Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284) (NCT02116660), a randomized phase 2 study. The primary outcome is Change From Baseline in Estimated Glomerular Filtration Rate (eGFR).

2. Clinical Question

The study addressed a switch in treatment among participants whose HIV-1 viremia was suppressed but whose renal function was impaired. The primary endpoint was renal function measured with eGFR, while the registry also lists outcomes concerning viral suppression, virologic failure, renal decline, resistance mutations, CD4+ T-lymphocyte count, liver enzymes, and lipid profile. These are outcomes of interest in the record, but the posted primary endpoint results concern eGFR change at week 48.

The comparison is between treatment strategies, not simply between individual drugs: the switch group received a three-drug combination, while the comparison group remained on tenofovir/emtricitabine with a ritonavir-boosted protease inhibitor. The study is described as a pilot study. Its small endpoint groups mean that the reported group means are best read as descriptive estimates, with substantial limits on precision and generalizability.

3. Trial Design

The registry describes a phase 2, randomized, parallel-group trial with no masking. It enrolled 11 participants and is listed as terminated. The start date was 2014-09-03 and the primary completion date was 2017-07-10. The sponsor is Merck Sharp & Dohme LLC. The official title identifies the study as the RANIA Study and a pilot study.

Participants were assigned to a switch regimen of raltegravir plus nevirapine and lamivudine or to a regimen of a ritonavir-boosted protease inhibitor plus tenofovir/emtricitabine. In the comparison group, the protease inhibitor options listed were lopinavir, atazanavir, or darunavir, each combined with ritonavir. The registry gives dosing schedules for the arm regimens. The listed duration for the switch medications was 96 weeks, while the primary renal endpoint was assessed at baseline and week 48.

Randomization can support a fair comparison by reducing systematic differences between groups, but it cannot guarantee that groups with very few participants will be similar in all characteristics. The record identifies the study as unmasked, so participants and study staff were not blinded to treatment assignment. Whether outcome assessors were masked is not reported in the registry record.

The primary endpoint population included randomized participants who received at least one dose of study medication and had both a baseline assessment and at least one post-baseline assessment. The arm results list 5 participants for raltegravir plus nevirapine plus lamivudine and 4 for the protease inhibitor/ritonavir plus tenofovir/emtricitabine group. Enrollment was 11. The registry record does not explain the difference between enrollment and the arm-specific primary endpoint counts, nor does it report the reason the study was terminated.

The record lists 19 outcome measures and 18 posted secondary outcomes, but no analyses are listed in the trial summary. Details of the randomization procedure, allocation concealment, protocol deviations, and the statistical plan are not reported in the registry record. Accordingly, design features that might affect interpretation beyond the stated randomization, masking, parallel model, and endpoint population cannot be assessed from this information.

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: All randomized participants who received at least one dose of study medications and who had both a baseline assessment, and at least one post-baseline assessment.

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 Change From Baseline in Estimated Glomerular Filtration Rate (eGFR), measured over Baseline and Week 48.

The primary endpoint is change from baseline in estimated glomerular filtration rate (eGFR), reported in mL/min, at week 48. eGFR is an estimate of how efficiently the kidneys filter blood. A change score expresses the week 48 measure relative to the participant’s baseline measure; a negative value indicates a lower measured eGFR than at baseline.

The registry states that eGFR was estimated with the Modification of Diet in Renal Disease (MDRD)-6 equation. The equation uses serum creatinine, age, sex, race, serum urea nitrogen concentration, and urine urea nitrogen excretion. Because eGFR is estimated from these inputs rather than measured directly, it is a derived clinical measure. Its use allows renal function to be represented on a continuous scale and compared over time.

For each arm, the posted result is a mean change with a standard deviation. The mean describes the average change among participants included in that arm’s endpoint analysis. The standard deviation describes how dispersed individual changes were around that group mean; it does not describe the precision of the mean itself. The registry gives the endpoint timeframe as baseline and week 48, so these results do not by themselves describe a longer-term trajectory or establish the durability of any change.

