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 Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics (NCT01386970), a non-randomized phase 4 study. The primary outcome is ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01386970 |
| Phase | Phase 4 |
| Condition | HIV |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 43 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Colorado, Denver |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled 43 participants and included HIV-negative and HIV-infected groups. The registry record also describes comparisons between men and women, but it does not report the group counts by sex or the characteristics of the participants.
Intervention
The intervention is listed as zidovudine 300mg and lamivudine 150mg as Combivir. The HIV-infected group was started on zidovudine-lamivudine based therapy. The HIV-negative group was used for comparison of intracellular drug concentrations.
Comparator
The primary comparison named in the registry record is HIV-negative versus HIV-infected participants for intracellular zidovudine-triphosphate concentration. The study description also names comparisons by sex and HIV status. Because allocation was non-randomized, these are observational group comparisons, not randomized treatment comparisons.
Primary question
At Day 12 of dosing, how did median intracellular zidovudine-triphosphate concentration, measured in pmol/10^6 cells, compare between HIV-negative and HIV-infected participants? The registry record gives the endpoint definition but not the medians, inter-quartile ranges, or a statistical test result. It therefore does not establish the direction or precision of the comparison.
The broader study description says that blood and blood-cell concentrations of zidovudine and lamivudine were evaluated in men versus women and in people with versus without HIV infection. It also describes correlating markers of side effects with blood levels. The stated hypothesis was that women and participants with HIV would have higher drug levels and higher markers of side effects. That is a hypothesis, not a finding: results for those comparisons are not reported in the registry record.
3. Trial Design
The study is identified as NCT01386970, with the title “Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics” and the official title “Sex and Disease Dependent Nucleoside Analog Toxicity.” It is listed as a Phase 4, parallel, non-randomized study with no masking. The registry record lists University of Colorado, Denver as the sponsor, an enrollment of 43, a start date of 2005-05, primary completion in 2008-07, and a completed status.
The design organizes participants into HIV-negative and HIV-infected groups. The HIV-negative group was used to compare intracellular zidovudine- and lamivudine-triphosphate concentrations with the HIV-infected group and to compare men with women. The HIV-infected group was started on zidovudine-lamivudine based therapy; intracellular concentrations were compared by sex and against the HIV-negative group. The intervention listing names zidovudine 300mg and lamivudine 150mg as Combivir.
Non-randomized allocation means assignment to the groups was not described as random. Therefore, differences between groups cannot automatically be attributed to HIV status or drug exposure alone. General statistical interpretation: when group membership is not randomized, measured and unmeasured differences between groups may contribute to an observed contrast. The registry record does not report adjustment methods or a protocol for addressing such differences.
The record lists 2 outcome measures and 0 analyses. It gives details for the named primary endpoint, but does not report outcome values or analysis results. The study’s stated interest in sex-related differences, drug concentrations, and markers of side effects should not be mistaken for documented findings on each of those questions.
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-negative | HIV-infected |
|---|---|---|
| STARTED | 20 | 23 |
| COMPLETED | 16 | 21 |
| NOT COMPLETED | 4 | 2 |
Reasons for not completing this period:
| Reason | HIV-negative | HIV-infected |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| Adverse Event | 4 | 1 |
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-negative | HIV-infected | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 23 | 43 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 20 | 23 | 43 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 8 | 6 | 14 |
| Sex: Female, Male: Male | Participants | 12 | 17 | 29 |
| Race/Ethnicity, Customized: African American | Participants | 4 | 7 | 11 |
| Race/Ethnicity, Customized: Non- African-American | Participants | 16 | 16 | 32 |
6. Primary Endpoint
The registry lists the primary outcome as ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject, measured over Day 12 of dosing.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | pmol/10^6 cells |
| Endpoint classification | not reduced to a single comparison |
The named primary endpoint is “ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject.” ZDV-TP refers in the record’s description to zidovudine triphosphate, an intracellular form of the drug. The endpoint is expressed in pmol/10^6 cells and is measured at Day 12 of dosing. The planned summary measure is the median, with the inter-quartile range as its dispersion measure.
Concentrations inside blood cells address a different measurement from concentrations in the blood itself. In general, measuring an intracellular drug form can be useful when the scientific question concerns exposure within cells rather than only drug circulating in blood. The inter-quartile range describes the spread of the middle half of observed values; it does not, by itself, give the uncertainty around a group comparison.
