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 Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy (NCT00042289), a registered phase not stated study. The primary outcome is PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00042289 |
| Phase | Phase not stated |
| Condition | HIV Infections |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 1578 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
The study included pregnant women taking a range of antiretroviral or tuberculosis drugs, as well as their infants for some assessments. Some groups included HIV-infected women; the record also describes HIV-uninfected women receiving tuberculosis treatment. Postpartum assessments involved HIV-infected women starting hormonal contraceptives. The primary outcome population was mothers with intensive pharmacokinetic results who were taking the dose under study at the relevant period.
Intervention
The record describes a prospective Phase IV study of drug concentrations and pharmacokinetic parameters. It covers multiple antiretroviral regimens, tuberculosis drugs, and postpartum combinations involving oral contraceptives or an etonogestrel implant. The study also assessed drug levels in blood and/or vaginal secretions.
Comparator
There is no single control group or common comparator. The registry states that this was not a randomized comparison and that allocation was not stated. The listed arms represent different drug exposures and populations, so comparisons between them are not like-for-like controlled comparisons.
Primary question
The primary outcome describes the area under the plasma concentration curve from 0 to 12 hours, reported as a median and interquartile range for antiretroviral and tuberculosis drugs. Measurements were planned at pregnancy and postpartum periods, with timing depending on the study arm. The central question was how these pharmacokinetic measurements were characterized across the periods and drug exposures studied, not whether one treatment outperformed a randomized control.
3. Trial Design
This was a prospective Phase IV clinical study, identified as IMPAACT P1026s. The registry describes its purpose as evaluating pharmacokinetics of antiretroviral and tuberculosis medications in pregnant women and their infants. It also evaluated pharmacokinetics of certain antiretrovirals in postpartum women before and after starting hormonal contraceptives. Drug concentrations were assessed in blood and/or vaginal secretions.
The registry reports enrollment of 1578 and status COMPLETED. The study start date was 2003-06-09 and the primary completion date was 2020-09-30. The sponsor was the National Institute of Allergy and Infectious Diseases (NIAID). The listed arms encompass a wide range of drugs and dosing regimens, and include women with different HIV and tuberculosis treatment circumstances. Some assessments concern infants, while postpartum arms include hormonal contraceptive exposures.
The primary outcome was AUC12, expressed in mg*hour/L and summarized by median and interquartile range. Measurements were described for the 2nd trimester, the 3rd trimester, and postpartum; the exact postpartum interval differed by study arm. Participants could enter at different periods under the study design, so the registry does not expect every participant to contribute measurements at every period.
The registry identifies this as not a randomized comparison, and allocation is not stated. The listed treatment groups therefore should not be read as randomized treatment arms or as equivalent groups assigned to provide a direct control comparison. Further details about the protocol, site structure, and statistical analysis plan 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.
Only the first 6 of 47 groups are shown.
Overall Study
| Stage | DRV/RTV 600 or 800 or 900/100mg b.i.d. Then 800 or 900/100mg b.i.d. Then 600/100mg b.i.d. | DTG 50mg q.d. | TAF 25mg q.d. | TAF 10mg q.d. w/COBI | TAF 25mg q.d. w/COBI or RTV Boosting | EVG/COBI 150/150mg q.d. |
|---|---|---|---|---|---|---|
| STARTED | 26 | 30 | 27 | 33 | 29 | 31 |
| Infant Started | 25 | 30 | 27 | 32 | 28 | 31 |
| Infant Completed | 21 | 28 | 27 | 29 | 26 | 25 |
| COMPLETED | 19 | 29 | 27 | 25 | 26 | 25 |
| NOT COMPLETED | 7 | 1 | 0 | 8 | 3 | 6 |
Reasons for not completing this period:
| Reason | DRV/RTV 600 or 800 or 900/100mg b.i.d. Then 800 or 900/100mg b.i.d. Then 600/100mg b.i.d. | DTG 50mg q.d. | TAF 25mg q.d. | TAF 10mg q.d. w/COBI | TAF 25mg q.d. w/COBI or RTV Boosting | EVG/COBI 150/150mg q.d. |
|---|---|---|---|---|---|---|
| Lost to Follow-up | 3 | 0 | 0 | 1 | 3 | 3 |
| Other reason | 0 | 0 | 0 | 2 | 0 | 0 |
| Severe debilitation, unable to continue | 0 | 0 | 0 | 0 | 0 | 0 |
| Site closed | 0 | 0 | 0 | 0 | 0 | 0 |
| Participant not willing to adhere to requirements | 0 | 0 | 0 | 3 | 0 | 0 |
| Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrawal by Subject | 4 | 1 | 0 | 2 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: All mothers with intensive pharmacokinetic (PK) results taking the dose under study at that time period (2nd trimester, 3rd trimester or postpartum). Because participants could enter the study at different time period per the study design, they are not expected to have results at every time 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.
