma HIV-1 RNA on Current First-line Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial Comparing the Efficacy of Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus TDF/FTC/Efavirenz (TDF/FTC/EFV) in Patients With Undetectable Plasma HIV-1 RNA on Current First-line Treatment (NCT01709084), a randomized phase 3 study. The primary outcome is Percentage of Participants With Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 400 Copies Per Milliliter (Copies/mL) at Week 48.

2. Clinical Question

3. Trial Design

This was a Phase 3b, randomized, open-label, parallel-group study, identified as SALIF in its official title. The registry lists an enrollment of 426. The two treatment groups were TDF/FTC/RPV and TDF/FTC/EFV; the posted primary outcome summaries list 213 participants in the first group and 211 in the second. Allocation was randomized, and masking was listed as none. The allocation method and any procedures used to conceal assignments are not reported in the registry record.

The trial was designed around non-inferiority in virologic response. Participants were already receiving first-line antiretroviral treatment with suppressed HIV-1 RNA. The study compared fixed-dose combinations, with the RPV combination taken with a meal and the EFV combination taken on an empty stomach at bedtime. Both regimens were continued until Week 48 according to the arm descriptions.

The registry lists the study as completed. The recorded start date is 2013-10-02, and the primary completion date is 2015-10-22. Janssen-Cilag International NV is listed as the sponsor. The registry record does not report the trial’s original sample-size calculation, the non-inferiority margin, or additional details about the randomization procedure. It also does not report whether outcome assessors or analysts were masked despite the open-label treatment assignment.

The primary outcome used a modified FDA Snapshot method in the intent-to-treat population. The registry record describes the population as randomized participants who took at least 1 dose of study drug. These details define the primary analysis population but do not, by themselves, explain how every form of missing or incomplete Week 48 data was classified.

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: The intent-to-treat (ITT) population included all participants who were randomized and who had taken at least 1 dose of study drug.

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 Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 400 Copies Per Milliliter (Copies/mL) at Week 48, measured over Week 48.

The primary endpoint was the percentage of participants with plasma HIV-1 RNA below 400 copies/mL at Week 48. It measures whether viral load remained below the threshold selected for the trial’s virologic-response outcome. The registry describes this endpoint as being obtained with the modified FDA Snapshot method, using the intent-to-treat population of randomized participants who had taken at least 1 dose of study drug.

A threshold-based endpoint turns a laboratory measurement into a binary response: each participant is classified according to whether the Week 48 viral-load result is below the stated threshold. Reporting the percentage makes the response frequency comparable between randomized groups. In general, binary endpoints are straightforward to interpret, but the percentage does not convey how far an individual’s measurement lies from the threshold or describe changes over time.

The trial’s objective was non-inferiority, not simply whether the two observed percentages were identical. To make that judgment, the difference between groups must be interpreted against a prespecified margin that defines the largest acceptable loss in response. That margin and the detailed decision rule are not reported in the registry record. The endpoint therefore identifies the clinical outcome being compared, while the posted arm percentages and their uncertainty do not alone show whether the formal non-inferiority criterion was satisfied.

7. Results Posted in the Registry

• TDF/FTC/EFV: 96.2% (203/211) versus 93.9% (200/213) on control; risk difference 2.3 percentage points (95% CI -1.8 to 6.4), risk ratio 1.02 (0.98–1.07); unadjusted two-proportion z-test p = 0.273.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Plasma HIV-1 RNA Levels < 50 Copies/mL at Week 48

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • TDF/FTC/EFV: 96.2% (203/211) versus 93.9% (200/213) on control; risk difference 2.3 percentage points (95% CI -1.8 to 6.4), risk ratio 1.02 (0.98–1.07); unadjusted two-proportion z-test p = 0.273.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between TDF/FTC/EFV and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Plasma HIV-1 RNA Levels More Than or Equal to (>=) 400 Copies/mL at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • TDF/FTC/EFV: 0.5% (1/205) versus 0.5% (1/201) on control; risk difference -0.0 percentage points (95% CI -1.4 to 1.4), risk ratio 0.98 (0.06–15.57); unadjusted two-proportion z-test p = 0.989.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between TDF/FTC/EFV and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Plasma HIV-1 RNA Levels >= 50 Copies Per Milliliter (Copies/mL) at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • TDF/FTC/EFV: 1.0% (2/205) versus 1.5% (3/201) on control; risk difference -0.5 percentage points (95% CI -2.7 to 1.6), risk ratio 0.65 (0.11–3.87); unadjusted two-proportion z-test p = 0.637.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between TDF/FTC/EFV and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary viral-load question by examining a lower suppression threshold, higher viral-load thresholds, treatment adherence, and treatment-emergent resistance mutations. Across the available viral-load summaries, the broad pattern is high percentages meeting suppression thresholds and low percentages meeting the specified higher-threshold outcomes. This is directionally consistent with the high response percentages in the primary outcome, but the endpoints do not have identical definitions or analysis methods.