Using a renal measure as the primary endpoint fits the stated purpose of evaluating renal function after switching regimens in participants with impaired renal function. However, the posted arm summaries alone do not show the uncertainty around the difference between treatment groups, and the registry record does not report a formal between-group estimate or test for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a continuous endpoint such as change in eGFR, an arm mean summarizes the average observed change among the participants included in that arm’s analysis. It is a useful description of the center of the observed values, but it does not show whether most participants had changes close to the average. The standard deviation adds information about spread: a larger standard deviation means the observations are more dispersed around the mean. It is not a confidence interval and does not quantify the uncertainty in the treatment contrast.

What does a between-group estimate add?

A randomized trial’s central comparative question concerns the difference between treatment groups, rather than whether either group’s mean changed from baseline in isolation. A between-group estimate expresses the contrast in average outcomes under the two assigned strategies. Its confidence interval would describe a range of values compatible with the observed data under the analysis assumptions. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. The registry record does not report a between-group estimate or confidence interval for the primary endpoint.

A p-value, when reported, addresses how compatible the observed data are with a specified null hypothesis under a statistical model. It does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. No p-value or test result for the eGFR comparison is reported in the registry record. It would be inappropriate to infer one from the arm means and standard deviations or to treat a visual comparison as a formal test.

Why does the small group size matter?

Small samples tend to produce imprecise estimates. Even when randomization is used, chance imbalances in participant characteristics can occur, and observed averages can be strongly affected by a small number of individual values. The standard deviations reported for the two groups show variation in participant changes, but the small endpoint groups provide limited information about the range of plausible group-level effects. The registry summaries do not include individual participant data or a distributional plot description, so the shape of the outcome distribution cannot be assessed from the record alone.

More generally, normal-approximation methods for a mean or mean contrast rely on assumptions about the data and the sampling distribution. Their behavior can be difficult to assess in a very small sample, especially when observations are skewed or dominated by outliers. This is a general statistical consideration, not a claim about the distribution in this trial. The registry record does not describe a diagnostic assessment of the eGFR change distribution or any alternative analysis used if model assumptions were not met.

What role does randomization play?

Random allocation is intended to reduce systematic differences in prognosis between treatment groups. In a large study, randomization tends to balance measured and unmeasured factors over repeated assignments. In a small study, the particular assignment can still leave important factors unevenly distributed by chance. The registry identifies the allocation as randomized but does not report the sequence-generation method, concealment procedures, stratification factors, or baseline group characteristics. Those details are not reported in the registry record and cannot be assumed.

The study was unmasked. Lack of masking does not automatically invalidate an objective laboratory-derived endpoint, but knowledge of treatment assignment can influence behavior, co-interventions, follow-up, and outcome ascertainment in some settings. The registry record does not describe safeguards or whether the personnel calculating or assessing eGFR were unaware of assignment. Therefore, the possible influence of masking on conduct or measurement cannot be evaluated from the summary information.

How should change from baseline be understood?

A change score compares a follow-up measure with a baseline measure for the same participant, then summarizes those changes within a group. This can account descriptively for each participant’s starting value. A formal comparative analysis might instead model follow-up eGFR while accounting for baseline eGFR, or use another prespecified method. The statistical plan and exact method used to produce the posted means are not reported in the registry record. No adjustment for baseline values or other covariates should be presumed.

The endpoint definition specifies participants with a baseline assessment and at least one post-baseline assessment, while the endpoint timeframe is baseline and week 48. The registry record does not explain whether every participant in the summary had a week 48 value, how values at other follow-up times were used, or how missing endpoint measurements were handled. These details matter because analysis of only participants with observed follow-up can differ from an analysis that accounts for missingness under explicit assumptions.

How do planning illustrations differ from trial results?

A sample-size planning illustration uses assumptions about the effect to detect, allocation, significance level, and statistical approximation to show what a hypothetical design might require. Such an illustration is not an observed property of the participants and is not a measure of the probability that this trial detected an effect. The planning assumptions stated for the illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record explicitly distinguishes these illustrations from the trial’s own design. The trial’s sample-size justification is not reported in the registry record, and no planning illustration should be interpreted as observed power.

