Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens (NCT03976752), a non-randomized phase 1 study. The primary outcome is Plasma Concentration of Tenofovir (TFV).

2. Clinical Question

3. Trial Design

This Phase 1 study was designed to describe antiretroviral drug concentrations across body sites and sampling times. Its stated focus was whether uptake of Genvoya at different time frames differs at several body sites, including mucosal tissues. The primary endpoint concerns plasma tenofovir concentrations; the registry also lists secondary outcomes for tenofovir-diphosphate and emtricitabine-triphosphate concentrations in peripheral blood mononuclear cells.

The study was non-randomized, unmasked, and described as sequential. Participants were assigned to specimen-collection schedules rather than randomized treatment groups. The Genvoya schedules involved collection 2 and 48 hours, 4 and 72 hours, or 24 and 96 hours after dosing, while a separate medication arm involved collection at 8 hours. The pre-drug arm received no medication and underwent specimen collection. The registry states that concentration analysis was not performed for this arm because no drugs were administered.

The registry reports enrollment of 41. It also notes that two participants were in multiple study arms. Consequently, arm-level descriptions cannot be interpreted as separate, non-overlapping participant groups. The record lists a start date of 2019-03-13, primary completion on 2019-09-20, and a completed status. These design features support a descriptive reading of the scheduled concentration measurements, not a randomized comparison of treatment effects.

The registry record does not report a statistical plan, a sample-size justification, or an inferential comparison between schedules. It lists 10 outcome measures and no analyses. The existence of multiple sampling schedules and outcomes does not by itself establish that formal hypothesis tests were planned or performed.

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: After the completion of enrollment in the Pre-drug arm, enrollment began sequentially in Arm A, followed by Arm B and Arm C. Arms A, B, and C were further broken down into two different sub-groups, determining the timing of the rectal swab and biopsy procedure. Arm D was enrolled last and included a single time point specimen collection. Participants were able to take part in more than one study arm, with at least a 6 week period after completion of one study arm before beginning another one.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data are reported per intervention, based on the time points of sample collection for each study arm (two participants were in multiple study arms). Analysis of drug concentrations in participants in the Pre-drug arm was not performed as no drugs were administered to this study arm.

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 Plasma Concentration of Tenofovir (TFV), measured over Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication.

The primary endpoint is median plasma concentration of tenofovir, reported in ng/mL. Tenofovir is identified in the registry as a component of Genvoya. The endpoint is defined at baseline and at 2, 4, 8, 24, 48, 72, and 96 hours after taking the second medication dose. The registry specifies full range as the dispersion measure accompanying the median.

Concentration measurements describe the amount of the drug component measured in plasma at a particular sampling time. Repeated time-specific measurements can characterize how concentrations vary over the scheduled follow-up period. This is relevant to a pharmacokinetic study because the stated research interest is drug uptake over time and across body sites. This general explanation describes the role of concentration measurements; it is not a claim about the observed pattern in this study.

The registry says concentrations below the limit of quantification were assigned a value of zero. This rule makes the recorded summary reflect the prespecified handling of measurements too low to quantify, but it also means a recorded zero under this rule should not automatically be read as proof that no drug was present. The actual medians and full ranges are not reported in the registry record, so the magnitude and pattern of plasma concentrations cannot be described from the registry information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It defines a median and full range for the primary concentration endpoint and describes the time points and handling of concentrations below the limit of quantification. It does not report the analysis procedures used to produce endpoint results, and no outcome analyses are listed. The explanations below distinguish the general meaning of the stated summaries from procedures that are not reported for this study.

What does the median describe?

In general, the median is the midpoint of an ordered set of measurements: half of the observations lie at or below it and half lie at or above it, allowing for ties. It is often used to describe a distribution when values are asymmetric or when unusually high or low measurements could make the arithmetic mean less representative of a typical observation. That is a general description of the statistic, not an account of the distribution in this study. The registry specifies that concentrations are summarized by median, but it does not report the median values.

What does the full range add?

In general, a full range gives the smallest and largest observed values in the summarized set. It conveys the span between extremes but does not show how observations are distributed between them. A range can be sensitive to extreme measurements, and it does not quantify uncertainty in the median. The registry lists full range as the dispersion measure for the primary endpoint, but the observed ranges are not reported in the registry record. No additional measure of spread or precision is specified there.

How should the concentration time points be understood?