Some secondary outcomes use the Time to Loss of Virologic Response method with non-virologic failure censored, whereas the primary endpoint is described as using a modified FDA Snapshot method. In general, outcomes based on different thresholds and imputation or censoring rules capture different aspects of response. They should be read as complementary summaries rather than combined into a single overall treatment effect.

The registry record does not report numeric results for treatment adherence based on tablet count or for treatment-emergent N[t]RTI or NNRTI mutations. Those outcomes therefore cannot be used to explain the observed primary percentages or to compare the regimens from the available record. Formal statistical analyses for the secondary outcomes are also not reported in the registry record.

Unadjusted secondary comparisons carry less weight than a prespecified primary analysis because several outcomes can create multiple opportunities for chance findings. The record does not report a multiplicity strategy, a hierarchy among secondary endpoints, or adjusted analyses. In general, secondary results can help describe consistency and generate questions, but an isolated unadjusted finding should not be treated as definitive evidence. The secondary endpoints provide context for the primary result; they do not resolve the missing non-inferiority margin or establish the trial’s formal primary conclusion.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Plasma HIV-1 RNA Levels < 50 Copies/mL at Week 48
• Percentage of Participants With Plasma HIV-1 RNA Levels More Than or Equal to (>=) 400 Copies/mL at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method.
• Percentage of Participants With Plasma HIV-1 RNA Levels >= 50 Copies Per Milliliter (Copies/mL) at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method.
• Percentage of Participant With Treatment Adherence Based on Tablet Count
• Number of Participants With Treatment-Emergent Nucleoside Reverse Transcriptase Inhibitor (N[t]RTI) or Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (NNRTI) Mutations

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: participants either had plasma HIV-1 RNA below 400 copies/mL at Week 48 or did not meet that threshold. The registry reports percentages by randomized group and a comparison expressed as a risk difference. A risk difference compares the response proportions by subtraction; its sign depends on the order in which groups are compared. In this comparison, the direction of the point estimate is consistent with the higher posted response percentage being in the TDF/FTC/EFV group. No new risk-difference value is calculated.

In general, a confidence interval describes a range of effect estimates compatible with the observed data under the statistical model and method used. For a difference, an interval that crosses zero includes no difference as one value compatible with the data. That does not establish that the groups are equivalent: the interval may also include differences in either direction. For a non-inferiority question, the relevant comparison is with the prespecified non-inferiority margin, not merely with zero. The margin is not reported in the registry record.

The unadjusted p-value for the primary comparison is 0.273. In general, a p-value summarizes how unusual the observed data, or more extreme data, would be under a specified null hypothesis and its assumptions. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result will replicate. The registry record does not describe a formal non-inferiority test or provide enough information to identify all statistical details behind the posted comparison. The p-value should therefore be read as an unadjusted comparison summary, not as the non-inferiority decision.

Relative measures such as a risk ratio compare the event or response frequencies as a ratio, while an odds ratio compares odds. These measures answer different questions from the risk difference and can be harder to interpret when the outcome is common. The posted primary response is high in both groups, making the absolute contrast especially useful for describing the observed separation. No adjusted effect estimate is reported in the registry record. A result should not be called adjusted unless the model and adjustment factors are specified.

The modified FDA Snapshot method is named for the primary endpoint, but the record does not give its detailed classification rules for missing or incomplete Week 48 observations. In general, an analysis method that classifies participants at a particular assessment can be affected by how missing measurements, treatment discontinuation, and other intercurrent events are handled. The stated intent-to-treat population also has a specific registry definition: randomized participants who took at least 1 dose of study drug. It should not be assumed to mean that every randomized participant contributed an observed Week 48 measurement.

