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 Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART (NCT01869634), a non-randomized phase 4 study. The primary outcome is Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01869634 |
| Phase | Phase 4 |
| Condition | Human Immunodeficiency Virus Infection |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 37 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, Davis |
| Results posted | Yes |
2. Clinical Question
Population
People with HIV who were naive to antiretroviral therapy (ART) were studied alongside age-matched HIV-negative control volunteers. The registry record lists enrollment of 37. The HIV-negative participants underwent study procedures without receiving ART.
Intervention
The HIV group received open-label darunavir 800 mg with ritonavir 100 mg and fixed-dose tenofovir disoproxil fumarate plus emtricitabine (Viread plus emtricitabine, identified as Truvada®), taken once daily. The registry describes this as darunavir-based ART.
Comparator
The primary endpoint description refers to age-matched HIV-negative control volunteers. They did not receive ART. The study was non-randomized, so these volunteers were not assigned as a randomized treatment control group. The registry describes a within-person before-and-after comparison for the HIV group.
Primary question
How did the number of CD4+ T-cells per mm2 in the lamina propria change between baseline and 12 months of therapy in the HIV group, and how did these measurements compare with those in age-matched HIV-negative volunteers? The registry names the endpoint but does not report its numerical results.
The study’s stated rationale was to examine whether potent HIV suppression with darunavir-based ART would be associated with repopulation of gastrointestinal-associated lymphoid tissue CD4+ T-cell populations, normalization of systemic immune activation, and improved HIV-associated cardiovascular disease risk. These are aims described in the registry summary, not findings established by the endpoint information available in the registry record. The primary endpoint focuses on CD4+ T-cell density in the lamina propria, a tissue measure rather than a blood count. The registry also lists change in percentage of total artery diameter as a secondary outcome, but does not provide its numerical result.
3. Trial Design
The registry identifies this as a completed Phase 4, parallel, non-randomized study with no masking. Enrollment is listed as 37. The study began in 2013-06, and primary completion is listed as 2016-12. The sponsor is University of California, Davis. The condition listed is human immunodeficiency virus infection.
The study included an HIV-positive group described as naive to ART and a group of normal control volunteers who were HIV-negative and age-matched. The HIV-positive participants received open-label darunavir with ritonavir and fixed-dose Viread plus emtricitabine. The control volunteers did not receive ART. Because allocation was non-randomized, the control group should not be interpreted as a like-for-like randomized treatment comparison. Differences between groups could reflect factors other than HIV status or treatment, and the registry does not report an adjustment strategy to address such differences.
The design includes a before-and-after assessment in the HIV group. The primary endpoint description specifies baseline and 12 months, and the registry says that the within-person comparison used a Wilcoxon signed-rank test. HIV-negative participants are described in the primary endpoint population text as undergoing procedures once at screening. However, the control-arm description says that controls underwent the same procedures at study entry and after 12 months. This inconsistency in timing is not resolved in the registry record.
The HIV-positive arm description mentions upper endoscopy and cardiovascular procedures, including CT cardiac angiogram and intimal-medial thickening assessment. The description is truncated after “and p”, so the full list of procedures is not reported in the registry record. The study’s status is completed, but completion status alone does not establish that every planned measurement was obtained or reported.
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 Positive Naive to ART | Normal Control Volunteers |
|---|---|---|
| STARTED | 20 | 17 |
| COMPLETED | 18 | 17 |
| NOT COMPLETED | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: HIV negative participants underwent the procedures only once at Screening (entry). In the HIV group the comparison between before and after ART was done using a Wilcoxon signed-rank test.
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 Positive Naive to ART | Normal Control Volunteers | Total |
|---|---|---|---|---|
| Participants analysed | 18 | 17 | 35 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 18 | 17 | 35 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 40 (31 to 51) | 37 (33 to 47) | 37 (32 to 50) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 18 | 17 | 35 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 4 | 2 | 6 |
| Race (NIH/OMB): White | Participants | 7 | 8 | 15 |
| Race (NIH/OMB): More than one race | Participants | 5 | 6 | 11 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 18 | 17 | 35 |
| CD4+ T-cells | cells/mm^3 | 215 (150 to 260) | 460 (370 to 530) | 310 (210 to 460) |
| HIV viral load | copies/ml | 41032 (20689 to 78805) | 0 (0 to 0) | 41032 (20689 to 78805) |
| weight | lbs | 187 (153 to 200) | 194 (176 to 210) | 191 (170 to 210) |
6. Primary Endpoint
The registry lists the primary outcome as Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV, measured over Baseline, 12 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | cells / mm^2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of CD4+ T-cells in the lamina propria per mm2, measured at baseline and 12 months in the HIV group and considered in relation to age-matched HIV-negative control volunteers. The registry specifies that the endpoint is summarized using a median and inter-quartile range. Numerical median values, inter-quartile ranges, and an estimated change are not reported in the registry record.
