Targeting HIV Retention and Improved Viral Load Through Engagement ('THRIVE'): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeting HIV Retention and Improved Viral Load Through Engagement ('THRIVE') (NCT04481373), a randomized na study. The primary outcome is Acceptability of Enrollment and Randomization: Eligible But Declined Participation.

2. Clinical Question

The registry frames THRIVE as an intervention to improve engagement in outpatient HIV care after discharge. The posted primary outcome, however, focuses on enrollment and randomization acceptability through the number of eligible people who declined, rather than directly measuring subsequent engagement. The secondary outcomes address clinical and care-engagement measures, but their results should be read as separate outcomes rather than as substitutes for the primary measure.

3. Trial Design

The registry describes a randomized, single-masked, parallel-group trial of THRIVE compared with Treatment as Usual. Enrollment was 75, and the record lists the trial status as completed. The recorded start date is 2021-03-03 and the primary completion date is 2024-02-29. Phase is listed as NA. Further information on who was masked is not reported in the registry record.

The THRIVE arm included 39 participants and the Treatment as Usual arm included 36. These are the arm sizes recorded for the primary outcome; the secondary outcomes have different outcome-specific denominators. The registry does not report why those denominators differ, so the difference should not be assigned to missing observations, eligibility changes, or any other cause without further information.

THRIVE combined Acceptance and Commitment Therapy with HIV education. It was intended for hospitalized people with HIV who were out of care and endorsed avoidance. Treatment as Usual involved usual hospital care, with service linkage workers meeting hospitalized people with HIV and covering educational aspects of care. The registry description of the THRIVE intervention is truncated, so additional details about its content are not reported in the registry record.

The primary outcome was acceptability of enrollment and randomization, operationalized as the count of eligible people who declined participation over 6 months. The posted secondary outcomes were viral load improvement and the number of patients retained in HIV care, both with a 6-month timeframe. The registry lists 13 outcome measures overall, but only two secondary outcomes are described in the posted results summarized in these results. The statistical analysis plan, sample-size justification, interim analyses, and details of outcome assessment are not reported 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

Reasons for not completing this period:

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 Acceptability of Enrollment and Randomization: Eligible But Declined Participation, measured over 6 months.

The primary outcome is titled “Acceptability of Enrollment and Randomization: Eligible But Declined Participation.” Its stated measure is the number of eligible people with HIV who agree and decline to participate, and the reasons for declining, over 6 months. The posted results report a count of zero for THRIVE and zero for Treatment as Usual. The outcome description includes reasons for declining, but reasons are not reported in the registry record.

This measure is used to assess whether eligible people are willing to join a study and accept random assignment. In general, enrollment and randomization acceptability can inform whether a proposed approach is feasible to test in a future study. It is different from an outcome measuring whether participants remain in care or experience a change in viral load. Those questions are addressed separately by the posted secondary outcomes.

The record does not explain how the primary outcome was linked to the randomized arm denominators, or whether the counts refer to people approached before randomization or a different population. That detail matters because a decline in participation is conceptually distinct from an outcome observed among randomized participants. The reported zero counts therefore describe what the registry posted, but the precise population and counting process are not reported in the registry record.

7. Results Posted in the Registry

• THRIVE: 0.0% (0/39) versus 0.0% (0/36) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Viral Load Improvement

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • THRIVE: 38.7% (12/31) versus 43.8% (14/32) on control; risk difference -5.0 percentage points (95% CI -29.3 to 19.2), risk ratio 0.88 (0.49–1.60); unadjusted two-proportion z-test p = 0.685.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between THRIVE and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients Who Are Retained in HIV Care

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • THRIVE: 39.4% (13/33) versus 50.0% (16/32) on control; risk difference -10.6 percentage points (95% CI -34.6 to 13.4), risk ratio 0.79 (0.46–1.36); unadjusted two-proportion z-test p = 0.390.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between THRIVE and the control. The interval gives the range of effects that remain compatible with the data.

Across the two posted secondary outcomes, the point estimates are below zero for the THRIVE-versus-Treatment-as-Usual risk differences. Both confidence intervals include zero and extend to values on either side. The overall pattern is therefore one of uncertain comparisons, rather than clear evidence of a consistent difference across outcomes. The relative measures likewise have intervals spanning their no-difference value.

