This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Kaletra in Combination With Antiretroviral Agents (NCT01076179), a registered phase not stated study. The primary outcome is Prevalence of Adverse Events (Weeks 0-144), Per Event.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01076179 |
| Phase | Phase not stated |
| Condition | Human Immunodeficiency Virus |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 502 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AbbVie (prior sponsor, Abbott) |
| Results posted | Yes |
2. Clinical Question
Population
HIV-infected participants. The registry record lists enrollment of 502 participants, and describes the study group as participants taking Kaletra with an integrase inhibitor, non-nucleoside reverse transcriptase inhibitor, or CCR5 antagonist.
Intervention
Combination treatment with Kaletra (lopinavir/ritonavir) and one of the newer antiretroviral agent types named in the record. The record does not identify the specific new substances used by individual participants or state how those choices were made.
Comparator
No like-for-like control comparison is described. The registry record does not state an allocation method, and its design information cautions that this is not a randomized comparison.
Primary question
How were adverse events distributed by event type during Weeks 0 to 144 among participants receiving Kaletra with newer antiretroviral agents? The primary endpoint is framed as the percentage of the overall number of adverse events represented by each event type, rather than as the percentage of participants experiencing an event.
The stated purpose was to investigate tolerability when Kaletra was combined with newer substances, including integrase inhibitors, CCR5 antagonists, and newer non-nucleoside reverse transcriptase inhibitors. The record describes reasons a change from routine treatment might occur, such as intolerability, complex resistance patterns, or personal reasons. It does not establish that every participant changed treatment for any particular reason, nor does it report a comparison with participants who continued another regimen.
Several secondary outcomes concern CD4 cell-count changes and resistance to lopinavir or protease inhibitors. These outcomes give the study a broader scope than the primary adverse-event question, but their listed titles do not establish what their results were.
3. Trial Design
The registry record identifies this as a study of HIV-infected participants taking Kaletra with integrase inhibitors, non-nucleoside reverse transcriptase inhibitors, or CCR5 antagonists. The enrollment is 502. The record lists the study as completed, with a start date of 2008-09 and primary completion in 2016-01. AbbVie is identified as sponsor, with Abbott noted as the prior sponsor.
The design information says that this was not a randomized comparison and that allocation was not stated. It also cautions that the arms are not a like-for-like control comparison. Consequently, the record does not describe a randomized treatment contrast from which the effect of one regimen versus another could be isolated. It does not state whether participants were assigned to particular new agents, whether choices reflected clinical decisions, or how long each participant used each combination.
The primary outcome concerns the prevalence of adverse events during Weeks 0 to 144, reported per event type. Doctors asked participants about adverse events and grouped reported events into categories listed in the electronic case report form. Those categories included laboratory abnormalities and symptoms. The registry record does not report the actual primary outcome values by category.
The secondary outcome list includes changes in absolute CD4 cell count, CD4 increases of at least 100 cells/μL, time to such an increase, and lopinavir or protease-inhibitor resistance at baseline and during follow-up. The list names modified intent-to-treat and as-treated analyses for one CD4 outcome, but it does not give analysis methods or results for those outcomes. No analysis results are listed 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.
Overall Study
| Stage | HIV-infected Participants |
|---|---|
| STARTED | 502 |
| COMPLETED | 501 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | HIV-infected Participants |
|---|---|
| Withdrawal by Subject | 1 |
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.
| Characteristic | Unit | HIV-infected Participants |
|---|---|---|
| Participants analysed | 501 | |
| Age, Continuous | years | 45.4 (SD 11.1) |
| Sex: Female, Male: Female | Participants | 70 |
| Sex: Female, Male: Male | Participants | 431 |
6. Primary Endpoint
The registry lists the primary outcome as Prevalence of Adverse Events (Weeks 0-144), Per Event, measured over Weeks 0 to 144.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled prevalence of adverse events during Weeks 0 to 144, per event. Its description defines the reported quantity as the percentage of the overall number of adverse events represented by each adverse-event type. Doctors asked participants about adverse events and grouped them into categories in the electronic case report form. Listed categories include lipid and glucose abnormalities, elevated liver-related laboratory measures, and symptoms such as nausea, diarrhea, abdominal pain, headache, fatigue, and fever.
This type of endpoint can describe the composition of the recorded adverse-event total: it indicates how much of that total was attributed to each category. It is not, by itself, the proportion of participants who experienced an event. A participant may experience more than one event, and an event-category percentage does not give the participant-level risk unless the endpoint and denominator are defined that way.
