Safety of EVG+RTV Administered With Other Antiretroviral Agents for the Treatment of HIV-1 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of EVG+RTV Administered With Other Antiretroviral Agents for the Treatment of HIV-1 Infection (NCT00445146), a na phase 2 study. The primary outcome is Percentage of Participants Experiencing Any Treatment-Emergent Study Dug-Related Adverse Event.

2. Clinical Question

The clinical question is about long-term safety in a population already exposed to EVG+RTV in a prior study. It is not a randomized comparison of EVG+RTV against another treatment. The outcome focuses on whether a participant experienced at least one event meeting the endpoint’s treatment-emergent and study drug-related criteria. It does not, by itself, establish that the regimen caused an event.

The registry record describes the study objective as observing long-term safety when EVG boosted with RTV was used in combination with other antiretroviral agents. It does not report the primary endpoint result, so the percentage of participants meeting that endpoint cannot be stated from the record. The listed adverse-event summaries offer safety information, but they do not replace a reported primary endpoint result or establish a comparative treatment effect.

3. Trial Design

This was a phase 2, open-label, multicenter, single-group study of ritonavir-boosted GS-9137, also called EVG, combined with other antiretroviral agents. The registry record lists 192 enrolled participants. The study is marked completed, with its start recorded as 2007-02 and primary completion as 2015-03.

Participants had completed a prior EVG+RTV treatment study. The intervention was EVG with RTV and an antiretroviral regimen. The registry describes EVG 85 mg for participants receiving lopinavir/ritonavir or atazanavir/ritonavir as part of that regimen, and EVG 150 mg for other participants. It also says some participants may receive EVG 300 mg during the protocol. The registry record does not give further detail about the circumstances or timing of that dose change.

Open-label means the study was not masked. The record lists allocation as not applicable and the model as single group; it therefore does not describe randomized assignment to competing treatment arms. The listed treatment group is EVG+RTV, not a like-for-like control group. Any differences between participants or outcomes over time cannot be interpreted as a randomized contrast against another regimen.

The primary endpoint timeframe is up to Week 408 plus 30 days. The safety analysis set includes enrolled participants who received at least 1 dose of EVG. The registry record does not report a separate comparator, a randomization procedure, or a statistical analysis plan. It also does not report details of treatment exposure or follow-up by participant beyond the stated endpoint timeframe.

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: Participants must have been enrolled in other Gilead-sponsored studies of elvitegravir (EVG) + ritonavir (RTV) to be eligible to receive continued access to EVG+RTV in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: enrolled participants who received at least 1 dose of EVG

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.

Population: Safety Analysis Set: enrolled participants who received at least 1 dose of EVG

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Experiencing Any Treatment-Emergent Study Dug-Related Adverse Event, measured over Up to Week 408 plus 30 days.

The primary endpoint is the percentage of participants experiencing any treatment-emergent study drug-related adverse event, measured up to Week 408 plus 30 days. It is defined for the safety analysis set: enrolled participants who received at least 1 dose of EVG. The record does not report a numerical result for this endpoint.

This type of endpoint reduces each participant’s event experience to whether at least one event meeting the definition occurred. It is a binary outcome: a participant either meets the endpoint or does not. The percentage is intended to describe how common the defined event experience was in the observed safety population over the stated follow-up period. It does not convey the number of events per participant, their severity, or how long they lasted.

“Treatment-emergent” identifies events arising during the specified treatment or observation period according to the study’s endpoint definition. “Study drug-related” adds an assessment of relationship to the study drug. Such a classification is not, by itself, proof of causation. General statistical interpretation: an observed percentage is a description of the study population, while a confidence interval, if reported, would describe uncertainty around that estimate. The registry record does not report a confidence interval or the primary endpoint percentage.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines which statistical interpretations are appropriate. This is a single-group study, and the registry lists allocation as not applicable. There is no randomized control group in the record. A descriptive percentage can characterize the observed participants, but a comparison of treatment strategies requires a suitable comparator and a design that supports that comparison. General statistical explanation: randomization helps balance measured and unmeasured characteristics on average between assigned groups; without it, group differences may reflect factors other than treatment.

What does a participant-level percentage represent?

The primary endpoint is a binary participant-level outcome: whether a participant experienced any qualifying treatment-emergent study drug-related adverse event. A participant with multiple qualifying events still contributes as a participant who experienced the endpoint, rather than as multiple participants. General statistical explanation: a percentage for a binary outcome summarizes the share of the defined population meeting the outcome. It is not the same as an event rate per unit of time or a count of all events.

The endpoint applies to the safety analysis set, defined in the record as enrolled participants who received at least 1 dose of EVG. The stated timeframe is up to Week 408 plus 30 days. The record does not report a primary endpoint percentage, its numerator, its analysis denominator, or a confidence interval. Therefore, it is not possible to assess the observed endpoint frequency or its precision from the primary endpoint entry.