Population: The baseline analysis population is all mothers enrolled. Each study arm was designed as a separate single-arm evaluation. Participants were able to enroll in multiple arms, simultaneously; thus, the reporting groups are not mutually exclusive and totals do not represent the number of unique participants. There were 1037 unique mothers, including 8 who enrolled in 3 arms and 60 who enrolled in 2 arms.
Only the first 6 of 48 groups are shown.
| Characteristic | Unit | DRV/RTV 600 or 800 or 900/100mg b.i.d. Then 800 or 900/100mg b.i.d. Then 600/100mg b.i.d. | DTG 50mg q.d. | TAF 25mg q.d. | TAF 10mg q.d. w/COBI | TAF 25mg q.d. w/COBI or RTV Boosting | EVG/COBI 150/150mg q.d. |
|---|---|---|---|---|---|---|---|
| Participants analysed | 26 | 30 | 27 | 33 | 29 | 31 | |
| Age, Continuous | years | 28.8 (21.3 to 34.1) | 31.8 (26.7 to 33.8) | 29.3 (24.0 to 35.1) | 33.6 (26.6 to 35.2) | 30.8 (25.3 to 36.1) | 32.1 (26.3 to 34.6) |
| Sex: Female, Male: Female | Participants | 26 | 30 | 27 | 33 | 29 | 31 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White Non-Hispanic | Participants | 0 | 3 | 4 | 3 | 1 | 3 |
| Race/Ethnicity, Customized: Black Non-Hispanic | Participants | 13 | 21 | 8 | 20 | 14 | 22 |
| Race/Ethnicity, Customized: Hispanic (Regardless of Race) | Participants | 12 | 4 | 14 | 10 | 13 | 5 |
| Race/Ethnicity, Customized: Asian, Pacific Islander | Participants | 1 | 1 | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: American Indian, Alaskan Native | Participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: More Than One Race | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as PK Parameter: Area Under the Curve From 0 to 12 Hours (AUC12) With Median (IQR) for ARVs and TB Drugs, measured over Measured in 2nd trimester (20-26 wks gestation), 3rd trimester (30-38 wks gestation), and either 2-3 wks, 2-8 wks, or 6-12 wks postpartum depending on study arm. Blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hrs post dosing..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | mg*hour/L |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the area under the plasma concentration-time curve from 0 to 12 hours, or AUC12, reported as a median with an interquartile range for antiretroviral and tuberculosis drugs. It is expressed in mg*hour/L. The registry says pharmacokinetic parameters were determined from plasma concentration-time profiles using noncompartmental methods, with AUC12 calculated by the linear trapezoidal rule.
As a general statistical concept, an area under a concentration-time curve represents integrated drug exposure over the measured interval. It incorporates concentration information across the interval rather than describing only a single blood draw. The registry describes blood sampling before dosing and at 1, 2, 4, 6, 8, and 12 hours after dosing. The AUC12 endpoint therefore characterizes exposure over the specified 12-hour period, not exposure over an entire day or a clinical outcome.
Reporting a median and interquartile range describes the central value and spread of the observed pharmacokinetic measurements without requiring a normal-shaped distribution. The endpoint can help characterize whether measured exposure differs across pregnancy and postpartum periods, but the registry record does not report the numerical AUC12 estimates or their interquartile ranges. It also does not report a single overall comparison of these measurements across all drugs and arms.