The registry record does not report the median concentration, inter-quartile range, number of participants contributing endpoint data, or a comparison estimate. It also does not report a confidence interval or p value for this endpoint. Consequently, the registry entry identifies what was to be measured and when, but it does not show the magnitude, direction, or precision of the primary comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record identifies a primary endpoint without reporting its numerical result. The endpoint is median intracellular zidovudine-triphosphate concentration at Day 12 of dosing, comparing HIV-negative with HIV-infected participants. No group medians, inter-quartile ranges, difference estimate, confidence interval, or p value are reported. The observed direction and size of the contrast therefore cannot be determined from the registry record.
The overall enrollment is 43, but the record does not state how many participants contributed measurements to the primary endpoint or how many were included in each sex or HIV-status subgroup analysis. Enrollment is not interchangeable with the number analyzed for an endpoint. Without those analysis counts, the precision of a comparison cannot be assessed from sample size alone.
The record describes the study as non-randomized. That matters because participants in the HIV-negative and HIV-infected groups may differ in ways other than HIV status or the study drug exposure. General statistical interpretation: randomization can balance measured and unmeasured characteristics on average, while a non-randomized comparison may be influenced by group differences. The registry record does not report adjusted estimates or methods for controlling confounding, so the extent to which such differences were addressed is unknown.
The study description also names sex comparisons and correlations between drug levels and markers of side effects. It states a hypothesis that women and people with HIV would have higher levels and markers. These aims and hypotheses do not supply results. The registry record does not report numerical findings for sex comparisons, lamivudine concentrations, side-effect markers, or correlations between markers and drug concentrations.
The record lists 0 analyses, and it reports 2 outcome measures. No inferential analysis is documented in the registry entry. In general, an estimate paired with a confidence interval helps readers distinguish the direction and plausible precision of a result; a p value addresses compatibility with a specified null model under the analysis assumptions. Neither is reported for the primary comparison. The absence of such results in the registry record is not evidence that the groups had equal concentrations, nor is it evidence of a difference.
The adverse-event counts are descriptive: serious adverse events and deaths are recorded as zero in both groups, while other adverse events are recorded for participants in each group. These counts do not establish a comparative safety effect. The registry record does not provide event details or a statistical comparison, and the non-randomized design limits direct causal interpretation.
9. Statistical Methods Explained
The registry describes the primary endpoint using the median and inter-quartile range. General statistical explanation: the median is the middle value after measurements are ordered. It is often useful for data that are skewed or contain unusually high or low observations because it is less influenced by extremes than the arithmetic mean. The inter-quartile range describes the middle half of the distribution, from the lower quartile to the upper quartile. It conveys variability among observed measurements, rather than uncertainty about the estimated median or the difference between groups.
That distinction is important. A group’s inter-quartile range describes how spread out individual concentrations are. A confidence interval for a group contrast instead describes uncertainty in an estimated comparison, under the statistical method used. The registry record specifies an inter-quartile range as the dispersion measure but does not report either group’s values or a confidence interval for the contrast. It also does not name a statistical test or model. A particular test should not be inferred just from the use of medians.
The measurement is intracellular zidovudine triphosphate, reported in pmol/10^6 cells, at Day 12 of dosing. General statistical explanation: specifying a measurement unit and time point helps define what a result represents. It does not, on its own, establish that all participants had measurements at that time, explain how missing measurements were handled, or indicate whether repeated measurements were collected. Those details are not reported in the registry record.
The comparison is between HIV-negative and HIV-infected groups in a non-randomized parallel study. General statistical explanation: in a randomized comparison, random assignment is intended to make groups comparable on average at the time of assignment. In non-randomized comparisons, group membership can be associated with other characteristics that also relate to the outcome. This can make a crude difference difficult to interpret as the effect of one factor. Adjustment for measured characteristics can sometimes address part of this problem, but no adjustment approach is reported in the registry record. Adjustment also cannot automatically remove bias from characteristics that were not measured or modeled.
The study description includes comparisons by sex and HIV status, as well as correlations between drug levels and side-effect markers. General statistical explanation: a correlation describes how two measured quantities vary together; it does not establish that one causes the other. Correlation estimates may also be sensitive to the distributions of the measurements and to influential observations. The registry record does not provide correlation coefficients, uncertainty intervals, or details about how these analyses were conducted.
Multiplicity refers generally to the increased chance of obtaining at least one apparently unusual result when many outcomes, groups, time points, or analyses are examined. A prespecified primary endpoint can help distinguish the main question from additional exploratory questions, but the registry entry does not report a multiplicity procedure or a detailed statistical analysis plan. It identifies 2 outcome measures and 0 analyses. The latter means no analysis results are listed in the record; it should not be read as proof that no analyses were conducted outside the registry entry.
