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 Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients (NCT03360682), a non-randomized phase 4 study. The primary outcome is Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03360682 |
| Phase | Phase 4 |
| Condition | HIV-1-infection, Solid Organ Transplant |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Fundacion Clinic per a la Recerca Biomédica |
| Results posted | Yes |
2. Clinical Question
Population
People with HIV-1 infection who had received a solid organ transplant. The registry record lists 19 enrolled participants and describes two groups distinguished by whether the patient or donor had genetic characteristics associated with severe abacavir allergy, or whether the patient carried hepatitis B virus.
Intervention
The study examined a dolutegravir-based regimen with two nucleoside reverse transcriptase inhibitors. The listed drugs are dolutegravir, lamivudine, abacavir, tenofovir disoproxil and emtricitabine. The record describes treatment for 48 weeks, but does not specify which exact combination each participant received.
Comparator
There was no randomized or like-for-like control group. The registry identifies a nonrandomized, single-arm pilot trial. Its two described groups reflect eligibility characteristics, rather than a randomized comparison of treatment strategies.
Primary question
The primary endpoint was the change in cyclosporine A pharmacokinetic parameters, specifically Cmax and Cmin, assessed 24-hours before switching and 24-hours 2 weeks after switching. The broader study aim was to obtain pharmacokinetic information on interactions between dolutegravir and immunosuppressant drugs in solid organ transplant recipients, alongside an assessment of safety and efficacy. The registry record does not report the observed Cmax or Cmin results, so the size and direction of any change cannot be described.
3. Trial Design
This was a Phase 4, completed, nonrandomized pilot study. The registry record lists an enrollment of 19 and identifies HIV-1 infection and solid organ transplant as the conditions studied. The trial was unmasked, with no masking reported. Its model is listed as parallel, but the record also characterizes the study as single-arm and explicitly indicates that the arms are not a like-for-like control comparison. The group descriptions distinguish participants according to abacavir allergy-related genetic characteristics in the patient or donor, or hepatitis B virus carrier status in the patient.
The intervention list includes dolutegravir 50 mg, lamivudine 300 MG, abacavir 600 MG, tenofovir disoproxil 245Mg Tablet and emtricitabine 200 MG. The record does not map each drug to the individual participants or state the exact regimen received in each group. It describes treatment for 48 weeks. The primary pharmacokinetic comparison was scheduled around switching treatment: 24-hours before the switch and 24-hours 2 weeks after switching. These are the stated measurement time points; the registry record does not report the measurements themselves.
The stated aim was to collect pharmacokinetic information on interactions between dolutegravir and cyclosporine A, tacrolimus, sirolimus and mycophenolic acid, and to provide proof-of-principle data about the regimen in this population. The primary outcome specifically names cyclosporine A. Listed secondary outcomes include viral resistance, changes in CD4+ cell, lipid profile, renal function, and safety measured by the number of adverse events and serious adverse events. The registry record does not report a statistical analysis plan or outcome analysis records.
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: HIV-1-infected adults (\>18) with kidney, liver, or heart transplant, on stable ART ≥6 months, HIV RNA \<50 c/mL for 12 months, no major resistance mutations, and HLA-B\*5701 negative. Some participants had switched to DTG + 2 NRTIs within the 48 weeks prior to study inclusion, while others switched at the time of enrollment. All participants were followed for 48 weeks from the start of DTG-based ART.
Overall Study
| Stage | DTG + 2 NRTIs |
|---|---|
| STARTED | 19 |
| COMPLETED | 16 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | DTG + 2 NRTIs |
|---|---|
| Adverse Event | 3 |
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 | DTG + 2 NRTIs |
|---|---|---|
| Participants analysed | 19 | |
| Age, Continuous | years | 57 (51 to 60) |
| Sex: Female, Male: Female | Participants | 8 |
| Sex: Female, Male: Male | Participants | 11 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant, measured over 24-hours before the switch and 24-hours 2 weeks after switching.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns changes in the pharmacokinetic parameters Cmax and Cmin for the immunosuppressant cyclosporine A. Cmax refers to the maximum measured concentration over the stated measurement period, while Cmin refers to the minimum or trough concentration. Pharmacokinetic measurements describe drug exposure and concentration over time. In a study of people taking immunosuppressant drugs, comparing these measures around a treatment switch can help characterize whether concentrations changed in temporal association with the switch. That is a measurement question, not by itself proof that one drug caused a change.
