Concentrations of Maraviroc in the Semen of HIV-Infected Men: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Concentrations of Maraviroc in the Semen of HIV-Infected Men (NCT01009034), a registered phase not stated study. The primary outcome is Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral..

2. Clinical Question

3. Trial Design

The registry record describes a completed study with enrollment of 14. Its arm description refers to 12 male HIV-positive patients who had been receiving stable antiretroviral therapy that included maraviroc for a minimum of three months. The difference between the enrollment figure and the number in the arm description is not explained in the registry record; it should not be interpreted as evidence of a particular number of withdrawals or exclusions.

The recorded intervention is measuring semen samples. Sampling was staggered: participants produced semen samples at different times relative to the morning dose, with samples scheduled 30 minutes to 1 hour before the dose on day 1 and at hours 1, 2, 4, 8, and 12 after drug ingestion on days 2-6. Blood samples were collected within 1 hour of the corresponding semen sample. This approach spreads sampling across the dose interval rather than describing repeated samples from every participant at every time point.

The registry does not describe randomized allocation or a control arm. The study therefore is not a randomized treatment comparison, and its record does not support a causal contrast between treatment groups. The start is listed as 2009-10, primary completion as 2011-12, and status as completed.

The stated secondary objectives concern the extent of maraviroc penetration into semen, semen-to-plasma ratios across the dosing interval, and the area under the concentration-time curve of maraviroc in semen. The record lists three outcome measures, but numerical outcome results are not reported in the registry record. A detailed protocol, recruitment flow, and analysis population are also 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:

Analysis population for the primary outcome, as defined in the registry: We used a staggered sampling approach in which semen samples were produced by participants over several days at different sampling times relative to the morning dose of antiretrovirals.

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.

Population: 10 HIV+ men on maraviroc with VL \<50 copies per M

6. Primary Endpoint

The registry lists the primary outcome as Semen to Plasma Ratio of HIV Concentration During the Dosing Interval for Dar, Evr, Mar & Ral., measured over Semen samples were collected 30 minutes to 1 hour before the morning dose of medication (day 1), and then at hours 1, 2, 4, 8, and 12 postdrug ingestion on days 2-6. Blood samples were collected within 1 hour of the semen sample..

The listed primary endpoint is titled as a semen-to-plasma ratio of HIV concentration during the dosing interval. Its unit is described as an inhibitory concentration ratio, and the record says that one value per participant was calculated by dividing the minimum HIV concentration in semen by the minimum HIV concentration in blood across the dosing interval. Semen and blood sampling were paired closely in time, with blood collected within 1 hour of a semen sample.

A ratio is used to express a quantity in one compartment relative to the corresponding quantity in another. In general, this can make the relationship between compartments easier to interpret than either measurement alone. Here, however, the endpoint wording requires care: the study's broad objective describes maraviroc concentrations in semen relative to HIV inhibitory concentrations, while the listed primary outcome describes a ratio of HIV concentrations in semen and blood. Those are not interchangeable descriptions, and the record does not provide an explanation reconciling them.

The endpoint description also reduces each participant's sampling over the dosing interval to a single minimum-based ratio. It therefore does not, on its own, convey every concentration measured at each time point or the full time course. The registry record does not report the endpoint values, their dispersion, or an estimate of precision. Without those results, the direction and magnitude of the observed ratio cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes repeated biological sampling at selected times around medication dosing and says the primary outcome is summarized as a median with an inter-quartile range. No numerical results or analysis details beyond the endpoint description are reported in the registry record. The concepts below explain the stated methods generally; they do not fill in unreported analysis decisions.

What does a median describe?

In general, the median is the central observation after values are ordered. It is less affected by a very high or low observation than the arithmetic mean. That can be useful for concentration data, which may be asymmetric or contain unusually large values. The median does not describe all features of a distribution, and it does not indicate the precision of an estimate by itself. In this record, the median is named as the summary parameter, but its value is not reported in the registry record.

What does the inter-quartile range add?

In general, the inter-quartile range describes the spread from the lower to the upper quartile, covering the middle half of the observed values. It gives information about variability among observations while being less sensitive to extremes than the full range. A median together with an inter-quartile range can therefore describe both a typical value and the dispersion of the central observations. It is not a confidence interval: it describes variation in the observed data rather than uncertainty about an estimated population value. The registry record names this dispersion measure but does not report its limits.

How does the sampling schedule relate to the dose interval?