The registry identifies a continuous primary outcome and reports mean and standard deviation by arm, but it does not report a formal comparison, an analysis model, a confidence interval, or a test result. That absence limits inferential interpretation. The posted results are most defensibly read as descriptive endpoint summaries, with uncertainty emphasized rather than converted into a claim of equivalence, superiority, or a confirmed difference.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Raltegravir Plus Nevirapine Plus Lamivudine", "Protease Inhibitor/Ritonavir Plus Tenofovir/Emtric")
n   <- c(5, 4)
m   <- c(-1.1, -5.5)
sp  <- c(4.65, 11.78)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Raltegravir Plus Nevirapine Plus Lamivudine  5  -1.100  4.650  -6.874  4.674
CARM  Protease Inhibitor/Ritonavir Plus Tenofovir/Emtric  4  -5.500  11.780  -24.245  13.245

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and 18 posted secondary outcomes. Assessing multiple outcomes or time points creates a multiplicity issue: the more inferential tests conducted, the greater the opportunity for apparently notable findings to occur by chance when no true effect exists. Statistical plans may address multiplicity by prioritizing a primary endpoint, adjusting significance thresholds, or treating secondary outcomes as exploratory. The registry record does not report a multiplicity strategy, a hierarchy for testing outcomes, or which outcomes were intended to support confirmatory conclusions.

The primary outcome is change from baseline in eGFR at week 48. The record also lists secondary outcomes related to viral suppression at week 48 and week 96, renal decline, virologic failure, HIV-RNA values, resistance-associated mutations, CD4+ T-lymphocyte count, and altered liver enzymes and lipid profile. Listing an outcome does not mean that a result was posted or that it was formally tested. The statistical methods and results for outcomes not described in the posted primary summary are not reported in the registry record.

Missing data are especially relevant because enrollment was 11 and the endpoint arm counts were 5 and 4. The record does not explain the participant flow from enrollment to the primary endpoint population, provide reasons for missing observations, or state how missing values were handled. It also does not report sensitivity analyses or assumptions about participants without an observed week 48 outcome. The primary endpoint population definition requires baseline and at least one post-baseline assessment, but that definition alone does not explain the treatment of incomplete data.

The registry describes an analysis population based on treatment receipt and assessment availability. It does not provide a full intention-to-treat analysis description, a per-protocol definition, or details on exclusions and protocol deviations. These methods and populations are not reported in the registry record. Consequently, the extent to which the posted summaries retain the benefits of randomization or reflect selective availability of endpoint measurements cannot be determined from the summary information.

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: myocardial infarction (20.0%).

The safety summary lists serious adverse events among 6 participants at risk in the raltegravir plus nevirapine plus lamivudine group, with 0 affected, and among 5 participants at risk in the protease inhibitor/ritonavir plus tenofovir/emtricitabine group, with 1 affected. Deaths are listed as 0 in both groups. These counts are safety summaries and should not be treated as the primary endpoint analysis counts, which were 5 and 4 participants, respectively.

The record also lists myocardial infarction as a top serious adverse event term at 20.0%. It does not specify in this summary which group the term belongs to, the denominator used for that percentage, or further event details. The percentage should therefore be read only as a registry-listed summary, not as a rate that can be directly compared between groups.

With few participants at risk, event counts provide limited information about how often uncommon harms might occur in a broader population. The absence of recorded deaths or serious events in a group does not establish that the risk is absent. Conversely, an event recorded in a small group does not by itself establish that the treatment caused it. The registry record does not provide event narratives, exposure-adjusted rates, severity details beyond the serious-event classification, or a causal assessment for these figures.

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

The posted primary endpoint values describe average eGFR change from baseline to week 48 among the participants included in each arm’s endpoint summary. The raltegravir plus nevirapine plus lamivudine group had a mean change of -1.1 mL/min, with a standard deviation of 4.65 and 5 participants. The protease inhibitor/ritonavir plus tenofovir/emtricitabine group had a mean change of -5.5 mL/min, with a standard deviation of 11.78 and 4 participants. These summaries describe the observed groups; they are not a formal estimate of the difference between strategies.

Because no between-group confidence interval, p-value, or statistical test is reported, the precision of a comparative effect cannot be established from the registry record. The data do not support a claim that the treatment strategies were equivalent, nor do the means alone establish that one strategy caused a different renal outcome. A lack of a reported test is not evidence that no difference exists. It means the posted summary does not provide the inferential analysis needed to quantify that question.

The findings are limited to the endpoint population and follow-up represented by the posted values. Enrollment was 11, and the endpoint summaries include 5 and 4 participants. The registry does not explain the participant flow or missing outcomes, so it is unclear how representative these summaries are of all randomized participants. The small groups also leave the means vulnerable to individual observations and provide limited precision.