These secondary measures address the aims described for the intervention more directly than the primary outcome of eligible people declining participation: viral load improvement and remaining in HIV care relate to the stated goals of improving viral load and outpatient care engagement. They do not, however, resolve questions about the primary endpoint's meaning or establish an effect on the broader goals described in the registry. Each outcome has its own denominator, and reasons for the differing denominators are not reported in the registry record.

The secondary p-values are unadjusted. In general, when several outcomes are examined, the chance of obtaining at least one seemingly notable result can increase if no allowance is made for multiple comparisons. Adjustment procedures and a prespecified hierarchy of outcomes are not reported in the registry record. The unadjusted results therefore warrant less weight than a clearly specified primary analysis, particularly when the analysis plan and handling of missing observations are not documented in the record.

The registry lists 13 outcome measures but reports results for two secondary outcomes in the posted data. The status of other outcome measures and reasons results are not available are not reported in the registry record. The secondary findings are best treated as exploratory descriptive evidence that can inform questions for later research, not as definitive confirmation or disconfirmation of the intervention's aims.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Viral Load Improvement
• Number of Patients Who Are Retained in HIV Care

9. Statistical Interpretation

10. Statistical Methods Explained

In general, a randomized parallel-group design assigns participants to one of the study arms and compares outcomes between those groups. Randomization is intended to reduce systematic differences at assignment, but it does not guarantee that every later outcome is measured for every participant or that the groups remain comparable in all respects. The registry identifies this trial as randomized and parallel, but further details on the randomization procedure and masking are not reported in the registry record.

What does a risk difference mean?

In general, a risk difference subtracts the outcome proportion in the comparator group from the outcome proportion in the intervention group. A value below zero means the recorded outcome proportion was lower in the intervention group; a value above zero means it was higher. For viral load improvement the posted risk difference is -0.050, and for retention it is -0.106. These are unadjusted comparisons from the posted counts, not evidence that assignment caused a change. The confidence intervals indicate substantial uncertainty about the underlying differences.

How do relative measures differ?

In general, a risk ratio compares outcome proportions by division, while an odds ratio compares the odds of the outcome between groups. A value of 1 is the no-difference value for either measure. The posted risk ratios and odds ratios are accompanied by confidence intervals that include 1 for both secondary outcomes. This means the data are compatible with no relative difference as well as with differences in either direction. Relative measures can be less intuitive than risk differences, so they should be interpreted alongside the outcome counts and absolute comparison.

What does a confidence interval communicate?

In general, a confidence interval reflects statistical uncertainty around an estimate under the assumptions of the method used. A wider interval indicates less precision. An interval that includes the no-difference value does not prove that the groups are identical; it means the observed data do not rule out that value at the interval's stated confidence level. The registry does not report the confidence-interval construction method or a detailed statistical analysis plan.

How should p-values be read?

In general, a p-value measures how unusual results at least as extreme as those observed would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, nor a measure of the size or importance of an effect. The unadjusted p-values are 0.685 for viral load improvement and 0.39 for retention. They are not adjusted for multiple secondary comparisons, and no sponsor-reported analyses are listed in the registry record. The method used to derive these p-values is not reported in the registry record.

What do the planning illustrations mean?

The posted planning illustrations are based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are not the trial's design justification and are not observed power. For viral load improvement, planning for 100% of the observed effect gives 1,497 participants per arm for 80% power and 2,003 participants per arm for 90% power. Planning for 75% of the observed effect gives 2,673 participants per arm for 80% power and 3,577 participants per arm for 90% power. Planning for 50% of the observed effect gives 6,039 participants per arm for 80% power and 8,084 participants per arm for 90% power.

For retention, planning for 100% of the observed effect gives 344 participants per arm for 80% power and 460 participants per arm for 90% power. Planning for 75% of the observed effect gives 616 participants per arm for 80% power and 823 participants per arm for 90% power. Planning for 50% of the observed effect gives 1,391 participants per arm for 80% power and 1,861 participants per arm for 90% power. These illustrations depend on the observed effect, which is uncertain, and should not be read as evidence that the trial had a particular power or that a future study should use these sizes. The trial's own sample-size assumptions are not reported in the registry record.