In general, a tissue cell-density measure describes how many cells of a specified type are present within a defined area of tissue. CD4+ T-cells are relevant to the study’s stated focus on immune reconstitution in gastrointestinal-associated lymphoid tissue. Measuring them in the lamina propria provides information about a tissue compartment, rather than relying only on circulating blood measurements. This helps define what biological feature the endpoint is intended to assess; it does not, by itself, establish the clinical importance of any observed change.
The endpoint is framed around change over time in the HIV group and comparison with HIV-negative volunteers. The registry identifies a paired, within-person test for the HIV group. It does not specify a statistical test for a between-group comparison, nor does it report whether the control measurements were used in a formal inferential analysis. Accordingly, the endpoint’s stated purpose can be described, but the magnitude, precision, and statistical evidence for a treatment-associated change cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, design, endpoint definition, and the named test for the within-person analysis. It does not include the primary endpoint’s observed median values, inter-quartile ranges, estimated change, confidence interval, or p-value. It is therefore not possible to describe the direction or size of the CD4+ T-cell change from the registry information available in this record. The study’s stated expectations about immune reconstitution, systemic immune activation, and cardiovascular risk are objectives, not reported results.
The study is non-randomized and unmasked. The HIV-positive participants received ART, while HIV-negative volunteers served as age-matched controls without ART. This arrangement can describe measurements in these groups, but it does not isolate a causal treatment effect in the way a randomized comparison is intended to do. The groups differ by HIV status as well as treatment exposure, and the registry does not report a method for adjusting for possible differences. A comparison between them therefore needs to be interpreted as observational.
The within-person comparison in the HIV group addresses change from baseline to 12 months. The registry names a Wilcoxon signed-rank test for this analysis, but does not report its test statistic, p-value, or an effect estimate with uncertainty. Without those results, statistical compatibility with no change cannot be assessed. Nor can the precision of the estimate be judged. A median and inter-quartile range describe the distribution, but the registry record contains no values for either.
The age-matched control group may provide context for the tissue measurements, but the record is inconsistent about whether controls underwent procedures only at screening or also after 12 months. The primary endpoint population description says screening only; the arm description says entry and after 12 months. This matters when interpreting whether the endpoint comparison is cross-sectional, longitudinal in both groups, or a combination. The available description does not resolve that issue.
There is also no reported account of missing endpoint measurements, the number of participants included in each analysis, or how missing observations were handled. These details affect how far the analyzed observations represent the enrolled groups. The registry’s enrollment and adverse-event at-risk figures do not substitute for endpoint-specific analysis counts.
Overall, the record supports a careful description of the research question and analysis method, but not a conclusion about the observed endpoint. The registry record does not report whether the primary endpoint increased, decreased, or remained similar, and does not report the size or precision of any change. Any interpretation of treatment effects, differences from controls, or clinical relevance would go beyond the reported results.
9. Statistical Methods Explained
The primary endpoint is expressed as a median with an inter-quartile range. In general, the median is the midpoint of ordered observations, while the inter-quartile range describes the spread of the central portion of the observed values. These summaries can be useful when a distribution is skewed or includes values that make a mean less representative of a typical observation. The registry does not report the actual median or inter-quartile range for this endpoint, so the distribution and its spread cannot be assessed.
What does the Wilcoxon signed-rank test assess?
The registry says that the comparison before and after ART in the HIV group used a Wilcoxon signed-rank test. In general, this is a paired-data method: it considers the within-person differences between two measurements and evaluates whether those differences are centered around no change under the test’s assumptions. It does not treat the two measurements from the same participant as independent observations. Its use is consistent with a before-and-after question in which each participant can contribute a baseline and follow-up value.
The test result alone would not describe the size of a change. An effect estimate and an interval describing its uncertainty would be needed to show the estimated magnitude and precision. The registry record does not report the test statistic, p-value, confidence interval, or numerical endpoint summaries. Consequently, the method can be identified, but its result cannot be independently interpreted from this record.
How should the control group be understood?
The controls were HIV-negative, age-matched volunteers and did not receive ART. They were not a randomized treatment group, and the trial allocation is explicitly non-randomized. In general, matching on age can make groups more comparable with respect to age, but it does not ensure comparability on other measured or unmeasured characteristics. The registry does not report a matching procedure beyond describing controls as age-matched, or an adjusted model for the endpoint.
The primary endpoint title refers to comparison with age-matched controls, while the population description specifies the Wilcoxon signed-rank test for the before-and-after comparison in the HIV group. No method for a formal comparison between the HIV group and controls is reported. Thus, the control group’s role in the inferential analysis is not fully described. The timing description also differs: the primary endpoint text says HIV-negative participants underwent procedures only at screening, while the arm description says controls underwent procedures at entry and after 12 months. That inconsistency limits clarity about which measurements support the endpoint comparison.