The registry specifies a median as the summary measure and an inter-quartile range as the dispersion measure, with concentrations expressed in ng/mL. A median gives the middle of the observed values and is less influenced by extreme observations than a mean. The inter-quartile range describes the spread of the middle portion of the observations. These summaries can be useful when values are skewed or when a small study makes distributional assumptions difficult to assess. This is a general statistical explanation, not a claim about the distribution of the trial measurements.
The stated assessment points are 24-hours before the switch and 24-hours 2 weeks after switching. However, the observed medians, inter-quartile ranges, participant-level counts, and estimated change are not reported in the registry record. The primary endpoint therefore defines what was intended to be measured, but the posted record does not permit a numerical account of the observed pharmacokinetic change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically focused pharmacokinetic question: whether cyclosporine A Cmax and Cmin changed around a switch to a dolutegravir-based regimen in solid organ transplant recipients with HIV-1 infection. It specifies the summary approach and measurement timing, but does not report the observed endpoint values. There is therefore no reported numerical estimate of the change, no reported interval describing its precision, and no reported statistical test for this primary endpoint. The direction, size, and uncertainty of the observed change cannot be determined from the posted record.
The study enrolled 19 participants and was described as a nonrandomized, single-arm pilot. Its eligibility-defined groups are not a randomized treatment comparison, and the registry record warns against treating them as like-for-like controls. Consequently, the record cannot support a causal contrast between treatment strategies based on these group labels. Even if outcome values were available, interpretation would need to account for the absence of a randomized comparator and the limited enrollment. Those design features affect what can be learned from the study; they do not establish whether an individual participant experienced a change.
Safety reporting lists 19 participants at risk for serious events, 1 affected participant, and 0 deaths. It also lists 19 at risk for other adverse events and 15 affected participants. Cytomegalovirus infection is the serious-event term listed with 5.3%. These figures describe the registry’s reported counts and term; the record does not provide event-level details, timing, attribution, severity grading beyond the serious-event category, or a comparative safety analysis. The participant counts should not be read as the total number of event episodes.
The registry lists secondary outcomes including viral resistance, CD4+ cell changes, lipid profile, renal function and adverse events, but numerical results for those outcomes are not reported in the registry record. No analysis records are listed. Thus, the available information identifies the questions and some safety counts, rather than establishing an efficacy or pharmacokinetic conclusion. The record’s completed status indicates the study is marked complete; it does not supply the missing outcome estimates.
In short, this record describes a small exploratory study design and its intended pharmacokinetic endpoint. It does not provide enough reported results to quantify the primary change, assess its precision, or determine whether the observed data are compatible with a range of effects. Any planning illustration based on an observed effect should be understood as a design exercise, not as observed power or a substitute for the unreported endpoint results.
9. Statistical Methods Explained
The registry describes the primary outcome using medians and inter-quartile ranges. These are descriptive summaries: the median indicates the center of a set of values, and the inter-quartile range indicates its spread. They do not, on their own, estimate a treatment effect with a stated level of uncertainty. The record identifies Cmax and Cmin in ng/mL for cyclosporine A, but does not report their observed summaries or an estimated change between the stated assessment points.
What does a pharmacokinetic change measure?