The record describes a staggered sampling approach. Semen was scheduled 30 minutes to 1 hour before the morning medication dose on day 1, then at hours 1, 2, 4, 8, and 12 after drug ingestion on days 2-6. A corresponding blood sample was collected within 1 hour of the semen sample. In general, measurements at different post-dose times can help characterize concentration patterns over a dosing interval. A staggered design collects observations at different times across participants and days; it should not be mistaken for complete serial measurements from each participant at every scheduled time. The record does not give participant-by-time sampling counts or actual observed concentrations.

What does a ratio mean?

In general, a ratio expresses one quantity in relation to another. The listed endpoint describes a participant-level ratio formed from the minimum HIV concentration in semen and the minimum HIV concentration in blood over the dosing interval. Using one ratio per participant creates a summary that is different from reporting every sample or separately analyzing each time point. The record does not describe further adjustments, transformations, or a model for these values. It also does not reconcile this HIV-concentration ratio with the broader objective of measuring maraviroc concentrations relative to inhibitory concentrations.

Why can variability matter?

In general, measurements from people can vary even when they follow the same regimen. Variability in a semen-to-plasma relationship may be relevant to describing how consistently a measured drug concentration appears in a compartment across individuals or sampling times. A measure of central tendency alone would not capture that heterogeneity; a dispersion measure gives complementary information. The registry lists variability in penetration as an objective, but does not report a numerical variability estimate. The record also does not say whether variability was assessed between people, within people over time, or both.

What can statistical precision show?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the method. Its width reflects uncertainty and depends on factors such as sample size and variability. A narrow interval indicates greater precision than a wide interval, but neither is itself a probability that a particular value is true. No confidence interval is reported in the registry record. There is also no reported test statistic or p-value for the primary outcome, so statistical evidence against a specified null value cannot be evaluated.

What is not specified about the analysis?

The registry record does not report a statistical analysis plan, the method used to handle missing samples, whether any values were excluded, or the population included in each outcome analysis. It lists three outcome measures and no analyses. It also does not report an interim analysis or a sample-size justification. These omissions mean the planned summary can be identified, but the implementation and completeness of the analysis cannot be assessed. General methodological expectations should not be substituted for decisions that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including a primary endpoint and secondary objectives concerning maraviroc penetration into semen and the area under the concentration-time curve in semen. Considering several outcomes can raise a multiplicity issue: in general, the more hypotheses or comparisons assessed, the greater the opportunity for a chance finding if each is tested separately. A prespecified hierarchy, adjustment, or descriptive approach can address different multiplicity concerns, but the registry record does not report a statistical plan or a multiplicity procedure. It also does not report numerical outcome tests, so the impact of any procedure cannot be assessed.

The record describes sampling at multiple times and across different participants in a staggered manner. It does not report how many samples were collected at each time, whether all scheduled samples were available, or how incomplete sampling was handled. Missing data can affect summaries when the availability of measurements is related to the values themselves or to participant characteristics. In general, complete-case summaries and methods that use partial records answer questions under different assumptions. No missing-data method or sensitivity analysis is reported in the registry record.

The registry enrollment is 14, whereas the arm description names 12 male HIV-positive patients. The record does not explain the difference or identify the analysis population for the primary and secondary outcomes. It is therefore not possible to infer the number included in each analysis, the reason for any difference, or whether all enrolled participants contributed outcome data. An intention-to-treat analysis is not applicable as a stated comparison in the absence of randomized treatment groups, and the registry record does not describe another analysis population. These reporting gaps limit assessment of completeness and potential selection effects.

11. Safety Results

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

Other (non-serious) adverse events

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

The adverse-event record lists 12 Male HIV-positive Patients as the group, with 10 at risk for serious adverse events and 0 affected. For other adverse events, it also lists 10 at risk and 0 affected. These are the posted counts for the recorded categories; they should be read with their listed at-risk denominators rather than as counts out of the enrollment figure of 14.

The death count is null, so a death count is not reported in the registry record. A zero affected count means that no events in that category are recorded among those listed as at risk; it does not establish that no event occurred among every enrolled participant or that all participants had complete safety follow-up. The record does not explain why the at-risk count is 10 or how safety follow-up was conducted.

These figures are descriptive and do not provide a comparison between treatments. The study does not have a reported randomized control group, and the registry record does not report an adverse-event analysis or statistical comparison. The counts therefore cannot establish comparative safety or rule out uncommon events.

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

The study's stated purpose was to assess maraviroc concentrations in semen during the dosing interval, examine drug penetration into semen, and describe related concentration measures. Its sampling description indicates that semen and blood were collected at multiple scheduled times, using staggered sampling across participants. These details show what the investigation set out to measure, not what the measurements demonstrated.