A pharmacokinetic measurement is not by itself evidence of clinical benefit, harm, or comparative effectiveness. Interpreting exposure in relation to a clinical target would require information that is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a broad pharmacokinetic study rather than a single randomized treatment comparison. Its primary endpoint is a descriptive summary of drug exposure: median AUC12 and interquartile range for each drug and relevant study period. The record explains how the measurements were collected and calculated, but the numerical primary-outcome results are not reported in the registry record. Consequently, the stated information does not establish the direction or magnitude of exposure changes during pregnancy or postpartum.
The study covered multiple antiretroviral and tuberculosis drug regimens and included maternal, infant, and postpartum contraceptive assessments. These groups are defined by different drugs, dosing schedules, eligibility circumstances, and measurement periods. A contrast between two listed arms could reflect differences in more than the drug itself. Since the registry says the study was not randomized and allocation was not stated, the arms should not be interpreted as exchangeable groups created to estimate a causal treatment effect.
The primary outcome population consists of mothers with intensive pharmacokinetic results who were taking the dose under study at the relevant period. The record notes that participants could enter at different periods and were not expected to have data at every period. Thus, any period-specific summaries may describe different subsets of participants. The registry does not report the number with evaluable AUC12 results for each drug and period in the registry record for this analysis, nor does it report how missing measurements were handled.
The record lists 43 outcome measures and 126 analyses. This indicates that the study report covers many endpoints and analysis records, but it does not identify the multiplicity procedure or explain which analyses were designated confirmatory. The number of analyses alone cannot establish how evidence should be weighted or whether any reported finding would remain persuasive after accounting for multiple testing.
Safety information is organized by regimen and maternal or infant group. Those figures describe events recorded within each listed group; they are not a randomized safety comparison. The record includes some groups with small numbers at risk, and individual group counts should be read in that context. No single pooled safety estimate should be inferred by combining groups.
Overall, the registry supplies study purpose, outcome definitions, sampling procedures, and group-level safety counts, but not numerical AUC12 outcome estimates. The available record therefore supports understanding what was measured and how the design constrains interpretation, not conclusions about the size or clinical importance of pharmacokinetic differences.
9. Statistical Methods Explained
The primary outcome is a pharmacokinetic summary, not a binary clinical endpoint or a time-to-event outcome. The registry says the parameter was calculated from plasma concentration-time profiles using noncompartmental methods. AUC12 was determined with the linear trapezoidal rule. In general, this rule approximates the area between observed concentration measurements by joining adjacent points with straight segments and combining the segment areas. The method depends on the observed sampling schedule and does not, by itself, establish a clinical consequence of the measured exposure.
What does AUC12 represent?
As a general concept, AUC summarizes concentration over a time interval, capturing exposure across multiple measurements rather than at a single moment. Here the specified interval runs from 0 to 12 hours, and the unit is mg*hour/L. The registry describes samples taken before dosing and at 1, 2, 4, 6, 8, and 12 hours post dosing. AUC12 should not be treated as a measure of exposure outside that interval. The record does not state a clinical threshold or target against which the AUC12 values should be judged.
Why report a median and interquartile range?
The primary outcome is summarized by median and interquartile range. In general, the median gives the middle of an ordered set of measurements, while the interquartile range describes the spread of the middle portion of those measurements. This form of summary can be useful when values are skewed or when extreme observations make a mean and standard deviation less representative. It does not describe every individual value, and the interquartile range is not a confidence interval for the median. Numerical medians and interquartile ranges for the primary outcome are not reported in the registry record.
How should the study periods be understood?
The stated measurement periods are the 2nd trimester, the 3rd trimester, and postpartum. The postpartum window varies by study arm and is described as either 2-3 weeks, 2-8 weeks, or 6-12 weeks postpartum. These differing windows matter when interpreting summaries: a postpartum measurement at one interval is not automatically comparable to a measurement at another interval. The record also states that participants could enter at different periods, so not every participant was expected to have results at every period. The analysis population is mothers with intensive pharmacokinetic results taking the dose under study at that period.
As a general principle, summaries based on different participants or different assessment times can be influenced by the composition of the observed groups. A within-person comparison may control for stable individual characteristics when the same person contributes measurements at multiple periods, but the registry does not describe a specific paired analysis or state that every period comparison used the same participants. The analytic handling of incomplete or irregular measurements is not reported in the registry record.