Pharmacokinetics concerns how drug concentrations vary over time. Cmax and Cmin capture different parts of a concentration profile: a maximum and a minimum. A change in either measure can be described as a difference between measurements, but its interpretation depends on the values observed, the measurement conditions, and the variability among participants. The registry identifies a measurement before switching and a measurement 24-hours 2 weeks after switching. It does not report how many participants contributed paired measurements, how missing measurements were handled, or whether the recorded values were summarized as individual changes or as separate time-point summaries.
That distinction matters statistically. A paired analysis uses measurements from the same participant at both times and can account for within-participant similarity. A comparison of separate group summaries does not necessarily preserve that pairing. The analysis method used for the primary endpoint is not reported in the registry record, so it is not possible to say which approach was applied. This is a general distinction between analysis strategies, not a claim that either was used in this trial.
Why report both a center and a spread?
A center summary conveys a typical value, while a spread summary shows how much observations vary. The median and inter-quartile range can be informative when values are unevenly distributed or affected by unusually high or low observations. They do not reveal the full distribution: different datasets can share the same median and inter-quartile range. A confidence interval, if reported, would add an estimate of uncertainty around a parameter or effect. No confidence interval for the primary endpoint is reported in the registry record. Without the observed summaries and an uncertainty measure, the precision of the pharmacokinetic estimate cannot be assessed.
In general, small studies can yield unstable estimates because each participant’s data may have substantial influence on the summary. This is especially relevant when outcomes are variable. The enrollment of 19 is reported, but the endpoint-specific number analyzed is not. It would therefore be inappropriate to assume that all enrolled participants contributed usable observations at both time points.
What can a one-group study establish?
A single-arm before-and-after design can describe changes observed among participants who receive the intervention. Without a comparable control group, it cannot by itself distinguish a treatment-related change from changes over time, measurement variability, or other influences. The groups in this record are defined by participant or donor eligibility characteristics; the registry explicitly cautions that they are not a like-for-like control comparison. The nonrandomized design also means that treatment assignment was not randomized. These features limit causal interpretation, even if detailed outcome estimates are available.
The record’s study model is listed as parallel, while its design is also described as single-arm. The two group descriptions are not enough to infer a randomized or controlled comparison. The exact regimen mapping across the groups is not reported in the registry record. Statistical interpretation should therefore follow the explicit design description and avoid treating the group labels as evidence of comparative treatment allocation.
How should planning illustrations be read?
The record describes planning calculations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These assumptions describe a planning illustration, not the design actually used in this single-arm, nonrandomized study. The effect to detect is framed as a stated fraction of the observed effect. For time-to-event calculations, the planning quantity is total events; other planning quantities are participants per arm. The numerical planning estimates are not reported in the registry record.
Such calculations ask what sample size might be needed under specified assumptions to detect a target effect. They are not observed power, and they do not show that a study with its actual enrollment had a particular probability of detecting an effect. Because the assumptions include equal allocation between two arms, they do not describe the actual single-arm design. A sample-size illustration also depends on the effect used as its reference; if that effect estimate is uncertain, the resulting planning figure is uncertain as well. No protocol-based sample-size justification is reported in the registry record.
Finally, statistical significance and practical importance are different concepts. A test result, if available, would address compatibility with a specified statistical model and null hypothesis. It would not by itself establish the size, precision, or clinical meaning of a change. Here, the primary endpoint’s observed values, uncertainty estimates, and analysis results are not reported in the registry record, so those distinctions cannot be evaluated using trial results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several outcome domains: viral resistance, changes in CD4+ cell, lipid profile, renal function, and safety assessed through adverse events and serious adverse events. It also identifies a primary cyclosporine A pharmacokinetic endpoint. When a study examines multiple outcomes or multiple analyses, the chance of obtaining at least one apparently notable result can increase. Statistical methods may address this through prespecified outcome hierarchies, adjusted significance thresholds, or other approaches. Which, if any, approach was used is not reported in the registry record.
