Kaletra and Maraviroc in Antiretroviral Therapy (ART)-Naive Patients (KALMAR Study): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Kaletra and Maraviroc in Antiretroviral Therapy (ART)-Naive Patients (KALMAR Study) (NCT01068873), a na phase 4 study. The primary outcome is Assess Proportion of Participants With HIV RNA Levels <50 and < 400 Copies/mL..

2. Clinical Question

The clinical question is therefore about virologic outcomes during treatment with the two-drug combination in a small pilot study, rather than a comparative treatment effect. HIV RNA below the stated thresholds is used to describe viral suppression at specified levels. The record also lists secondary questions about suppression, time to suppression, change in viral load, CD4+ T cell count, resistance mutations, and co-receptor tropism changes.

The distinction between the planned study and the recorded study is important to interpretation. The brief summary states that twenty patients would be enrolled and studied for 48 weeks, but the registry enrollment is 1 and the study status is terminated. The reason for termination, the actual duration of participant follow-up, and the participant-level outcome values are not reported in the registry record. The record therefore does not support a numerical answer to the primary clinical question.

3. Trial Design

KALMAR is identified as a phase 4, open-label, single-group study of lopinavir/ritonavir plus maraviroc. It was sponsored by Temple University and concerned HIV infections. The registry lists the study as terminated. The start and primary completion dates are recorded as 2010-04 and 2010-12, respectively. Those dates do not establish how long any individual participant was followed.

The design has no randomized allocation and no separate control arm. The registry records allocation as not applicable, masking as none, and the model as single group. In practical terms, the intervention was administered in an open-label setting; the record does not describe a comparison that would separate the treatment experience from changes over time or other influences. It also does not report details of treatment administration, eligibility criteria beyond the broad population description, or procedures for maintaining follow-up.

The brief summary calls the study a pilot and describes a plan to enroll twenty patients and study them for 48 weeks. In contrast, the recorded enrollment is 1. This difference means that the planned cohort should not be mistaken for the number recorded as enrolled. The reason the recorded enrollment differs from the stated plan, and the reason the study was terminated, are not reported in the registry record.

The primary outcome is described as the proportion with HIV RNA below 50 and below 400 copies/mL at week 48. The outcome entry also labels the relevant population as a subject who terminated the study before week 48, leaving uncertainty about how the planned week 48 endpoint was handled for that participant. No denominator, outcome count, estimate, or analysis method for the primary endpoint is reported in the registry record. Seven outcome measures are recorded, while the number of analyses is 0. The registry entry therefore gives the study framework but not enough analysis detail to reproduce a treatment-effect estimate.

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

Analysis population for the primary outcome, as defined in the registry: Subject terminated study prior to week 48

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 Assess Proportion of Participants With HIV RNA Levels <50 and < 400 Copies/mL., measured over week 48.

The primary endpoint concerns the proportion of participants whose HIV RNA level is below the stated thresholds of 50 and 400 copies/mL at week 48. Viral load is a measure of HIV RNA in the blood. Expressing an endpoint as the proportion below a threshold turns each participant’s measured value into a classification for that threshold: below it or not below it. The two thresholds describe different levels of viral suppression and should be read as separate outcome definitions, not as a single combined threshold.

In general, a threshold-based endpoint can make a clinical study question easier to state and can support a direct estimate of how many participants meet a prespecified target. Its interpretation depends on when the measurement is taken, how missing or late measurements are treated, and which participants are included in the denominator. Those details matter particularly when follow-up does not extend to the planned assessment time.

In this record, the primary timeframe is week 48, but the primary outcome entry describes the population as a subject who terminated the study before week 48. The record does not explain how that description relates to an assessment at week 48 or specify the endpoint denominator and missing-data rule. It also does not report a number of participants meeting either threshold or an estimated proportion. Thus, the endpoint is identifiable as a question, but its observed result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the study as a single-group, open-label study and lists no analyses. It does not report a statistical analysis plan, an analysis model, a confidence-interval method, or a rule for handling missing observations. The explanations below describe general statistical concepts relevant to the stated outcomes; they should not be read as methods confirmed to have been used in KALMAR.