What does non-randomized allocation imply?
In general, random allocation helps balance both known and unknown prognostic factors across treatment groups. Here, participants with HIV received ART and HIV-negative controls did not, so treatment exposure is inseparable from group status in a direct between-group comparison. The study can assess within-person change among treated participants, but changes over time can also reflect factors other than treatment. Without a randomized untreated HIV comparison group or a reported adjustment strategy, a before-and-after difference cannot be interpreted as an isolated causal effect of ART.
The study is unmasked. In general, lack of masking can influence some aspects of measurement or study conduct, depending on the outcome and procedures. The primary endpoint is a tissue cell count, but the record does not report who performed or assessed the measurements, whether laboratory staff were masked, or what quality-control procedures were used. No specific bias can be inferred from the missing information; these details are simply not reported in the registry record.
How should planning illustrations be read?
The registry describes sample-size assumptions as a planning illustration calculated from the observed effect, not as the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event tables, the record says totals of events are used; other illustrations are expressed as participants per arm. These are planning assumptions, not a report of the study’s actual design justification.
In general, a sample-size calculation estimates how much information a future study might need under a specified statistical model and assumed effect. It is conditional on the assumptions used, including the effect size and analysis approach. An illustration based on an observed effect is not evidence that the completed trial had a particular probability of detecting an effect. It is not observed power and does not replace an estimate with a confidence interval. The registry does not report the trial’s own sample-size justification, so that rationale is not reported in the registry record.
The record does not report the full statistical analysis plan, any interim analyses, or a prespecified approach to multiple outcomes. The five analyses listed in the record are not accompanied by enough detail to establish how they relate to the endpoint or which analysis was primary for inference. There are three outcome measures listed, but the numerical results and analysis populations are not reported in the endpoint information. These omissions prevent a broader assessment of analytic choices and multiplicity.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three outcome measures and five analyses, and identifies change in percentage of total artery diameter as a secondary outcome. It does not report a multiplicity adjustment or a hierarchy describing which outcomes or analyses should carry confirmatory weight. A statistical plan addressing multiplicity is not reported in the registry record.
In general, when several outcomes or analyses are tested, the chance of at least one apparently notable result can increase if each is interpreted separately without accounting for the number of comparisons. Methods for addressing this concern depend on the intended inferential goals. Because the registry does not state whether the analyses were exploratory or confirmatory, or how they were prioritized, the implications of multiple testing cannot be determined.
Missing-data information is also not reported in the registry record. The record does not provide endpoint-specific analysis counts, the amount or pattern of missing measurements, reasons for missingness, or a method for handling missing observations. It does not describe an imputation method or a sensitivity analysis. These omissions mean that the available endpoint population and the assumptions underlying any analysis cannot be evaluated.
The registry names the HIV-positive group as the population for the before-and-after Wilcoxon signed-rank test, but does not specify whether all enrolled participants with available measurements, a defined subset, or another analysis population was used. The control population description is also inconsistent about assessment timing. The trial’s full statistical analysis plan, interim analyses, and sample-size justification are 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 Positive Naive to ART | 0 | 18 | 0.0% |
| Normal Control Volunteers | 0 | 17 | 0.0% |
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 Positive Naive to ART | 0 of 18 |
| Normal Control Volunteers | 0 of 17 |
The registry lists adverse-event figures separately for the HIV-positive group naive to ART and normal control volunteers. For the HIV-positive group, 18 were listed as at risk for serious adverse events and 0 as affected; 18 were listed as at risk for other adverse events and 0 as affected. For normal control volunteers, 17 were listed as at risk for serious adverse events and 0 as affected; 17 were listed as at risk for other adverse events and 0 as affected. The registry lists no serious adverse-event terms.
These figures indicate that no affected participants were recorded in the listed serious or other adverse-event categories. They do not establish that no symptoms or events occurred outside the registry’s reported categories, nor do they describe event severity, duration, timing, or relationship to treatment. Death counts are null for both groups, so deaths are not reported in the registry record; null should not be read as a reported zero.
In general, adverse-event counts depend on how events were defined, collected, and entered into the record. The registry does not provide those details here, nor does it report an adverse-event observation window. The at-risk counts are safety-reporting denominators and should not be treated as endpoint analysis counts. The record also does not provide enough information to compare safety between groups as a causal treatment effect, given the non-randomized design and the different HIV status and treatment exposure of the groups.
12. What the Result Does, and Does Not, Mean
This study asks a focused biological question: whether the density of CD4+ T-cells in the lamina propria changed from baseline to 12 months among people with HIV receiving darunavir-based ART, and how that measure related to values in age-matched HIV-negative volunteers. The registry provides the endpoint definition and identifies a paired test for the HIV-group comparison. It does not report the endpoint values or test result. The direction, magnitude, and precision of any change therefore cannot be stated from the registry record.