11. Confidence Intervals and Precision

The secondary estimates are imprecise. The confidence interval for the viral load improvement risk difference extends from -0.293 to 0.192 around the estimate of -0.050. The interval includes zero and allows for effects in either direction. The retention risk difference is -0.106, with an interval from -0.346 to 0.134, which also includes zero and covers effects in either direction. These intervals do not support a precise conclusion about the size or direction of the underlying differences.

In general, a confidence interval describes a range of values compatible with the observed data and the statistical method's assumptions. It is not a guarantee that the true effect lies within that particular interval, and it does not show the probability that any one value is correct. Its width is especially relevant for these results: the ranges are broad relative to the point estimates, leaving substantial uncertainty.

The relative-effect intervals reinforce that interpretation. For viral load improvement, the risk ratio interval is 0.489 to 1.599 and the odds ratio interval is 0.297 to 2.218. For retention, the risk ratio interval is 0.456 to 1.361 and the odds ratio interval is 0.243 to 1.738. Each interval includes the no-difference value for its measure. The point estimates alone should not be treated as precise estimates of a treatment effect.

The primary outcome is different: its posted risk difference and interval are all 0.0. A collapsed interval can appear to convey complete precision, but the record does not describe how this estimate was calculated or clarify the relationship between the eligible people who declined and the randomized-arm denominators. The zero result should therefore be understood as the posted count and comparison, not as evidence that uncertainty about acceptability is absent. The registry does not report a p-value for this primary comparison.

12. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a prespecified hierarchy for outcomes, or an approach to multiplicity. It lists 13 outcome measures and posts results for two secondary outcomes. The associated p-values are unadjusted. In general, testing multiple outcomes without accounting for multiplicity can make isolated small p-values less persuasive, because the opportunity for chance findings grows as more comparisons are considered. The posted secondary p-values are not evidence of an adjusted confirmatory analysis.

The record lists zero sponsor-reported analyses. The method used for the posted risk differences, confidence intervals, and p-values is not reported in the registry record. Interim analyses are also not reported in the registry record. These omissions limit assessment of whether the posted calculations followed a prespecified plan and how the results should be weighted relative to other outcomes.

Missing-data handling is not reported in the registry record. The secondary outcome denominators differ between arms and between outcomes. The record does not state whether this reflects missing outcome information, availability of measurements, eligibility, or another reason. It is therefore not possible to determine from these results alone whether the comparisons include all randomized participants or whether missingness could have affected them. No imputation method, sensitivity analysis, or analysis population definition is reported.

The primary outcome description refers to eligible people who agreed or declined, while the posted results give arm-level counts among the randomized groups. How these populations and denominators are connected is not reported in the registry record. That uncertainty is especially important when interpreting the zero counts and the risk difference interval of 0.0 to 0.0. Additional registry entries or a full report would be needed to clarify the outcome definitions, analysis populations, missing-data approach, and multiplicity strategy.

13. 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.

For THRIVE, the registry reports 0 serious adverse events among 35 at risk and 0 other adverse events among 35 at risk. For Treatment as Usual, it reports 0 serious adverse events among 35 at risk and 0 other adverse events among 35 at risk. The record also reports 2 deaths in THRIVE and 1 in Treatment as Usual.

These figures should be read as counts recorded in the registry, not as evidence about the cause of any death or whether an event was related to an intervention. The registry information does not report attribution, timing, narratives, or further detail about the deaths. The serious-event counts are zero in both groups, but that does not establish that no other safety concerns occurred outside the recorded categories or observation period. The registry record does not provide additional context for interpreting the at-risk counts or explain their relationship to the arm sizes reported for the primary outcome.

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

The posted results describe a completed randomized pilot trial of THRIVE compared with Treatment as Usual. The primary endpoint records zero eligible people declining participation in both arms, while the two secondary outcomes have risk-difference estimates below zero and confidence intervals that include zero. The secondary intervals are broad, and the primary outcome's calculation and population are not sufficiently explained in the registry record to support a strong inference from its collapsed interval.

These results do not establish that THRIVE improved viral load or retention in HIV care, and they do not establish that it had no effect. The posted secondary estimates are compatible with a range of possible differences, and the record does not document an analysis plan or missing-data handling that would support stronger claims. Likewise, the primary count alone cannot establish that the study approach would be acceptable across other settings or populations.