The registry lists secondary binary outcomes using different viral-load thresholds and, for some outcomes, a Time to Loss of Virologic Response imputation method with non-virologic failure censored. In general, censoring means that certain observations do not count as the event of interest over the period after censoring. The record names this approach but does not provide detailed rules or a full account of how censoring was applied. This distinction matters because results from different definitions and analysis methods need not be directly interchangeable.

General statistical context: several outcomes can be tested or summarized in one trial. If many hypotheses are tested, the chance of at least one apparently notable result can rise unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity adjustment or a hierarchy for the secondary outcomes. The secondary summaries and unadjusted comparisons should consequently be treated as exploratory or descriptive unless a prespecified analysis plan establishes otherwise.

Some secondary outcomes are rare-event percentages. In general, estimates based on few events can be unstable, and relative measures can have wide uncertainty when event counts are small. The posted summaries include very low event percentages for the specified viral-load thresholds; they do not support a strong ranking of groups on those outcomes without careful attention to the reported uncertainty. The registry record does not list formal analyses for the secondary outcomes.

Finally, a statistical comparison is not a complete account of study conduct or clinical interpretation. Randomization supports comparison of assigned groups, but open-label assignment can affect behavior, adherence, reporting, or other aspects of care. Whether those pathways influenced these outcomes is not reported in the registry record. The posted summaries describe what was recorded under the stated design and methods, rather than resolving every possible source of uncertainty.

11. Confidence Intervals and Precision

The primary percentages are 93.9 for TDF/FTC/RPV and 96.2 for TDF/FTC/EFV. The comparison’s reported confidence interval extends from a negative to a positive value, including zero. Thus, the data do not pin down the direction of the difference with high precision: values consistent with a difference favoring either group remain within the interval. The interval should be interpreted alongside the point estimate, not as proof that the groups are identical.

In general, a confidence interval reflects both the estimated effect and the amount of uncertainty associated with it under the analysis method. A narrower interval indicates greater precision for the estimated effect, while a wider interval leaves a broader range of compatible effects. Precision is not the same as clinical importance. For a non-inferiority trial, the interval must be compared with the non-inferiority margin to determine whether effects judged unacceptably worse have been excluded. That margin is not reported in the registry record, so the interval cannot be used to verify the formal non-inferiority claim.

The unadjusted p-value of 0.273 is consistent with uncertainty about the contrast, but it does not summarize the size or clinical relevance of all effects compatible with the data. The registry’s arm percentages and comparison should be read as estimates from the observed study population under the stated endpoint method. They do not guarantee the same response percentages in another population or setting. Confidence intervals for the arm-specific percentages are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning entries are illustrations based on the observed effect, not the trial’s original design calculation. For these binary outcomes, the listed values are participants per arm, rather than total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for each scenario is the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the planning calculation associates with an 80% chance of detecting the specified effect under those assumptions, if that effect is the true one and the model assumptions hold. The 90% power column uses a higher target chance of detecting that effect, and therefore generally requires more participants per arm. These are design-planning quantities, not descriptions of the completed trial’s certainty.

Rows for planning for 100%, 75%, and 50% of the observed effect illustrate how the assumed effect size changes the required sample. Smaller effects are harder to distinguish from random variation and need more participants. The very low event rates in some secondary outcomes also make their planning illustrations especially sensitive to the observed event frequency; they should not be read as a recommended study size without a separately justified target effect and design.

This is not observed power. The calculations are planning illustrations from the observed effect under the listed assumptions, not a measure of the probability that the completed trial demonstrated its hypothesis. The registry record does not report the sample-size justification used when the trial was designed, so these illustrations cannot be taken as a reconstruction of that justification.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.939; treatment proportion p₁ = 0.962; average p̄ = 0.951.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3067 = 0.6011.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3062 = 0.2577.
4. n = (0.6011 + 0.2577)² / (0.0231)² = 1,380.1, rounded up to 1,381 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.938967136150235                          # control proportion
p1 <- 0.962085308056872                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1709084)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,381 (80% power), 1,848 (90% power)
 75% of observed effect: n per arm = 2,590 (80% power), 3,467 (90% power)
 50% of observed effect: n per arm = 6,132 (80% power), 8,209 (90% power)
power.prop.test: 1380.1 
Simulated power at n = 1,381 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and several secondary outcomes, but does not report a multiplicity plan. It does not say whether secondary hypotheses were adjusted for multiple comparisons, tested in a fixed sequence, or intended only for descriptive reporting. This matters because examining multiple outcomes can increase the chance of a seemingly notable result arising by chance. The available unadjusted comparisons should therefore be interpreted cautiously, especially for secondary outcomes.