General statistical context: describing event types can help characterize tolerability patterns, while participant-level summaries address how many people experienced an event. These answer different questions and should not be treated as interchangeable. The registry record does not report the category-specific primary outcome values, so the distribution of event types cannot be interpreted from the record information available. It also does not report a confidence interval or a comparison for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record states the study’s purpose and identifies its primary adverse-event endpoint, but it does not report the primary outcome values. The endpoint is intended to express each adverse-event type as a percentage of the overall number of adverse events during Weeks 0 to 144. Without those category-specific values, it is not possible to say which listed event types were more or less common in the primary outcome, or how precisely their percentages were estimated.
The record lists enrollment of 502. For the serious-adverse-event information, 501 participants are listed as at risk and 30 as affected. These figures describe the safety record’s participant counts; they do not provide the missing primary endpoint distribution. Nor do they give a treatment comparison. The serious-event terms listed include diarrhea at 0.8%, and lymphadenopathy, multi-organ failure, increased gamma-glutamyltransferase, hyponatremia, and cough at 0.4% each. The record does not give event counts alongside these term percentages or explain their denominator in the information available.
The absence of a randomized comparison matters for causal interpretation. Participants taking different newer agents may differ for reasons related to clinical choice or other factors; the registry record does not provide enough detail to assess those factors. The record explicitly cautions that the arms are not a like-for-like control comparison. Thus, even if results were available by group, a difference would not automatically establish that the regimen caused the difference.
The record lists 20 outcome measures and 0 analyses. It names secondary outcomes involving CD4 cell counts and resistance, but outcome titles alone do not show the direction, size, or precision of any findings. Statistical significance, confidence intervals, and adjusted comparisons are not reported in the registry record. The same is true of the primary endpoint values.
General statistical context: precision depends on the amount and variability of the data, and is usually conveyed by an interval estimate. A percentage without an interval can be difficult to judge because it may be estimated with more or less uncertainty. Here, the registry record does not provide primary endpoint estimates or intervals to assess. The available information therefore supports a description of the question, design cautions, and recorded safety figures, but not a conclusion about comparative treatment effects.
9. Statistical Methods Explained
The central statistical issue is the distinction between a descriptive event distribution and a comparative treatment effect. The primary endpoint describes adverse events by category as a percentage of all adverse events during Weeks 0 to 144. Its stated denominator is the overall number of adverse events, not the number of participants. This describes the mix of recorded events. It does not directly estimate the probability that a participant experiences a particular event.
What does a percentage of events represent?
General statistical context: when each event is the unit being counted, a person with repeated events can contribute more than once. The resulting proportion is therefore about recorded events, not necessarily about people. A participant-level risk requires a participant denominator and a clear definition of who counts as having experienced the outcome. The endpoint description identifies an event-level denominator, while participant-level event risks are not reported for the primary endpoint.
Event-level data can also have a dependence structure: multiple events from the same participant may be related. General statistical context: methods that treat every event as independent can give an incomplete account of uncertainty when repeated events cluster within people. The registry record does not report how repeated events were handled, whether event-level analyses accounted for clustering, or whether events were counted once or repeatedly under any particular rule. Those details are not reported in the registry record.
What does the design permit?
The record says allocation was not stated and warns that the arms are not a like-for-like control comparison. General statistical context: random allocation is one way to make groups comparable, on average, with respect to both known and unknown factors at baseline. When a study is not described as randomized, observed group differences may reflect differences in participants, treatment selection, follow-up, or other factors, as well as treatment. The record does not give enough information to determine which factors were measured or adjusted for. It therefore does not support interpreting a between-group contrast as a causal effect.
The record describes one group of HIV-infected participants on Kaletra with integrase inhibitors, non-nucleoside reverse transcriptase inhibitors, or CCR5 antagonists. It does not specify the exact agents, exposure patterns, or analysis contrasts. General statistical context: combining multiple regimens in a broad group can make an overall description useful for characterizing that group, but it may obscure differences among the specific combinations. Whether such subgroup analyses were planned or conducted is not reported in the registry record.
How should uncertainty and significance be read?
General statistical context: a confidence interval expresses the range of values compatible with the data and a stated statistical procedure. Its width communicates precision; a wide interval indicates greater uncertainty than a narrow one. A p-value addresses compatibility between data and a specified null model, but does not measure the size or importance of an effect. Neither confidence intervals nor p-values for the primary endpoint are reported in the registry record. No inferential comparison for that endpoint is listed.
For count outcomes, variability can exceed what a simple Poisson model assumes, a situation commonly called over-dispersion. General statistical context: if over-dispersion is present and not addressed, standard errors and interval estimates may be too small. The primary endpoint is expressed as a percentage of events, and the record does not identify a count model, an over-dispersion assessment, or a method for estimating uncertainty. It is therefore not possible to assess those modeling choices from the registry record.