How should uncertainty be understood?

General statistical explanation: a confidence interval gives a range of values compatible with the data and the method used to calculate it. A narrow interval indicates greater precision than a wide interval, while neither width nor location establishes causality. For a participant-level percentage, uncertainty depends on the number of participants contributing usable outcome information and on the number meeting the endpoint. The registry record does not report a confidence interval for the primary endpoint, so no numerical statement about its precision is warranted.

The registry lists no analyses for the outcome record. That does not establish which analyses may have been conducted outside the registry; it means the registry record does not report them. No model, adjustment strategy, hypothesis test, or analysis specification for the primary endpoint is reported. Statistical methods such as adjusted regression, time-to-event analysis, or repeated-measures analysis should not be attributed to the study on the basis of the available record.

Why does the single-group design matter?

General statistical explanation: a single-group safety summary can describe events observed during the study, but it cannot isolate the contribution of a study drug from background illness, other treatments, or other influences. This matters in a study where EVG was used with an antiretroviral regimen and where the listed EVG dose could vary according to regimen or during the protocol. The record does not report analyses that separate outcomes by dose or concomitant regimen.

The planning illustrations associated with the posted results should be read as hypothetical planning calculations, not as observed power. Their stated assumptions use a two-arm, equal-allocation framework and an effect defined as a fraction of the observed effect. Those assumptions do not turn this single-group study into a randomized comparison. The registry record does not report a sample-size justification or a statistical design plan for this study. Planning calculations cannot fill in the missing primary endpoint result or establish that the study was powered for a particular safety question.

What is not reported about the analysis?

The registry record does not report an interim-analysis plan, a missing-data method, a prespecified multiplicity procedure, or a detailed statistical analysis plan. General statistical explanation: missing outcome data can affect a percentage if participants with unavailable information differ from those with observed information. The impact depends on the amount and pattern of missingness and on the handling method. Without those details, the direction or extent of any effect cannot be assessed. Likewise, when multiple outcomes or comparisons are examined, multiplicity procedures can affect how inferential results are interpreted; no such procedure is reported.

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("EVG+RTV")
n      <- c(192)
events <- c(28)
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  EVG+RTV  192  28  14.6  9.9  20.4  10.3  20.3  10.3  20.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures, including adverse-event and laboratory outcomes, but does not report a multiplicity procedure. It also does not report an analysis plan explaining which outcomes were treated as confirmatory or how results across outcomes were to be interpreted. General statistical explanation: examining multiple outcomes can increase the chance of finding an apparently notable result by chance if each is assessed separately. A prespecified multiplicity strategy can address that issue, but none is reported in the registry record.

Missing-data handling for the primary endpoint is not reported in the registry record. The safety analysis set is defined as enrolled participants who received at least 1 dose of EVG, but this definition alone does not explain how participants with incomplete follow-up or unavailable event information were handled. The record does not state whether follow-up time varied, whether participants discontinued, or how any such information was incorporated into the endpoint analysis.

General statistical explanation: if some participants have no usable endpoint information, the reported percentage and its precision can depend on how those participants are treated. The direction of any resulting bias cannot be determined without information about missingness and the analysis method. The record also does not report sensitivity analyses addressing missing outcomes.

The record does not describe further analysis populations beyond the safety analysis set definition given for the primary endpoint. It does not report exclusions, endpoint adjudication details, or a method for handling participants who began but did not complete follow-up. These omissions limit assessment of how fully the endpoint definition was applied and how representative the analyzed observations were of the enrolled group.

12. 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: pneumonia (4.7%), atrial fibrillation (2.6%), cellulitis (2.6%), acute kidney injury (2.6%), myocardial infarction (2.1%).

The registry safety summary lists 86 affected among 192 at risk for serious adverse events and 172 affected among 192 at risk for other adverse events. These are separate entries in the record. They should not be added together, treated as mutually exclusive participant groups, or read as counts for the primary endpoint. The record does not specify whether an individual could appear in both categories.

The primary endpoint is narrower in its wording: it concerns any treatment-emergent study drug-related adverse event. The serious and other adverse-event counts are not identified as results for that endpoint. In particular, the record does not report the number meeting the primary endpoint definition or the percentage for it.

The record lists serious adverse-event terms with percentages: pneumonia (4.7%), atrial fibrillation (2.6%), cellulitis (2.6%), acute kidney injury (2.6%), myocardial infarction (2.1%), and gastroenteritis (2.1%). These entries should be read as reported event-term summaries, not as comparisons between treatments. The registry record does not provide a comparator or enough detail to infer causation from these percentages. It also does not report a confidence interval for these term percentages.