What do the arms allow researchers to compare?
The study includes numerous drug regimens and groups, rather than one shared intervention and a single common control. The registry characterizes the trial as not randomized, with allocation not stated. In general, random assignment helps balance measured and unmeasured participant characteristics between treatment groups. Without randomized allocation, observed differences between arms can reflect differences in participants, regimen, site, eligibility, or assessment timing as well as drug exposure. The listed arms should therefore not be interpreted as a like-for-like control comparison.
Comparisons across pregnancy and postpartum may be scientifically informative as descriptions of pharmacokinetic patterns, but causal interpretation requires a defined comparison and appropriate analysis. The registry does not provide an analysis model, adjustment variables, or a complete statistical analysis plan. Whether estimates were adjusted for covariates, and how repeated measurements were incorporated, are not reported in the registry record.
How should planning illustrations be read?
Any sample-size illustrations use the stated planning assumptions: two-sided significance level 0.05, equal allocation between two arms, normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is used; other illustrations are expressed as participants per arm. These are planning illustrations, not the study’s own design justification and not observed power. Equal allocation is an assumption for illustration, not evidence that the actual study groups were balanced or randomized. No sample-size justification or power calculation from the study protocol is reported in the registry record.
No recalculated treatment-effect estimate is described in the registry record. Accordingly, there is no recalculated estimate to set against a sponsor analysis, and no basis to infer a result from sample-size planning alone. Planning calculations concern hypothetical future designs and do not show that a study had adequate precision for every drug, period, or outcome.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 43 outcome measures and 126 analyses. With many drugs, maternal and infant groups, pregnancy and postpartum periods, and pharmacokinetic outcomes, the study entails a broad set of reported measurements. As a general statistical issue, testing or examining many outcomes can increase the chance that some findings appear notable by chance, especially if analyses are selected after results are known. The record does not report a multiplicity adjustment, hierarchy of outcomes, or distinction between confirmatory and exploratory analyses. The number of analyses alone does not reveal how multiplicity was handled.
For the primary outcome, the stated analysis population is mothers with intensive pharmacokinetic results who were taking the dose under study at that time period. Participants could enter at different periods, and the registry does not expect each participant to have results at every period. Therefore, the sets contributing data may vary by period and regimen. The registry record does not report period-specific missingness, reasons for missing measurements, or the method used to address incomplete data.