What is the role of planning illustrations?
The sample-size assumptions describe a planning illustration computed from an observed effect, not the trial’s own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The note distinguishes total event counts for time-to-event illustrations from participants per arm for other illustrations.
General statistical context: planning calculations ask how much information might be needed under stated assumptions. They do not establish what the study was designed to detect, and they are not a measure of observed power. Any planning illustration should not be read as evidence that the study did or did not detect a treatment effect. The registry record does not report the trial’s own sample-size justification or design assumptions beyond the planning note.
Because the registry record lists 0 analyses and provides no primary outcome estimates, the statistical methods actually used to analyze the primary endpoint are not reported in the registry record. In particular, the record does not report the treatment contrasts, uncertainty estimates, model specification, covariate adjustment, or handling of repeated events.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 20 outcome measures, including the primary adverse-event outcome and secondary outcomes related to CD4 cell counts and resistance. It lists 0 analyses and does not provide results for these outcomes. The record does not report whether a hierarchy of outcomes, multiplicity adjustment, or other strategy for interpreting multiple statistical tests was used.
General statistical context: when many outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. A prespecified hierarchy or adjustment can help define how evidence across multiple tests should be interpreted. Without a reported plan, it is not possible to determine how any collection of findings was intended to be interpreted. No claims about the presence or absence of multiplicity adjustment can be made from the outcome list alone.
The secondary outcome titles refer to modified intent-to-treat and as-treated analyses for the CD4 increase outcome. These names indicate that different analysis populations were contemplated for that outcome, but the registry record does not report the population definitions, exclusions, or results. The primary outcome population is not specified in its description. How missing outcome data were handled, whether follow-up differed between participants, and whether sensitivity analyses were conducted are not reported in the registry record.
The registry record also does not report interim analyses, stopping rules, or the statistical analysis plan. Those omissions limit assessment of how outcomes and analyses were selected and how incomplete data may have affected results. The absence of these details does not establish that a method was not used; it means the method is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| HIV-infected Participants | 30 | 501 | 6.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| HIV-infected Participants | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | HIV-infected Participants |
|---|---|---|
| DIARRHOEA | Gastrointestinal disorders | 4 of 501 |
| LYMPHADENOPATHY | Blood and lymphatic system disorders | 2 of 501 |
| MULTI-ORGAN FAILURE | General disorders | 2 of 501 |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | Investigations | 2 of 501 |
| HYPONATRAEMIA | Metabolism and nutrition disorders | 2 of 501 |
| COUGH | Respiratory, thoracic and mediastinal disorders | 2 of 501 |
| NEUTROPENIA | Blood and lymphatic system disorders | 1 of 501 |
| CARDIAC FAILURE | Cardiac disorders | 1 of 501 |
| ABDOMINAL PAIN | Gastrointestinal disorders | 1 of 501 |
| NAUSEA | Gastrointestinal disorders | 1 of 501 |
Serious events with the highest arm-level rate: diarrhoea (0.8%), lymphadenopathy (0.4%), multi-organ failure (0.4%), gamma-glutamyltransferase increased (0.4%), hyponatraemia (0.4%).
The safety information lists 501 participants as at risk and 30 as affected by serious adverse events. These are participant counts in the serious-adverse-event record. They are separate from the primary endpoint, which describes the percentage of all adverse events represented by each event type. They should not be combined into a single measure.
The listed serious-event terms are diarrhea at 0.8%, lymphadenopathy at 0.4%, multi-organ failure at 0.4%, increased gamma-glutamyltransferase at 0.4%, hyponatremia at 0.4%, and cough at 0.4%. These are term percentages as recorded; the registry record does not state the denominator or provide event counts for these terms in the information available. They should not be read as percentages of all enrolled participants unless the denominator is explicitly established.
The record does not report a death count. That means deaths are not reported in the registry record; it does not establish that no deaths occurred. Likewise, the listed terms do not necessarily represent every serious adverse event recorded. The information does not give a randomized control comparison, so these figures describe the recorded safety experience rather than a comparative estimate attributable to a particular regimen.
12. What the Result Does, and Does Not, Mean
The record establishes that the study examined tolerability of Kaletra combined with newer antiretroviral agents in HIV-infected participants. It identifies an adverse-event endpoint covering Weeks 0 to 144 and lists the types of event categories considered. The safety record also lists 30 participants affected by serious adverse events among 501 at risk, along with several serious-event terms and their recorded percentages.
Those details do not establish the prevalence of each primary-endpoint category, because its category-specific values are not reported in the registry record. They also do not establish how many participants experienced each type of non-serious adverse event. The primary endpoint uses the overall number of adverse events as its denominator, so it describes the event mix rather than participant-level risk.