The record does not report the prespecified non-inferiority margin, the formal statistical decision rule, or the complete primary analysis plan. Without the margin, the primary difference cannot be checked against the criterion that defines acceptable non-inferiority. The record also does not report whether a per-protocol analysis was performed or how any such result compared with the stated intent-to-treat analysis. Those details are important context for a non-inferiority objective.

The primary population is defined as randomized participants who took at least 1 dose of study drug, and the primary endpoint is described as using a modified FDA Snapshot method. However, the record does not report the detailed missing-data rules, the number of participants with missing Week 48 measurements, or the reasons measurements were unavailable. It does not report sensitivity analyses for alternative missing-data assumptions. For some secondary endpoints, a Time to Loss of Virologic Response method with non-virologic failure censored is named, but the full censoring and imputation rules are not reported in the registry record.

In general, missing-data methods can affect estimated response rates if the likelihood of missing results differs between groups or is related to outcome. Sensitivity analyses examine whether conclusions change under alternative assumptions. Their absence from the registry record means the robustness of the posted estimates to missing-data choices cannot be assessed from this record alone.

The registry lists no formal analyses for the secondary outcomes. That does not erase the posted arm summaries, but it limits what can be concluded about hypothesis testing beyond the primary comparison. The record also does not report interim-analysis procedures, stopping rules, or a complete statistical analysis plan.

15. Safety Results

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

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: diabetes mellitus (1.4%), hyperglycaemia (0.9%), abortion spontaneous (0.9%), anaemia (0.5%), neutropenia (0.5%).

The registry lists serious adverse events in 16 participants in the TDF/FTC/RPV group and 11 participants in the TDF/FTC/EFV group. The posted group summaries list other adverse events in 128 and 137 participants, respectively. These are counts, not comparative estimates adjusted for exposure duration or other factors. The registry record does not provide enough detail to interpret the counts as evidence that one regimen has a higher or lower overall risk.

Selected serious-event terms are listed with percentages: Diabetes Mellitus, 1.4%; Hyperglycaemia, 0.9%; Abortion Spontaneous, 0.9%; Anaemia, 0.5%; Neutropenia, 0.5%; and Gastrointestinal Inflammation, 0.5%. These terms describe reported events; the record does not provide a complete account of their severity, timing, relatedness, or distribution by treatment group. The listed terms should not be treated as mutually exclusive categories.

Deaths are not reported in the registry record. In general, safety counts are most informative when read alongside event definitions, follow-up duration, exposure, and a prespecified comparative analysis. Those details are not available in the posted summaries, so these figures are descriptive rather than a basis for a safety ranking.

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

The posted primary results describe high Week 48 response percentages in both randomized groups: 93.9 for TDF/FTC/RPV and 96.2 for TDF/FTC/EFV. The unadjusted comparison has a p-value of 0.273, and its confidence interval includes values on both sides of no difference. These summaries show that the observed response percentages were close, while leaving uncertainty about the direction and size of the underlying difference.

They do not establish that the treatments are equivalent or that either treatment is superior. They also do not, on their own, establish non-inferiority. That conclusion depends on a prespecified non-inferiority margin and analysis criteria, which are not reported in the registry record. A failure to demonstrate a difference in an unadjusted comparison is not proof that differences of meaningful size have been excluded.

The findings apply to the trial’s stated population and analysis definition: participants with suppressed HIV-1 RNA on first-line treatment, with the primary population defined as randomized participants who took at least 1 dose of study drug. They should not automatically be generalized to people with different treatment histories or clinical characteristics. Detailed eligibility criteria and results for adherence and treatment-emergent mutations are not reported in the registry record.