The stated objectives extend beyond the primary endpoint to systemic immune activation and HIV-associated cardiovascular disease risk. The brief summary describes anticipated effects, but an anticipated mechanism or benefit is not an observed result. The registry lists change in percentage of total artery diameter as a secondary outcome, but does not report a numerical finding for it. The record does not include results for systemic immune activation in the information available for this analysis.
Even if a before-and-after change were reported, the design would require cautious interpretation. The HIV-positive group received ART, while the age-matched comparison group was HIV-negative and untreated. The groups were not randomized, and the registry does not report adjustment for group differences. A change over time in the treated group could be associated with treatment, but the design as described cannot separate that association from all other possible causes.
In general, a statistical result and its clinical meaning are related but distinct. A test can address whether data are compatible with a particular statistical hypothesis, while clinical relevance depends on the size and context of the effect and the validity of the measurement. The registry record does not provide the numerical information needed to assess either the statistical evidence or the clinical importance of the primary endpoint.
The appropriate conclusion is limited: the study was designed to examine tissue immune reconstitution in relation to darunavir-based ART, using a before-and-after analysis in the HIV group and age-matched HIV-negative controls for context. Whether the observed data support the stated expectations is not reported in the registry record.
13. Why This Trial Matters Statistically
The study illustrates why the definition of an endpoint matters. CD4+ T-cell density in the lamina propria captures a tissue feature relevant to the stated focus on gastrointestinal-associated lymphoid tissue. It is distinct from a blood-based immune measure and answers a more specific biological question. Clear endpoint definitions help readers distinguish what a study measures from broader hypotheses about immune recovery or clinical outcomes.
It also demonstrates the importance of separating a within-person comparison from a between-group comparison. The registry identifies the Wilcoxon signed-rank test for baseline-to-follow-up measurements in the HIV group. The HIV-negative volunteers provide a potential reference context, but they are not a randomized untreated HIV group. Treating these comparisons as interchangeable would obscure the design’s limits.
The record further shows why results and methods need to be read together. Knowing the summary measure and named test does not reveal the effect’s size or precision. Without endpoint values, an estimate, and uncertainty information, the statistical evidence cannot be assessed. A stated objective is not a substitute for a reported result.
Finally, internal consistency in the description affects interpretation. The control assessment timing differs between the arm description and primary endpoint population text. Clarifying that timing, analysis populations, missing-data handling, and the role of controls would make the analytic path easier to evaluate. These are practical reporting issues: they determine what comparison was actually made and how confidently readers can understand it.
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 registry record does not report numerical results for the primary endpoint. Medians, inter-quartile ranges, a change estimate, an uncertainty interval, and a p-value are absent. It is therefore not possible to assess the observed endpoint effect or its precision. The test is named, but its output is not.
The non-randomized design is an important limitation for causal interpretation. The ART-treated participants had HIV, while the untreated controls were HIV-negative. These groups differ in both HIV status and treatment exposure, and the record does not describe an adjustment strategy. Age matching is mentioned, but the registry does not report details of how matching was conducted or whether other characteristics were considered.
The descriptions of control timing are inconsistent. The primary endpoint population text says HIV-negative participants underwent procedures only at screening, while the control-arm description says the same procedures occurred at entry and after 12 months. This makes it unclear whether the control contribution to the endpoint is based on entry values alone or includes follow-up values.
Other details relevant to interpretation are not reported in the registry record: endpoint-specific analysis counts, missing-data handling, reasons for missing observations, the full statistical analysis plan, a multiplicity approach, interim analyses, and the trial’s sample-size justification. The HIV-positive arm description is truncated, leaving the full procedure list unclear. The registry also does not report the numerical results for the listed secondary outcome. These gaps limit assessment of both analytic choices and the broader study objectives.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART — NCT01869634.
- Registry record last updated 2020-03-04; status last verified 2020-02.
- Results first posted 2020-03-04.
- 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
NCT01869634 is a completed Phase 4, non-randomized, unmasked, parallel study sponsored by University of California, Davis. It lists enrollment of 37 and examines darunavir-based ART in HIV-positive participants naive to ART, with age-matched HIV-negative control volunteers who did not receive ART. The primary endpoint is lamina propria CD4+ T-cell number per mm2 at baseline and 12 months. The registry specifies median and inter-quartile range summaries and a Wilcoxon signed-rank test for the before-and-after comparison in the HIV group.
The registry record does not report numerical primary endpoint results, uncertainty estimates, or a p-value. It also does not report the endpoint analysis population or missing-data handling. Control assessment timing is described inconsistently. The listed safety figures record zero affected for serious and other adverse events in each group; death counts are not reported. The study’s objectives should be distinguished from findings, which are not included in the registry record.