Sample-size planning depends on assumptions about the effect to detect, variability, significance level, allocation, and statistical method. The record’s planning description characterizes sample-size illustrations as based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. It also specifies participants per arm for non-time-to-event illustrations. However, no numerical planning results are stated in the record. Such illustrations are planning calculations, not observed power and not evidence that the study was adequately powered for its endpoint. The registry record does not report the original sample-size justification.
General statistical explanation: over-dispersion occurs when data vary more than a chosen model assumes. If present and not handled, standard errors and resulting uncertainty statements from that model may be unreliable. The registry record does not identify a model or describe over-dispersion, so this is a general consideration rather than a claim about this study’s analysis.
For an interpretable analysis, readers would ordinarily need the number analyzed in each group, the group summaries, a defined comparison estimate, and an uncertainty measure. For this record, the endpoint definition is available, but those numerical results and analysis details are not reported in the registry record. No conclusion about statistical significance or the precision of the primary comparison can be drawn from the endpoint description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies 2 outcome measures and lists 0 analyses. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a complete statistical analysis plan. The number of analyses listed should be interpreted as the number documented in the registry record, not as confirmation that no analyses were performed elsewhere.
The study description refers to several scientific questions: differences by HIV status, differences by sex, drug concentrations for zidovudine and lamivudine, and correlations between drug levels and markers of side effects. Examining multiple outcomes or subgroup comparisons can raise multiplicity concerns. General statistical explanation: when many hypotheses are tested, the chance of at least one apparently noteworthy finding can increase unless the analyses are planned and interpreted with that context in mind. The record does not indicate how these questions were prioritized or addressed statistically.
Missing-data methods are not reported in the registry record. It does not give the number of participants with endpoint measurements, explain whether any measurements were missing, describe exclusions, or state how missing observations were handled. The analysis populations are also not defined. Therefore, the enrollment of 43 cannot be treated as the denominator for every endpoint or comparison.
These omissions limit assessment of selection, completeness, and robustness. They do not establish that data were missing or that a particular analysis population was used; those details are simply 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-negative | 0 | 20 | 0.0% |
| HIV-infected | 0 | 23 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| HIV-negative | 0 of 20 |
| HIV-infected | 0 of 23 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| HIV-negative | 7 of 20 |
| HIV-infected | 8 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HIV-negative | HIV-infected |
|---|---|---|---|
| Abnormal lab- Bilirubin | Hepatobiliary disorders | 7 of 20 | 8 of 23 |
| Abnormal Lab- Alanine Aminotransferase (ALT) | Hepatobiliary disorders | 0 of 20 | 7 of 23 |
| Abnormal Lab- Aspartate transaminase (AST) | Hepatobiliary disorders | 0 of 20 | 7 of 23 |
| Abnormal Lab- Amylase | Endocrine disorders | 0 of 20 | 7 of 23 |
| Abnormal Lab- albumin | Hepatobiliary disorders | 0 of 20 | 6 of 23 |
| Nausea, Vomiting, and/or Diarrhea | Gastrointestinal disorders | 4 of 20 | 1 of 23 |
For serious adverse events, the registry record lists 20 participants at risk and 0 affected in the HIV-negative group, and 23 at risk and 0 affected in the HIV-infected group. Deaths are recorded as 0 in each group. These are the serious-event counts reported in the registry record; the entry does not provide serious-event terms.
For other adverse events, the record lists 7 affected among 20 at risk in the HIV-negative group and 8 affected among 23 at risk in the HIV-infected group. These figures are counts of participants, not counts of individual event episodes, according to the way the registry fields are described. The record does not provide event descriptions or timing for these other events.
General statistical explanation: zero observed serious events does not prove that the underlying risk is zero. Interpretation depends on the amount of observation and the completeness of event reporting, among other considerations. The registry record does not report a formal comparison, confidence interval, or detailed safety-analysis method. Because the groups were not randomized, their event counts should not be treated as a causal comparison of treatment safety.
12. What the Result Does, and Does Not, Mean
The registry record documents a study of zidovudine and lamivudine pharmacokinetics, with attention to HIV status and sex. It defines a primary endpoint: median intracellular zidovudine-triphosphate concentration, measured in pmol/10^6 cells at Day 12 of dosing, comparing HIV-negative and HIV-infected participants. It also documents the study’s stated hypothesis and its broad interest in drug concentrations and side-effect markers.