Likewise, the adverse-event counts provide descriptive safety information but do not establish a comparative safety profile. The registry record does not report deaths or enough analysis detail to assess whether differences in event counts reflect treatment, exposure, chance, or other factors. These statistics are an account of the posted trial results, not medical advice or a recommendation about treatment choices.

17. Why This Trial Matters Statistically

This trial illustrates an important distinction between a conventional difference question and a non-inferiority question. Similar observed percentages, or a non-significant test for difference, do not demonstrate non-inferiority. The non-inferiority margin is the benchmark that separates an acceptable loss in response from an unacceptable one; without the margin and its decision rule, the main design objective cannot be verified from the posted summary alone.

It also shows why an estimate and its uncertainty should be interpreted together. The arm percentages are high and close, but the confidence interval for the difference crosses zero. That interval permits uncertainty in either direction. A point estimate alone cannot show how much uncertainty remains, and a p-value alone does not establish that clinically important differences have been excluded.

The analysis population and endpoint definition matter as well. The registry describes a modified FDA Snapshot endpoint in participants who were randomized and took at least 1 dose. The secondary viral-load outcomes include different thresholds and a named censoring method. These choices define what each percentage represents and caution against treating all endpoint summaries as interchangeable.

Finally, the record demonstrates the limits of registry summaries for statistical appraisal. It lists the randomized design, arm results, and some safety counts, but does not report the original sample-size justification, multiplicity plan, full missing-data rules, or non-inferiority margin. Those omissions do not change the posted figures, but they limit the strength and specificity of conclusions that can be drawn from them.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the non-inferiority margin or full decision rule. This is a central limitation for interpreting a study whose stated objective is non-inferiority: the primary estimate and uncertainty cannot be judged against the threshold that defines an acceptable difference.

The record also does not give the original sample-size assumptions, detailed randomization procedures, or full statistical analysis plan. The sample-size illustrations based on the observed effect are not a substitute for the trial’s original design justification. The handling of missing Week 48 outcomes under the modified FDA Snapshot method is not described in sufficient detail to assess its impact, and sensitivity analyses are not reported.

Although several secondary outcomes are listed, formal analyses are not reported for them. The record does not describe a multiplicity strategy, so secondary comparisons have limited inferential weight. Numeric results for treatment adherence and emergent resistance mutations are not reported in the registry record, leaving those aspects of the secondary objectives unevaluated in the posted summaries.

The study was open-label, with masking listed as none. The record does not say whether outcome assessment or analysis was independently masked. The primary endpoint is a laboratory measure, but the posted record does not provide enough information to evaluate whether open-label conduct affected adherence, missing measurements, or other aspects of care. Detailed eligibility criteria are also not reported, limiting assessment of how well the enrolled population represents groups outside the stated suppressed first-line-treatment setting.

Safety information is limited to adverse-event counts and selected serious-event terms. Death counts and detailed event timing, relatedness, exposure-adjusted comparisons, and full group-specific term summaries are not reported in the registry record. These limits make the safety information descriptive rather than a complete comparative assessment.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Clinical Trial Comparing the Efficacy of Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus TDF/FTC/Efavirenz (TDF/FTC/EFV) in Patients With Undetectable Plasma HIV-1 RNA on Current First-line Treatment — NCT01709084.
• Registry record last updated 2021-02-11; status last verified 2021-01.
• Results first posted 2017-01-05.
• 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.

22. Record Summary

NCT01709084, titled SALIF in its official title, was a completed Phase 3b, randomized, open-label, parallel-group study sponsored by Janssen-Cilag International NV. It compared fixed-dose TDF/FTC/RPV with fixed-dose TDF/FTC/EFV in participants with suppressed HIV-1 RNA on first-line treatment. The registry lists enrollment of 426 and records the study start as 2013-10-02 and primary completion as 2015-10-22.

The primary endpoint was the percentage of participants with HIV-1 RNA below 400 copies/mL at Week 48, assessed with a modified FDA Snapshot method in the stated intent-to-treat population. The posted percentages were 93.9 and 96.2, respectively; the unadjusted p-value was 0.273, and the reported confidence interval for the group difference spans zero. The non-inferiority margin is not reported in the registry record, so the formal non-inferiority conclusion cannot be confirmed from these summaries.

Secondary viral-load outcomes and adverse-event counts are also listed. Detailed analyses, missing-data rules, and several design and safety details are not reported in the registry record.