What does a threshold-based proportion measure?

For an outcome such as HIV RNA below 50 copies/mL at week 48, each participant assessed at the specified time is classified according to whether the measured level is below the threshold. The proportion is the number meeting the definition divided by the number included in that endpoint analysis. The same approach applies to the separate threshold of below 400 copies/mL. The two results can differ because the thresholds define different criteria.

General statistical context: the estimate alone does not describe its precision. A confidence interval expresses uncertainty around an estimated proportion under a specified statistical method and its assumptions. With a small denominator, the estimate can vary markedly depending on the outcome of an individual participant, and the interval may be broad. Neither an estimate nor its interval can be reconstructed from the registry entry because the outcome count and analysis denominator are not reported.

Why does the denominator matter?

A week 48 proportion requires a rule for deciding who belongs in the denominator. Some participants may lack a measurement at the planned time, discontinue, or have a measurement outside the target visit window. General statistical practice requires a transparent rule for these cases because counting only participants with observed measurements can produce a different result from treating missing outcomes another way. The registry’s primary outcome description refers to a subject who terminated before week 48, but the handling of that observation and the endpoint denominator are not reported in the registry record.

General statistical context: missingness is not only a loss of information; it can also affect interpretation if the reasons for missing measurements are related to participants’ outcomes. Statistical methods can make assumptions about unobserved outcomes, but those assumptions need to be stated and assessed. No such method or assessment is reported in the registry record. Termination should not be treated as evidence of either success or failure on the virologic endpoint without an explicit outcome rule and observed data.

What can a single-group design estimate?

A single-group study can describe outcomes among the participants observed while receiving the intervention. It does not include a separate randomized group that provides a contemporaneous comparison. General statistical context: without that comparator, an observed change over time cannot by itself distinguish an intervention-related effect from other explanations, such as the natural course of outcomes, changes in care, or differences between participants who remain in follow-up and those who do not. These are design considerations, not claims about what occurred in this study.

The record marks masking as none and the study as open label. General statistical context: knowledge of assigned treatment can affect some aspects of measurement, reporting, or clinical management, depending on the outcome and study procedures. The threshold-based HIV RNA outcome is a laboratory measure, but the record does not specify laboratory procedures or whether outcome assessment was otherwise masked. No assumption about those procedures is warranted.

How should the listed planning assumptions be read?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It defines the effect to detect as a stated fraction of the observed effect. For time-to-event illustrations, it describes totals of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These are planning assumptions, not a description of the KALMAR design, which is recorded as single group.

General statistical context: a sample-size calculation estimates how much information a hypothetical study might need under its assumptions. It does not report how many participants were actually enrolled, establish that a study had a particular probability of detecting an effect, or show that an effect occurred. Sample-size values used for planning are not observed power. Because no primary outcome estimate is reported in the registry record, the stated basis of an observed effect cannot be evaluated from this entry. The planning assumptions should therefore be distinguished from the study’s recorded enrollment and from any treatment-effect conclusion.

What does the record leave unspecified?

The registry does not report the statistical method used for the primary endpoint, the analysis population, a prespecified missing-data approach, or whether any sensitivity analyses were conducted. It also does not report an adjusted analysis or a method for calculating uncertainty. General statistical context: these choices can affect how an estimate is formed and how strongly it depends on assumptions, particularly when follow-up is incomplete. Without a stated method and outcome data, readers cannot reproduce an estimate or determine whether different reasonable analytical choices would alter the interpretation.