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

The study addresses long-term safety observation among participants who had completed a prior EVG+RTV study and then received EVG+RTV with other antiretroviral agents. Its follow-up endpoint extended up to Week 408 plus 30 days. The registry record therefore describes a substantial planned observation horizon, but a long timeframe alone does not indicate what the primary endpoint result was.

The posted safety entries show that the registry records affected participants for serious and other adverse-event categories, and it gives percentages for selected serious adverse-event terms. Those data are descriptive. They do not constitute a randomized comparison, and the registry does not report that the listed events were caused by study treatment. The primary endpoint result itself is not reported in the registry record.

The study does not establish whether EVG+RTV is safer or less safe than another regimen. There is no control arm for that comparison. Nor can the entries establish a causal relationship between the regimen and an event: the participants had HIV-1 infection, received other antiretroviral agents, and were followed without a randomized comparator described in the record. General statistical explanation: observed events during a study can arise from treatment, underlying illness, concomitant therapies, or other circumstances; a single-group record cannot distinguish these explanations on its own.

The information also does not show how the primary endpoint varied across EVG doses or antiretroviral regimens. The registry describes more than one possible EVG dose, but does not report dose-specific endpoint estimates. It does not report uncertainty intervals or inferential tests for the primary endpoint. Thus, the record is informative about the study’s purpose, design, and selected safety summaries, but it does not provide a complete statistical answer to its primary safety question.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between its long-term safety objective and its single-group design. The registry describes follow-up up to Week 408 plus 30 days, but without a randomized comparator the study can primarily describe the safety observations recorded in this cohort. It cannot isolate treatment effects from other explanations for events or estimate a comparative effect against another regimen.

The primary endpoint is participant-based and asks whether any treatment-emergent study drug-related adverse event occurred. This makes it conceptually different from summaries of event counts or selected serious-event terms. A participant-level endpoint can capture whether an event occurred, but it does not by itself describe event frequency per person, severity, duration, or the full burden of repeated events. Here, the registry does not report the primary endpoint percentage, so that planned summary cannot be assessed.

The safety set is defined by receipt of at least 1 dose of EVG, while treatment included an antiretroviral regimen and could involve different EVG doses. This context matters when interpreting a cohort-level safety summary: the record does not report analyses that distinguish dose or regimen, and it does not provide a comparator to help separate possible treatment-related patterns from background events.

Finally, the registry record’s limited statistical detail is itself important. It does not report a detailed analysis plan, missing-data approach, or multiplicity procedure. These omissions do not prove that no such methods were used elsewhere, but they limit what can be concluded from the registry record. The study’s design and reporting support cautious description, not a claim of comparative benefit or harm.

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.

Several limitations are specific to interpreting this record. The study is single-group, open-label, and has no comparator group listed. It therefore cannot provide a randomized comparison with another antiretroviral regimen. Open-label status also means masking was not used, although the registry does not describe how event assessments were conducted or whether any independent review occurred.

Participants had completed a prior EVG+RTV treatment study. The findings therefore concern this study population and should not automatically be generalized to people without that prior study experience. The registry record does not report participant characteristics that would allow a more detailed assessment of how representative the group was.

The intervention included EVG with RTV and other antiretroviral agents. The registry describes EVG 85 mg or 150 mg according to regimen, and says some participants may receive EVG 300 mg during the protocol. It does not report safety results by EVG dose, concomitant regimen, duration of exposure, or other participant characteristics. This limits interpretation of variation in the treatment received.

The registry does not report the primary endpoint result, its numerator or denominator, or a confidence interval. The listed serious and other adverse-event counts and selected event-term percentages do not supply that missing endpoint result. The record also does not report detailed methods for missing data, multiplicity, endpoint assessment, or analysis. These gaps limit appraisal of precision, completeness, and the procedures used to produce the reported safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety of EVG+RTV Administered With Other Antiretroviral Agents for the Treatment of HIV-1 Infection — NCT00445146.
• Registry record last updated 2016-04-25; status last verified 2016-03.
• Results first posted 2016-04-25.
• 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

NCT00445146 is a completed phase 2, open-label, multicenter, single-group study of EVG boosted with RTV and given with other antiretroviral agents. It enrolled 192 participants who had completed a prior EVG+RTV treatment study. The primary safety endpoint was the percentage experiencing any treatment-emergent study drug-related adverse event up to Week 408 plus 30 days.

The registry record does not report the primary endpoint result or a statistical analysis plan. It lists 86 affected among 192 at risk for serious adverse events and 172 affected among 192 at risk for other adverse events, along with percentages for selected serious adverse-event terms. These entries are descriptive and do not provide a randomized comparison or establish causation.