The registry record does not describe a randomized comparison, and it explicitly warns that the arms are not a like-for-like control comparison. The posted information therefore cannot establish that a difference between treatment groups was caused by a particular combination. The record does not provide the analyses, confidence intervals, or statistical tests needed to assess comparative estimates.
General statistical context: a descriptive result can characterize observations in a study group without demonstrating that the same pattern would occur in another group or under another treatment. A causal conclusion requires a design and analysis that address alternative explanations. The design details and results available in the registry record are insufficient for that purpose.
The record also does not establish the efficacy of any regimen. Although it lists secondary outcomes for CD4 cell counts and resistance, it does not report their results. The study’s stated focus is tolerability, but the outcome titles alone do not show whether a particular combination was better or worse on safety, immune status, or resistance. The appropriate interpretation is limited to the study question, the recorded safety counts, and the substantial gaps in reported outcome and analysis information.
13. Why This Trial Matters Statistically
This study raises a useful statistical distinction: an event-level percentage and a participant-level risk answer different questions. Reporting each adverse-event type as a percentage of all events describes the composition of the event record. It does not tell a reader directly what proportion of participants experienced a given event. Keeping the denominator explicit is essential when interpreting tolerability summaries.
The study also illustrates why design information is part of statistical interpretation. The registry record says allocation was not stated and cautions that the arms are not a like-for-like control comparison. That warning limits what can be inferred from any apparent group differences. A numerical contrast, without a suitable comparison design and relevant analysis details, does not by itself isolate a treatment effect.
The record’s broad treatment description covers integrase inhibitors, non-nucleoside reverse transcriptase inhibitors, and CCR5 antagonists in combination with Kaletra. This breadth makes it important to know whether results are reported for the overall group or separately by agent and regimen. The record does not provide those results or analyses, so the possible variation among combinations cannot be assessed.
Finally, a registry outcome list is not a substitute for outcome estimates and methods. Here, the listed secondary outcomes identify questions about CD4 cell counts and resistance, but no analyses are listed. The absence of estimates, uncertainty measures, and information about missing data limits the statistical conclusions that can be drawn. Recognizing those boundaries is part of reading clinical evidence accurately, especially when the stated endpoint is descriptive and the design is not a like-for-like comparison.
14. 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 most direct limitation is that primary outcome values are not reported in the registry record. The endpoint description explains how adverse events were categorized and defines the percentage in relation to the total number of adverse events, but it does not give the percentages by category. The registry record therefore cannot show the primary event distribution or its precision.
The study is not described as a randomized comparison, and allocation is not stated. The record explicitly cautions that the arms are not a like-for-like control comparison. This limits interpretation of differences between groups and prevents attributing any observed contrast to treatment without further design and analysis information.
The treatment description groups several classes of newer agents with Kaletra. Specific agents, participant-level regimens, treatment choices, exposure durations, and relevant group definitions are not reported in the registry record. It is not possible to assess whether outcomes varied across particular combinations or whether treatment groups differed in other important respects.
The record lists 20 outcome measures but 0 analyses. It does not report primary-endpoint estimates, confidence intervals, p-values, analysis methods, or results for the secondary outcomes. Missing-data handling, analysis-population definitions for the primary endpoint, and sensitivity analyses are also not reported. The secondary-outcome titles naming modified intent-to-treat and as-treated analyses do not supply their definitions or findings.
The serious-adverse-event record gives participant counts and term percentages, but does not state the denominator for the listed term percentages in the information available. A death count is not reported. These limitations constrain interpretation of both the primary endpoint and the broader safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Kaletra in Combination With Antiretroviral Agents — NCT01076179.
- Registry record last updated 2017-05-19; status last verified 2017-05.
- Results first posted 2017-05-19.
- 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.
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18. Record Summary
The registry record describes a completed study of Kaletra (lopinavir/ritonavir) combined with integrase inhibitors, non-nucleoside reverse transcriptase inhibitors, or CCR5 antagonists in HIV-infected participants. Enrollment was 502. The listed start date is 2008-09 and primary completion is 2016-01. AbbVie is identified as sponsor, with Abbott noted as the prior sponsor.
The primary endpoint concerns adverse-event types during Weeks 0 to 144, expressed as percentages of the overall number of adverse events. The record lists 20 outcome measures and 0 analyses. Primary outcome values and results for the listed secondary outcomes are not reported in the registry record.
The safety information lists 501 participants at risk and 30 affected by serious adverse events, with several serious-event terms and percentages. The record cautions that this was not a randomized comparison and that the arms are not a like-for-like control comparison. These design and reporting limits restrict comparative and causal interpretation.