In general, a pilot study can produce information about feasibility, outcome measurement, and the range of results that might inform later research. The registry describes THRIVE as an intervention to be developed and pilot tested, with larger-scale testing contemplated in later studies if development is successful. The planning illustrations are based on observed effects and are not observed power or the trial's own sample-size justification.

The appropriate statistical reading is consequently cautious: the record provides descriptive counts and unadjusted comparisons, but substantial uncertainty remains about the secondary effects and important analytic details are not reported. No conclusion about individual care or treatment choice follows from these registry results.

15. Why This Trial Matters Statistically

This trial raises an important design distinction between whether eligible people will enroll in a study and whether an intervention changes later outcomes. The primary endpoint addresses acceptability of enrollment and randomization, while viral load improvement and retention in HIV care are separate secondary measures. Keeping these questions distinct helps readers understand what each result can and cannot answer.

The posted secondary estimates also illustrate why point estimates should be interpreted with their confidence intervals. A negative estimate alone may appear to suggest a direction, but intervals that include zero and span values in both directions leave considerable uncertainty. Unadjusted p-values do not resolve that uncertainty, especially when the registry lists multiple outcomes and does not report a prespecified analysis strategy.

The record is also a reminder that denominators and outcome definitions are central to interpretation. The outcome-specific denominators differ, and the relationship between the primary endpoint's eligible population and randomized arms is not explained. Missing-data methods and analysis populations are not reported. Without those details, readers cannot assess whether the posted comparisons answer the intended questions in a consistent way.

Finally, the sample-size illustrations are planning aids built from observed effects, not evidence about the power of this completed trial. Their values depend on uncertain estimates. In statistical terms, the most useful contribution of these results is to identify questions and uncertainties for future evaluation, rather than to provide a definitive estimate of intervention effect.

16. 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 registry record affect interpretation. The primary outcome is described as the number of eligible people who agree and decline, but its posted results are zero for both randomized arms. The record does not explain the population used to calculate those counts, the reasons for declining, or how this outcome relates to the randomized participants. The reported risk difference interval of 0.0 to 0.0 is not accompanied by a description of its calculation.

For the secondary outcomes, the registry reports different denominators across outcomes and arms. It does not explain why those denominators differ, how missing outcomes were handled, or which analysis population was used. The statistical methods for the estimates and unadjusted p-values are not described, and no sponsor-reported analyses are listed. The record also does not state whether outcome definitions or analyses were prespecified.

The registry lists 13 outcome measures but posts two secondary results in the available results. It does not explain the status of the other outcome measures. The THRIVE arm description is truncated, and further intervention details are not reported in the registry record. The masking target, randomization procedures, and sample-size justification are also not reported.

Finally, the secondary confidence intervals are broad, so the estimates are imprecise. The planning illustrations use observed effects and cannot resolve this uncertainty or substitute for a design rationale. Safety results are limited to the recorded event counts, at-risk counts, and deaths, without attribution or further clinical detail. These limitations mean the registry results offer an incomplete basis for judging the size, precision, and robustness of any intervention effect.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Targeting HIV Retention and Improved Viral Load Through Engagement ('THRIVE') — NCT04481373.
• Registry record last updated 2025-10-14; status last verified 2025-09.
• Results first posted 2025-10-14.
• 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.

20. Record Summary

NCT04481373 is a completed randomized, single-masked, parallel-group trial comparing THRIVE with Treatment as Usual. Enrollment was 75. The recorded start date is 2021-03-03, and the primary completion date is 2024-02-29. Phase is listed as NA.

The primary outcome assessed eligible people who declined participation over 6 months; the posted count is zero in each arm. The secondary outcomes were viral load improvement and retention in HIV care over 6 months. Their posted risk differences are -0.050 and -0.106, respectively, and both confidence intervals include zero. Sponsor-reported analyses are not listed. The registry does not report the analysis plan, missing-data approach, or sample-size justification.

The registry identifies Baylor College of Medicine as sponsor and lists HIV, depression, and anxiety as conditions. Safety results include zero reported serious adverse events in each group and deaths recorded in both groups; attribution is not reported in the registry record.