The registry status is terminated, but the reason is not reported in the registry record. Termination should not be taken as evidence for or against a treatment effect. The listed secondary outcomes may be relevant to the study’s broader aims, but the presence of outcome definitions is not equivalent to posted results or a completed statistical comparison.

In practical statistical terms, this is a small pilot study whose primary endpoint results are descriptive and uncertain. They can inform the characterization of the observed participants and identify questions for further study, but the record does not establish the size or reliability of a comparative effect. These results should not be extended to populations or treatment settings beyond those represented in this trial without additional evidence.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized design and a precise result are separate features. Randomization is an important way to reduce systematic allocation differences, but it cannot make a very small study automatically conclusive. With only 5 and 4 participants in the primary endpoint summaries, chance differences between groups and participant-level variability can have a strong influence on the reported means.

It also shows why reporting the endpoint definition and analysis population matters. eGFR is an estimated continuous measure, and the registry specifies its calculation basis and the requirement for baseline and post-baseline assessments. Yet the record does not explain the missing-data process, the exact analysis method, or a formal comparison between groups. Without those details, readers cannot determine how the observed means relate to the intended randomized comparison or how precisely a difference is estimated.

The trial’s stated pilot character is important context. Pilot results can describe feasibility or observed outcomes, but the registry record does not report its sample-size justification or a planned target for detecting a treatment difference. Planning illustrations based on the observed effect are not a substitute for a prospective design rationale and should not be interpreted as evidence of power in the completed study.

Finally, the listed safety counts demonstrate the need to separate event descriptions from causal conclusions. Small counts, a percentage without a stated denominator, and no event-level details leave substantial uncertainty. In combination, these features make transparent reporting of participant flow, analysis methods, uncertainty intervals, and adverse event context especially important for understanding a small clinical trial.

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 endpoint summaries involve very small groups: 5 participants in the raltegravir plus nevirapine plus lamivudine arm and 4 in the protease inhibitor/ritonavir plus tenofovir/emtricitabine arm. The standard deviations, 4.65 and 11.78, indicate variation in observed changes, but the registry does not report individual-level results or a confidence interval for the group contrast. The precision and stability of the means therefore cannot be assessed fully.

The record does not report why enrollment of 11 resulted in these endpoint counts, whether all included participants had an observed week 48 measurement, or how missing values and withdrawals were handled. The reason for the terminated status is also not reported in the registry record. Without these details, selection into the endpoint analysis and the completeness of follow-up remain unclear.

The trial was unmasked, and the registry does not describe outcome-assessment masking or other safeguards against influence of treatment knowledge. The randomization method, allocation concealment, baseline characteristics, adherence, concomitant care, and protocol deviations are not reported in the registry record. These factors can matter when interpreting a small randomized study.

No formal between-group analysis, test, confidence interval, or model description is reported for the primary endpoint. The record does not state a multiplicity plan for the many listed outcomes, a prespecified missing-data approach, or sensitivity analyses. It also does not give the rationale for the sample size. The listed serious adverse event percentage lacks a stated group and denominator in the summary, limiting interpretation. Together, these omissions constrain assessment of precision, bias, and generalizability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284) — NCT02116660.
• Registry record last updated 2019-04-08; status last verified 2019-04.
• Results first posted 2019-04-08.
• 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

NCT02116660 is a phase 2, randomized, open-label, parallel pilot study in participants with HIV-1, suppressed viremia, and impaired renal function. It compared switching to raltegravir plus nevirapine and lamivudine with a regimen of tenofovir/emtricitabine plus a ritonavir-boosted protease inhibitor. Enrollment was 11, and the registry status is terminated.

The primary endpoint was change from baseline in eGFR at week 48, estimated using the MDRD-6 equation. The arm mean changes were -1.1 mL/min (standard deviation 4.65; 5 participants) and -5.5 mL/min (standard deviation 11.78; 4 participants), respectively. The registry record does not report a formal between-group estimate, confidence interval, or test for this endpoint.

The record lists secondary outcomes and safety summaries, but details on the termination reason, missing data, statistical analysis plan, and sample-size justification are not reported in the registry record. The small endpoint groups and descriptive nature of the posted primary results limit conclusions about the comparative effect.