The listed outcome descriptions also include cord-to-maternal blood concentration ratios and infant plasma washout measures. Their presence does not specify how missing samples or values below a measurement threshold were treated; those procedures are not reported in the registry record. A complete statistical analysis plan, interim analysis procedures, and sample-size justification are likewise not reported in the registry record.
These omissions limit assessment of how much the analysis plan anticipated the range of outcomes and how representative each analysis population was. They do not show that a particular method was absent from the study itself; they mean that the method is 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 |
|---|---|---|---|
| ABC 300mg b.i.d. MOTHER | 0 | 26 | 0.0% |
| ATV/COBI 300/150 mg q.d. INFANT | 3 | 12 | 25.0% |
| ATV/COBI 300/150 mg q.d. MOTHER | 3 | 12 | 25.0% |
| ATV/RTV 300/100mg q.d. INFANT | 0 | 22 | 0.0% |
| ATV/RTV 300/100mg q.d. MOTHER | 1 | 22 | 4.5% |
| ATV/RTV 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. INFANT | 6 | 38 | 15.8% |
| ATV/RTV 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. MOTHER | 0 | 38 | 0.0% |
| ATV/RTV/TFV 300/100/300mg q.d. With 30-35ug EE MOTHER | 2 | 28 | 7.1% |
| ATV/RTV/TFV 300/100/300mg q.d. With ENG MOTHER | 0 | 25 | 0.0% |
| At Least Two 2nd Line TB Drugs w/ or w/Out ARVs INFANT | 8 | 14 | 57.1% |
| At Least Two 2nd Line TB Drugs w/ or w/Out ARVs MOTHER | 4 | 13 | 30.8% |
| DDI 400mg or 250mg q.d. INFANT | 0 | 4 | 0.0% |
| DDI 400mg or 250mg q.d. MOTHER | 0 | 18 | 0.0% |
| DRV/COBI 800/150 mg q.d. INFANT | 7 | 27 | 25.9% |
| DRV/COBI 800/150 mg q.d. MOTHER | 5 | 28 | 17.9% |
| DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d With 30-35ug EE MOTHER | 0 | 2 | 0.0% |
| DRV/COBI 800/150mg q.d. or ATV/COBI 300/150mg q.d With ENG MOTHER | 0 | 6 | 0.0% |
| DRV/RTV 600 or 800 or 900/100mg b.i.d. Then 800 or 900/100mg b.i.d. Then 600/100mg b.i.d. INFANT | 0 | 25 | 0.0% |
| DRV/RTV 600 or 800 or 900/100mg b.i.d. Then 800 or 900/100mg b.i.d. Then 600/100mg b.i.d. MOTHER | 3 | 26 | 11.5% |
| DRV/RTV 600/100mg b.i.d. INFANT | 1 | 9 | 11.1% |
| DRV/RTV 600/100mg b.i.d. MOTHER | 0 | 36 | 0.0% |
| DRV/RTV 800/100mg q.d. MOTHER | 0 | 32 | 0.0% |
| DTG 50mg q.d. INFANT | 7 | 30 | 23.3% |
| DTG 50mg q.d. MOTHER | 3 | 30 | 10.0% |
| EFV 600 mg q.d. (Outside THA) INFANT | 8 | 26 | 30.8% |
| EFV 600 mg q.d. (Outside THA) MOTHER | 5 | 27 | 18.5% |
| EFV 600mg q.d. INFANT | 0 | 21 | 0.0% |
| EFV 600mg q.d. MOTHER | 0 | 25 | 0.0% |
| EFV 600mg q.d. and at Least One 1st Line TB Drug INFANT | 7 | 23 | 30.4% |
| EFV 600mg q.d. and at Least One 1st Line TB Drug MOTHER | 6 | 24 | 25.0% |
| EFV 600mg q.d. With 30-35ug EE MOTHER | 3 | 29 | 10.3% |
| EFV 600mg q.d. With ENG MOTHER | 0 | 28 | 0.0% |
| ETR 200mg b.i.d. INFANT | 1 | 6 | 16.7% |
| ETR 200mg b.i.d. MOTHER | 1 | 16 | 6.2% |
| EVG/COBI 150/150mg q.d. INFANT | 5 | 31 | 16.1% |
| EVG/COBI 150/150mg q.d. MOTHER | 5 | 31 | 16.1% |
| FPV/RTV 700/100 b.i.d. INFANT | 2 | 9 | 22.2% |
| FPV/RTV 700/100 b.i.d. MOTHER | 0 | 30 | 0.0% |
| FTC 200mg q.d. INFANT | 0 | 5 | 0.0% |
| FTC 200mg q.d. MOTHER | 1 | 21 | 4.8% |
| IDV/RTV 400/100mg q.d. (Only THA) INFANT | 0 | 26 | 0.0% |
| IDV/RTV 400/100mg q.d. (Only THA) MOTHER | 0 | 26 | 0.0% |