The secondary outcomes include both threshold proportions and other types of outcomes, such as time to viral suppression, changes in viral load and CD4+ T cell count, and resistance or tropism changes. Different outcome types can call for different statistical approaches. The registry lists no analyses, so it is not possible to say which methods, if any, were used for these outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The record lists multiple outcome questions in addition to the primary endpoint. These include viral suppression at two HIV RNA thresholds, suppression at study termination, time to suppression, viral-load changes at several assessment times, CD4+ T cell changes, and resistance and tropism outcomes. When a study evaluates multiple outcomes or time points, general statistical context is that the chance of at least one apparently notable result can increase if each is tested separately. Methods for addressing that issue depend on the objectives and analysis plan.

A multiplicity strategy, hierarchy among outcomes, or distinction between confirmatory and exploratory analyses is not reported in the registry record. The record lists 0 analyses, so it does not identify tests or estimates to which an adjustment could be applied. It is therefore not possible to judge how multiplicity was handled or whether any reported secondary finding was intended as confirmatory. No secondary results are reported in the registry record.

The entry does not report an analysis population or a missing-data method. The primary outcome entry’s description of a subject who terminated before week 48 makes the handling of incomplete follow-up particularly relevant, but does not state how that subject was classified or whether a week 48 measurement was available. General statistical context: excluding participants without a measurement, counting them as not meeting a threshold, or using a model-based approach can lead to different estimands and assumptions. The record does not specify which approach applied.

It is also not reported in the registry record whether the analyses were based on all enrolled participants, participants who received treatment, or participants with an available outcome. These populations are not interchangeable. With enrollment recorded as 1, a transparent account of participant disposition and endpoint availability would be essential to interpret any proportion, but those details are not reported.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The safety entry describes an open-label single arm with 1 participant at risk for serious adverse events and 0 serious adverse events reported. It also records 1 participant at risk for other adverse events and 0 other adverse events, with 0 deaths. No serious adverse-event terms are listed.

These figures are counts in the registry record, not estimates of risk for a broader population. With only 1 participant recorded as at risk, zero reported events do not establish that an event could not occur or that the intervention has no safety concerns. The record does not report the duration of that participant’s exposure, the method for collecting adverse events, or whether the safety observation period matched the planned 48-week follow-up.

General statistical context: an observed count of zero is different from proof of zero underlying risk. Precision depends on the number of participants observed, time at risk, event definitions, and completeness of reporting. The single-arm design also provides no comparative safety estimate against another group. The registry figures should therefore be read narrowly as the event counts recorded for the stated group, not as a comparative or definitive safety assessment.

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

The registry record establishes that KALMAR was intended to assess lopinavir/ritonavir plus maraviroc in antiretroviral-naïve patients with HIV infection. Its stated primary question concerned the proportion with HIV RNA below 50 and below 400 copies/mL at week 48. The record identifies a phase 4, open-label, single-group design and a terminated status. Those details describe the study’s scope and structure, but they do not provide the primary outcome result.

The brief summary describes a planned enrollment of twenty patients, whereas recorded enrollment is 1. The reason for the difference and for termination is not reported in the registry record. No participant-level measurements, outcome counts, endpoint denominators, estimates, confidence intervals, or statistical analyses are reported. The primary outcome entry’s reference to a subject who terminated before week 48 does not say whether the primary endpoint was measured or how a missing week 48 result was treated.

Accordingly, the registry entry cannot establish the proportion meeting either viral-load threshold, describe the precision of such a proportion, or support a comparison with another treatment. Since there is no separate control group, even a reported change among observed participants would have been a within-group description rather than a randomized comparative effect. The record also does not provide results for its secondary questions concerning suppression over time, viral-load and CD4+ T cell changes, resistance, or tropism.

The safety record reports 0 serious adverse events, 0 other adverse events, and 0 deaths in a group with 1 participant at risk. Those counts should not be interpreted as proof that adverse events are impossible or as evidence of comparative safety. They describe the registry’s recorded counts only.

In general, a trial result is interpreted by considering the estimated effect, its uncertainty, the design, and the completeness of outcome reporting. In this case, the missing outcome estimates prevent a quantitative assessment. The appropriate reading is limited: the registry records the study’s aim and design, but does not report results that answer its primary clinical question.