The record does not report numerical values for the primary endpoint or the secondary outcomes. It therefore does not show whether semen concentrations exceeded the 50% or 95% HIV inhibitory concentrations, what the semen-to-plasma ratio was, how much the ratio varied, or what the area under the concentration-time curve was. No conclusion about the magnitude or precision of these outcomes can be drawn from the registry record.

The distinction between the broad objective and the primary endpoint wording is also important. The objective concerns maraviroc concentration relative to HIV inhibitory concentrations; the listed primary outcome instead describes a ratio of minimum HIV concentrations in semen and blood. Without a reported explanation or results, that endpoint description cannot be treated as a direct numerical answer to the broader drug-concentration question.

The record is not a randomized comparison of treatment groups. It can inform readers about the intended sampling questions and recorded study design, but not about a causal difference between assigned treatments. The registry record also does not provide a statistical plan, analysis population, missing-data approach, or estimate of precision. These limitations define what can and cannot be interpreted from the entry; they do not substitute for outcome findings that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why the endpoint definition matters as much as the broad research objective. A question about drug concentrations relative to inhibitory concentrations is not identical to a ratio comparing HIV concentrations in semen and blood. When the stated objective and listed primary endpoint use different quantities, readers need a clear operational definition and results tied to that definition. The registry record does not explain the difference or report numerical outcomes.

The staggered sampling plan also highlights a design issue common to pharmacokinetic research: observations are collected in relation to dose timing, and the timing and pairing of specimens shape what can be summarized. The record specifies semen sampling before and after dosing and corresponding blood sampling within 1 hour. That schedule provides context for interpreting the intended measurements, while the absence of time-specific data prevents assessment of the observed concentration pattern.

Statistically, the study underscores the distinction between a summary measure and a complete account of the data. A median and inter-quartile range can describe a central value and dispersion, but do not supply a confidence interval or answer questions about missing observations. The registry names those summary measures without posting their values. Likewise, enrollment is not necessarily the same as the number contributing to each endpoint, and the record does not explain the difference between the enrollment and arm-description counts.

Finally, a completed status does not itself communicate results. Transparent reporting of outcome values, uncertainty, participant flow, and analysis decisions is needed to judge how precisely a study answers its question. This record is useful for identifying the population, sampling approach, and intended objectives, while its unreported outcome and analysis details constrain statistical interpretation.

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 of the registry entry is that numerical primary and secondary outcome results are not reported in the registry record. There is consequently no reported estimate of the primary ratio, no dispersion value, no confidence interval, and no reported test result. The central study questions about concentrations, inhibitory thresholds, penetration, and area under the concentration-time curve cannot be answered from the recorded results.

The primary endpoint title and description appear to concern HIV concentrations in semen and blood, whereas the broader objective concerns maraviroc concentrations in semen relative to HIV inhibitory concentrations. The registry record does not explain how these descriptions relate. This creates uncertainty about exactly which quantity the primary endpoint was intended to represent and how it should be connected to the study objective.

The enrollment figure is 14, while the arm description refers to 12 male patients. No participant flow or explanation is reported. The adverse-event counts use 10 at risk, but the record does not state how that denominator relates to enrollment or outcome analyses. The number of participants with complete samples, and the analysis population for each endpoint, are not reported in the registry record.

The staggered sampling schedule is described, but the record does not provide actual sample counts by time, details of missed samples, or methods for handling incomplete observations. It does not report a statistical analysis plan, sample-size justification, multiplicity approach, interim analyses, or sensitivity analyses. Since the study is not described as a randomized comparison, it also cannot provide a randomized treatment contrast. These reporting limitations restrict evaluation of both the data and the statistical methods used.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Concentrations of Maraviroc in the Semen of HIV-Infected Men — NCT01009034.
• Registry record last updated 2014-09-09; status last verified 2014-09.
• Results first posted 2014-09-09.
• 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 record describes a completed study of maraviroc concentrations and sampling in semen among men with HIV receiving stable antiretroviral therapy. Enrollment is listed as 14; the arm description refers to 12 male HIV-positive patients. The recorded intervention is measuring semen samples, and no randomized comparator is described.

Sampling was staggered around medication dosing, with paired blood samples collected within 1 hour of semen samples. The broad objectives concern semen concentrations relative to HIV inhibitory concentrations, drug penetration, and area under the concentration-time curve. The listed primary endpoint describes a semen-to-plasma ratio of HIV concentration, a wording distinction the record does not explain.

Three outcome measures are listed, but numerical outcome results and analyses are not reported in the registry record. The record also does not report an analysis population, missing-data method, or statistical analysis plan. Safety counts list 0 affected among 10 at risk for serious events and 0 affected among 10 at risk for other events; the death count is not reported in the registry record.