The record lists 8 outcome measures and 0 analysis records. It does not report whether all outcomes were analyzed, whether analyses were prespecified, how repeated measurements or multiple pharmacokinetic parameters were handled, or whether any adjustment for multiplicity was applied. The primary outcome names both Cmax and Cmin, but the record does not explain how they were combined or interpreted as a family of endpoints. No outcome-specific estimates or inferential results are available to clarify these decisions.
Missing-data handling is also not reported in the registry record. The enrollment figure does not establish how many participants had complete measurements at each time point, whether any participants discontinued, or how unavailable observations were treated. The analysis population is not described, and no intention-to-treat, per-protocol, or other population definition is reported. These omissions limit assessment of whether the analyzed participants represent everyone enrolled and how missing observations might affect the findings. They should not be filled in by assuming a conventional approach.
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 |
|---|---|---|---|
| DTG + 2 NRTIs | 1 | 19 | 5.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DTG + 2 NRTIs | 0 of 19 |
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 |
|---|---|
| DTG + 2 NRTIs | 15 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | DTG + 2 NRTIs |
|---|---|---|
| Cytomegalovirus infection | Infections and infestations | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DTG + 2 NRTIs |
|---|---|---|
| Other | General disorders | 10 of 19 |
| Diarrhea | Gastrointestinal disorders | 3 of 19 |
| Insomnia | Nervous system disorders | 1 of 19 |
| Tremor | Nervous system disorders | 1 of 19 |
| Anxiety symptoms | Nervous system disorders | 1 of 19 |
| Hyperglycemia | Endocrine disorders | 1 of 19 |
Serious events with the highest arm-level rate: cytomegalovirus infection (5.3%).
The registry reports 19 participants at risk for serious adverse events, with 1 affected participant, and 0 deaths. For other adverse events, it reports 19 at risk and 15 affected participants. These are participant-level figures as listed in the safety record; they should not be interpreted as counts of total event episodes. A participant may experience more than one event, but the record does not provide the event-level count or detail needed to describe that possibility.
Cytomegalovirus infection is listed among serious adverse-event terms with 5.3%. The registry does not provide enough detail to determine the number of episodes, timing, recurrence, or attribution for this term. The percentage should be read as reported, not recalculated from the participant counts. The record does not report a comparison group suitable for estimating a relative safety difference, and it does not provide a detailed account of how events were collected or classified. These figures describe reported safety observations; they do not establish whether an event was caused by a study drug.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed pilot study enrolled 19 people with HIV-1 infection and a solid organ transplant, and that its primary pharmacokinetic question concerned cyclosporine A Cmax and Cmin around a treatment switch. It also documents a dolutegravir-based treatment aim and lists safety and other secondary outcome domains. The reported safety figures include 1 participant affected by a serious adverse event among 19 at risk, 15 affected by other adverse events among 19 at risk, and 0 deaths. Cytomegalovirus infection is listed as a serious-event term with 5.3%.
These registry entries do not establish the magnitude or direction of the primary pharmacokinetic change. The observed Cmax and Cmin values, their dispersion, and an estimate of change are not reported in the registry record. Nor are numerical results for the listed secondary outcomes. Without outcome estimates and measures of uncertainty, readers cannot assess how precisely the pharmacokinetic question was answered or how compatible the observations are with different possible changes.
The design also defines what the evidence can address. The study is nonrandomized and described as single-arm. Its two group descriptions reflect eligibility characteristics, not a like-for-like control comparison. The record therefore does not provide a randomized contrast that could isolate treatment differences between groups. The broad stated aim includes safety and efficacy, but an aim is not a result, and the endpoint descriptions alone do not establish efficacy.
Nothing in the posted information supports a recommendation for an individual or a conclusion about treatment choice. Statistically, the most defensible reading is descriptive: the registry records the study’s design, intended measurements, enrollment, and selected safety counts, while leaving the primary outcome estimates and analysis details unreported. The study can be understood as an exploratory contribution to a pharmacokinetic question, but the record does not allow a quantitative conclusion about that question.