13. Why This Trial Matters Statistically

This study is statistically instructive because its planned scope and recorded enrollment differ substantially in what they allow a reader to conclude. The brief summary describes a pilot intended to enroll twenty participants and follow them for 48 weeks, while the registry records enrollment of 1 and marks the study terminated. Planning targets describe what a study intended to do; they are not evidence that the planned number was enrolled or assessed.

The entry also illustrates the importance of distinguishing a stated endpoint from a reported result. It defines a clinically interpretable question using HIV RNA thresholds at week 48, but does not report the number meeting either threshold, the denominator, or an estimate with uncertainty. Without those elements, a reader cannot judge the observed proportion or its precision. The endpoint’s description of a participant terminating before week 48 further highlights the need for explicit outcome and missing-data rules.

The single-group, open-label design is another key statistical feature. It can describe experience within the group, but cannot supply the same comparative evidence as a randomized control group. This is not a defect to be resolved by statistical adjustment after the fact; it is a limit on the kinds of causal contrasts the design can estimate.

The record’s safety counts also show why denominators and observation time matter. Zero reported events among a group with 1 participant at risk is a limited observation, not a precise general estimate. More broadly, the entry demonstrates that a registry may state a detailed set of outcome questions while providing no corresponding analyses or results. Clear reporting of participant flow, endpoint availability, analysis populations, and uncertainty is necessary for readers to move from a study objective to an interpretable estimate.

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.

Several limitations specific to this record constrain interpretation. First, the registry lists enrollment as 1, although the brief summary describes a plan to enroll twenty patients. The record does not explain the discrepancy, identify the reason for termination, or describe participant flow. The actual extent of follow-up is also not reported, so the planned 48-week study period should not be assumed to represent the observed follow-up of the recorded participant.

Second, the primary endpoint is defined by HIV RNA thresholds at week 48, while its population description refers to a subject who terminated before week 48. The record does not clarify whether a week 48 measurement was available, how termination affected the endpoint, or what denominator was intended. No numerator, proportion, estimate of uncertainty, or analysis method is reported in the registry record.

Third, the single-group, open-label design contains no randomized comparator. Any outcome reported from the group would not, by itself, provide a controlled estimate of how the combination compares with another intervention. The record does not report details about dose, adherence, concomitant care, participant characteristics, laboratory procedures, or assessment masking, limiting further evaluation of conduct and applicability.

Finally, the registry lists several secondary outcome questions but no analyses. It does not report a multiplicity approach, an analysis population, missing-data procedures, or sensitivity analyses. The reason these details are absent is not reported in the registry record. The safety counts are also based on a group with 1 participant at risk and do not support a precise general safety estimate. These limitations mean that the record is informative about the study’s stated intent, but not about the magnitude, precision, or comparative interpretation of clinical outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Kaletra and Maraviroc in Antiretroviral Therapy (ART)-Naive Patients (KALMAR Study) — NCT01068873.
• Registry record last updated 2020-11-02; status last verified 2020-10.
• Results first posted 2020-11-02.
• 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.

18. Record Summary

NCT01068873 is the KALMAR study, a phase 4, open-label, single-group study sponsored by Temple University. It examined lopinavir/ritonavir plus maraviroc in antiretroviral-naïve patients with HIV infection. The registry records enrollment of 1, study status as terminated, a start date of 2010-04, and a primary completion date of 2010-12. The brief summary describes a plan to enroll twenty patients for 48 weeks.

The primary outcome question concerns the proportion with HIV RNA below 50 and below 400 copies/mL at week 48. The primary outcome population is described as a subject who terminated before week 48. No primary or secondary outcome estimates or analyses are reported in the registry record. The safety entry records 0 serious adverse events, 0 other adverse events, and 0 deaths among 1 participant at risk. These entries describe the recorded study, but do not provide a comparative treatment estimate or a precise population-level assessment.