Measurements are scheduled at baseline and at 2, 4, 8, 24, 48, 72, and 96 hours after the second dose. These are repeated time-specific observations in a pharmacokinetic study. In general, plotting or summarizing concentration against time can describe the timing and pattern of measured drug levels. However, the registry record does not say how repeated observations were modeled, whether participant-level correlations were accounted for, or whether the data were analyzed with a formal longitudinal method. Those details are not reported in the registry record.

The schedules differ across arms: one includes 2 and 48 hours, another 4 and 72 hours, another 24 and 96 hours, and one has a single collection at 8 hours. This arrangement means time points are not all collected under a single shared schedule across all arms. The non-randomized allocation and the registry’s warning about unlike-for-like arm comparisons are important when interpreting any descriptive differences. No adjusted analysis is reported.

What does assigning zero below the limit mean?

The primary endpoint description states that concentrations below the limit of quantification (LOQ) are assigned a value of zero. In general, the LOQ is the lower boundary at which a measurement can be quantified according to the assay procedure. Replacing below-limit measurements with zero is a data-handling convention; it does not show that the true concentration was exactly zero. The registry does not report the assay’s LOQ value, the frequency of below-limit measurements, or sensitivity analyses using another handling method.

Are the arm summaries independent?

The registry says results are reported per intervention based on each arm’s sampling times and notes that two participants were in multiple study arms. This overlap means arm summaries need not represent independent sets of participants. In general, analyses that compare groups or combine repeated measurements may need to account for dependence when observations are related. The registry record does not report whether or how such dependence was handled. It also does not report participant-level data, so this cannot be evaluated from the registered summaries.

What can significance tests or intervals tell a reader?

In general, a confidence interval describes a range of estimates compatible with a statistical procedure and conveys uncertainty about an estimated quantity. A hypothesis test evaluates data against a stated null model under specified assumptions. Neither is reported for the primary endpoint in the registry record. Without a stated comparison, estimate, interval, or test result, there is no basis for interpreting statistical significance or precision between collection schedules.

The record’s sample-size assumptions describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. Such planning illustrations are not observed power and do not establish that this study was designed around those assumptions. The actual planning rationale and the statistical analysis plan are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary plasma tenofovir concentration endpoint and secondary peripheral blood mononuclear cell concentration outcomes for tenofovir-diphosphate and emtricitabine-triphosphate. It lists no analyses. The record does not report whether a multiplicity adjustment was planned for multiple outcomes, time points, or arm comparisons, or whether any outcomes were designated as exploratory beyond their primary or secondary labels.

Multiplicity is a general statistical concern when several hypotheses are examined: the more comparisons considered, the greater the opportunity for apparently notable results to occur by chance if each is assessed separately. Methods such as adjusting significance thresholds or controlling a family-wise error rate may be used in some settings, but the registry record does not state that any such procedure was used. No inferential results are available to evaluate in this regard.

Missing-data procedures are not reported in the registry record. The endpoint description addresses measurements below the LOQ by assigning them a value of zero, but that is distinct from describing what happens when a specimen is not collected, a measurement is unavailable, or a participant does not contribute data at a scheduled time. The record does not state how such missing observations were handled or whether missingness was assessed.

The endpoint population is described as data reported per intervention based on the sample-collection time points for each arm. Drug concentration analysis was not performed in the pre-drug arm because no drug was administered. The record does not report additional analysis-population definitions, exclusions, or participant flow by endpoint. It notes that two participants were in multiple arms, so the arm-based reporting should not be interpreted as a set of disjoint populations.

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 registry reports no serious adverse events and no other adverse events in the listed groups. For the pre-drug group, the record lists 4 participants at risk for serious events and 4 at risk for other events, with 0 affected in each category. For Genvoya collection at 2 and 48 hours, it lists 14 at risk in each category and 0 affected. For collection at 4 and 72 hours, it lists 8 at risk in each category and 0 affected. For collection at 24 and 96 hours, it lists 11 at risk in each category and 0 affected. For the single time point collection, it lists 6 at risk in each category and 0 affected. The record lists 0 deaths in every group and no top serious-event terms.

These figures describe events recorded during the registry’s stated reporting period; they do not establish that an event could not occur. A zero count in a group is a report of no events recorded in that group, not proof of zero underlying risk. The registry record does not provide event-level details or a fuller account of safety surveillance. Because two participants were in multiple study arms, arm-level risk counts should not be added to infer a number of distinct participants.

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

The record establishes that this was a completed Phase 1 pharmacokinetic study with a stated aim of examining Genvoya uptake across body sites and time frames. It identifies median plasma tenofovir concentration as the primary endpoint, specifies baseline and post-dose sampling times, and describes assigning zero to concentrations below the LOQ. It also describes several distinct specimen-collection schedules and a pre-drug arm.