13. Why This Trial Matters Statistically
This study addresses a measurement problem in a population defined by both HIV-1 infection and solid organ transplantation. Its stated aim focuses on pharmacokinetic interactions between dolutegravir and immunosuppressant drugs, while the primary endpoint specifically names cyclosporine A. That focus makes the distinction between an intended measurement and an observed treatment effect especially important: pharmacokinetic data can describe concentrations, but the registry record does not report the values needed to characterize the observed change.
Statistically, the design highlights the limits of interpreting before-and-after observations without a randomized control group. A change measured around a switch may be useful for describing what happened in the enrolled participants, yet a single-arm design cannot separate a treatment-associated change from other changes over time. The eligibility-defined groups do not solve that problem because the registry states that they are not a like-for-like control comparison.
The study is also a reminder that small pilot trials can have an exploratory role without supplying precise or comparative estimates. Enrollment was 19, and the endpoint-specific analyzed population is not reported. The intended outcome definitions and the listed safety counts are informative about the questions under study, but the missing primary results prevent assessment of the size and precision of the pharmacokinetic findings. Clear reporting of estimates, uncertainty, analysis populations, missing data, and multiplicity would be necessary to evaluate those findings fully.
Finally, planning calculations should be distinguished from evidence generated by the actual design. The registry describes sample-size illustrations under equal allocation between two arms, whereas the study is characterized as single-arm and nonrandomized. Such illustrations can support hypothetical planning, but do not describe the trial’s observed power or turn its groups into a controlled comparison. This distinction matters when interpreting numerical planning outputs alongside a completed pilot study.
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 for interpreting the results is that the registry record does not report the observed primary endpoint data. Although it defines Cmax and Cmin, the units, summary statistics, and measurement timing, it gives no numerical endpoint values or estimate of change. Consequently, neither the direction nor precision of the pharmacokinetic findings can be assessed from the record.
The study enrolled 19 participants and is described as a nonrandomized, single-arm pilot. There is no like-for-like control comparison, and the group descriptions are based on eligibility characteristics. This limits causal interpretation and makes it inappropriate to treat the groups as randomized treatment arms. The record lists several possible drugs but does not specify the exact regimen received by each participant.
Other limitations arise from incomplete reporting. The endpoint-specific analysis population, missing-data methods, outcome analysis methods, multiplicity handling, and protocol-based sample-size justification are not reported in the registry record. The record lists 8 outcome measures but 0 analysis records, leaving the reported outcome summaries and inferential procedures unavailable. For safety, participant counts and a serious-event term are listed, but event-level detail, timing, and attribution are not reported.
These are limitations of what can be interpreted from the registry record; they do not establish that unreported analyses were not conducted. They do mean that readers cannot evaluate the robustness of the primary endpoint result, the extent of missing observations, or the evidence across the secondary outcomes from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients — NCT03360682.
- Registry record last updated 2025-09-30; status last verified 2025-09.
- Results first posted 2025-09-30.
- 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
NCT03360682 is a completed Phase 4, nonrandomized pilot study sponsored by Fundacion Clinic per a la Recerca Biomédica. The record lists 19 enrolled participants with HIV-1 infection who had received a solid organ transplant. It describes a dolutegravir-based regimen with two nucleoside reverse transcriptase inhibitors and a treatment period of 48 weeks.
The primary outcome is the change in cyclosporine A Cmax and Cmin, summarized by median and inter-quartile range in ng/mL. Measurements were specified 24-hours before the switch and 24-hours 2 weeks after switching. Observed primary endpoint results and analysis details are not reported in the registry record. Listed secondary domains include viral resistance, CD4+ cell changes, lipid profile, renal function, and adverse events.
The safety record lists 1 serious-event-affected participant among 19 at risk, 15 participants affected by other events among 19 at risk, 0 deaths, and Cytomegalovirus infection at 5.3%. The record does not provide a randomized control comparison or analysis records.