What the record does not establish is the result of that primary comparison. It gives no medians, inter-quartile ranges, comparison estimate, confidence interval, or p value. It therefore cannot show whether one group had higher concentrations, how large any observed difference was, or how precisely it was estimated. The same caution applies to the stated sex comparisons, lamivudine findings, and correlations with side-effect markers: their results are not reported in the registry record.
The study’s non-randomized design also constrains interpretation. General statistical explanation: an observed difference between non-randomized groups may reflect the characteristic being compared, other differences between the groups, or a combination. Without reported adjustment details, the registry record does not allow readers to judge whether or how measured confounders were addressed. It cannot support a causal conclusion based on group differences alone.
The safety record reports zero serious adverse events and zero deaths in both groups, alongside other adverse-event counts. These descriptive entries do not show that serious events are impossible or that the groups have equivalent safety profiles. The registry record does not give event details or an inferential comparison.
In short, the entry is useful for identifying the clinical question, endpoint, design, and recorded adverse-event counts. It does not provide the outcome data needed to quantify or evaluate the primary pharmacokinetic result. Absence of reported results should not be interpreted as a null finding.
13. Why This Trial Matters Statistically
This study raises a clear statistical issue: pharmacokinetic questions can involve several related measurements and comparisons, while the registry record reports only limited endpoint and analysis detail. The primary endpoint is specifically defined by analyte, biological compartment, unit, comparison groups, and measurement time. Those specifications are essential for knowing what a result would mean, but they do not substitute for the result itself.
The non-randomized structure is also important. HIV status and sex are group characteristics, not randomized assignments in the design described. General statistical explanation: measured concentrations can vary with multiple characteristics, so a group contrast needs careful interpretation and, where appropriate, transparent adjustment. A reported estimate with its uncertainty and analysis methods would allow readers to assess what was compared and how stable the estimate might be. Those results are not reported in the registry record.
The study description also connects drug levels with markers of side effects. Statistically, that is a distinct question from comparing average or median concentrations between groups. A correlation can describe co-variation, but does not by itself establish a causal pathway. Clear reporting of the chosen measures, analysis population, and uncertainty would be needed to assess such findings.
Finally, the distinction between registered aims and reported evidence matters. The registry record states a hypothesis about higher levels in women and participants with HIV, but supplies no numerical results for that hypothesis. Separating a research question from its observed findings prevents an expectation from being mistaken for evidence and makes clear what additional outcome reporting is needed for a quantitative 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.
Several trial-specific details needed to interpret the endpoint are not reported in the registry record. Although enrollment is listed as 43, the record does not state the number with Day 12 measurements or the number contributing to the HIV-status comparison. It also does not report the actual median concentrations or inter-quartile ranges. The primary result’s direction and magnitude therefore cannot be assessed.
The record does not report results for the sex-based comparisons, lamivudine concentrations, or the described correlations between drug levels and side-effect markers. It gives no statistical test, model, adjustment variables, uncertainty intervals, or p values. The number and definitions of analysis populations, the handling of missing observations, and any exclusions are not reported in the registry record.
Because allocation was non-randomized, differences between HIV-negative and HIV-infected participants may reflect factors beyond the comparison of interest. The record does not describe whether such factors were measured or addressed. It also does not give the group counts by sex, limiting assessment of the precision or balance of the sex comparisons.
The adverse-event information is limited to counts of participants at risk and affected, plus deaths. Serious-event terms are not listed, and the record does not describe event timing, severity details, or a statistical safety comparison. These omissions restrict interpretation of both efficacy-related and safety-related findings; they do not establish that unreported analyses or data were absent.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics — NCT01386970.
- Registry record last updated 2020-03-16; status last verified 2020-03.
- Results first posted 2020-03-16.
- 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
NCT01386970 is listed as a completed Phase 4, parallel, non-randomized study with no masking and enrollment of 43. The registry record lists University of Colorado, Denver as sponsor, with study start in 2005-05 and primary completion in 2008-07.
The study examined zidovudine and lamivudine concentrations in relation to HIV status and sex. Its named primary endpoint compares median intracellular zidovudine-triphosphate concentrations between HIV-negative and HIV-infected participants at Day 12 of dosing, in pmol/10^6 cells, with inter-quartile range as the dispersion measure.
The record reports no numerical primary endpoint results and lists 0 analyses. Serious adverse events and deaths are recorded as zero in both groups; other adverse events are recorded for 7 of 20 HIV-negative participants and 8 of 23 HIV-infected participants. The registry record does not provide outcome estimates, inferential results, or detailed analysis methods.