What it does not establish from the registered information is the actual concentration pattern. The endpoint medians and full ranges are not reported in the registry record, and no analyses are listed. A reader therefore cannot use the registered results to say how concentrations changed over time, whether schedules differed, or how precise any such difference might be. No effect estimate or confidence interval for a comparison is reported.

The design also does not support treating the arms as a randomized comparison. Allocation was non-randomized, masking was absent, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The pre-drug arm received no medication, and its drug concentration analysis was not performed. The different collection schedules provide descriptive time-specific sampling, but they do not by themselves establish a causal effect of one schedule versus another.

The study’s stated future-oriented context concerns possible on-demand peri-exposure HIV prophylaxis regimens. The registered endpoint is a drug concentration measure, not a clinical HIV outcome. The record does not report evidence about prevention outcomes or a clinical benefit. As a general statistical principle, pharmacokinetic measurements and clinical outcomes answer different questions; one should not be treated as a direct substitute for the other.

The appropriate reading is therefore narrow: the registry documents the study design, sampling schedule, endpoint definition, and adverse-event counts, but it does not provide the concentration results needed to assess the primary question quantitatively. It also does not report a statistical analysis plan, multiplicity procedures, or missing-data methods.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a carefully specified measurement question and an available numerical result. The registry defines a concentration endpoint, unit, summary measure, dispersion measure, time points, and below-LOQ rule. Those details clarify what investigators intended to describe, even though the concentration summaries themselves are not reported in the registry record.

The study also illustrates why design features matter before comparing group summaries. The arms were non-randomized and followed different specimen-collection schedules. In addition, the record notes that two participants were in multiple arms. These features affect how arm-level data would need to be interpreted and caution against treating arm summaries as independent or directly comparable without supporting analysis details. The registry itself says the arms are not a like-for-like control comparison.

The endpoint’s use of medians and full ranges highlights a useful general distinction. A measure of central tendency describes a typical location in the observed distribution, while a measure of spread describes variability. Neither alone supplies uncertainty for a between-group contrast. A reader would need reported estimates and suitable precision measures to judge how much the data support a comparison; those are not reported.

Finally, the concentration endpoint and the study’s intended future context should remain separate in interpretation. Pharmacokinetic measurements characterize measured drug levels at specified times. They are not, by themselves, reported clinical outcomes. The registry record offers a design description relevant to pharmacokinetic research, but the absence of registered concentration results means it cannot support a numerical conclusion about the observed levels or their differences.

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 important limitation for interpreting the registry record is that it does not report the primary endpoint values. Medians and full ranges for plasma tenofovir are not available, and the record lists no analyses. This prevents a numerical assessment of the concentration pattern or its precision.

The non-randomized, unmasked, sequential design limits causal interpretation and comparability across arms. The arms use different collection schedules, and the registry explicitly warns that they are not a like-for-like control comparison. The pre-drug arm is not a drug-exposed concentration comparator, because no drug was administered and concentration analysis was not performed for that group.

Arm membership overlaps: the record says two participants were in multiple study arms. Consequently, per-arm summaries may not be independent, and arm counts cannot be used as if they represented mutually exclusive groups. The record does not report an analysis method addressing that overlap.

The endpoint assigns zero to below-LOQ measurements, but the assay limit, frequency of such measurements, and any alternative handling analysis are not reported in the registry record. Missing-data procedures and additional analysis-population definitions are also not reported. The statistical analysis plan, multiplicity handling, sample-size justification, and any interim analyses are not reported in the registry record.

The registry lists no adverse events in the reported group counts, but it does not provide event-level details in the available record. These limitations concern what can be concluded from the registry information; they do not determine what may have been measured or analyzed outside the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens — NCT03976752.
• Registry record last updated 2021-08-13; status last verified 2021-07.
• Results first posted 2021-08-13.
• 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

The registry describes a completed Phase 1, non-randomized, unmasked, sequential study of Genvoya pharmacokinetics, with enrollment of 41. It lists a pre-drug arm and medication arms with specimen collection at 2 and 48 hours, 4 and 72 hours, 24 and 96 hours, or a single time point at 8 hours.

The primary endpoint is median plasma tenofovir concentration in ng/mL at baseline and specified times through 96 hours after the second dose, with full range as the dispersion measure. Below-LOQ concentrations were assigned zero. The registry record does not report primary concentration results and lists no analyses. It notes that two participants were in multiple arms. No serious or other adverse events and no deaths are recorded in the listed group counts.