| IDV/RTV 800/100mg b.i.d. MOTHER | 0 | 1 | 0.0% |
| LPV/RTV 400/100 b.i.d. With 30-35ug EE MOTHER | 0 | 27 | 0.0% |
| LPV/RTV 400/100 b.i.d. With ENG MOTHER | 0 | 27 | 0.0% |
| LPV/RTV 400/100mg b.i.d. MOTHER | 0 | 17 | 0.0% |
| LPV/RTV 400/100mg b.i.d. Then 533/133mg b.i.d. MOTHER | 0 | 29 | 0.0% |
| LPV/RTV 400/100mg b.i.d. Then 600/150mg b.i.d. Then 400/100mg b.i.d. (Only African Sites) INFANT | 3 | 25 | 12.0% |
| LPV/RTV 400/100mg b.i.d. Then 600/150mg b.i.d. Then 400/100mg b.i.d. (Only African Sites) MOTHER | 3 | 25 | 12.0% |
| LPV/RTV 400/100mg b.i.d. Then 600/150mg b.i.d. Then 400/100mg b.i.d. MOTHER | 1 | 35 | 2.9% |
| LPV/RTV 800/200mg b.i.d. and at Least One 1st Line TB Drug INFANT | 2 | 2 | 100.0% |
| LPV/RTV 800/200mg b.i.d. and at Least One 1st Line TB Drug MOTHER | 0 | 2 | 0.0% |
| MVC 150 or 300mg b.i.d. INFANT | 0 | 4 | 0.0% |
| MVC 150 or 300mg b.i.d. MOTHER | 0 | 12 | 0.0% |
| NFV 1250mg b.i.d. MOTHER | 0 | 29 | 0.0% |
| NFV 1250mg b.i.d. Then 1875mg b.i.d. Then 1250mg b.i.d. MOTHER | 2 | 18 | 11.1% |
| NVP 200mg b.i.d. MOTHER | 0 | 12 | 0.0% |
| No ARVs and at Least Two 1st Line TB Drugs INFANT | 7 | 27 | 25.9% |
| No ARVs and at Least Two 1st Line TB Drugs MOTHER | 6 | 27 | 22.2% |
| RAL 400mg b.i.d. INFANT | 1 | 6 | 16.7% |
| RAL 400mg b.i.d. MOTHER | 0 | 43 | 0.0% |
| RPV 25mg q.d. INFANT | 3 | 30 | 10.0% |
| RPV 25mg q.d. MOTHER | 2 | 32 | 6.2% |
| TAF 10mg q.d. w/COBI INFANT | 10 | 32 | 31.2% |
| TAF 10mg q.d. w/COBI MOTHER | 7 | 33 | 21.2% |
| TAF 25mg q.d. INFANT | 4 | 27 | 14.8% |
| TAF 25mg q.d. MOTHER | 4 | 27 | 14.8% |
| TAF 25mg q.d. w/COBI or RTV Boosting INFANT | 5 | 28 | 17.9% |
| TAF 25mg q.d. w/COBI or RTV Boosting MOTHER | 5 | 29 | 17.2% |
| TFV 300mg q.d. MOTHER | 0 | 28 | 0.0% |
| TFV/ATV/RTV 300/300/100mg q.d. INFANT | 2 | 21 | 9.5% |
| TFV/ATV/RTV 300/300/100mg q.d. MOTHER | 1 | 25 | 4.0% |
| TFV/ATV/RTV 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. INFANT | 2 | 35 | 5.7% |
| TFV/ATV/RTV 300/300/100mg q.d. Then 300/400/100mg q.d Then 300/300/100mg q.d. MOTHER | 0 | 35 | 0.0% |
| TPV/RTV 500/200mg b.i.d. MOTHER | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ABC 300mg b.i.d. MOTHER | 0 of 26 |
| ATV/COBI 300/150 mg q.d. INFANT | 0 of 12 |
| ATV/COBI 300/150 mg q.d. MOTHER | 0 of 12 |
| ATV/RTV 300/100mg q.d. INFANT | 0 of 22 |
| ATV/RTV 300/100mg q.d. MOTHER | 0 of 22 |
| ATV/RTV 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. INFANT | 0 of 38 |
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 |
|---|---|
| ABC 300mg b.i.d. MOTHER | 21 of 26 |
| ATV/COBI 300/150 mg q.d. INFANT | 9 of 12 |
| ATV/COBI 300/150 mg q.d. MOTHER | 11 of 12 |
| ATV/RTV 300/100mg q.d. INFANT | 8 of 22 |
| ATV/RTV 300/100mg q.d. MOTHER | 21 of 22 |
| ATV/RTV 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. INFANT | 23 of 38 |
Most frequent serious adverse event terms
| Event term | Organ system | ABC 300mg b.i.d. MOTHER | ATV/COBI 300/150 mg q.d. INFANT | ATV/COBI 300/150 mg q.d. MOTHER | ATV/RTV 300/100mg q.d. INFANT | ATV/RTV 300/100mg q.d. MOTHER | ATV/RTV 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. INFANT |
|---|---|---|---|---|---|---|---|
| Cryptorchism | Congenital, familial and genetic disorders | 0 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 2 of 38 |
| Hyperbilirubinaemia | Hepatobiliary disorders | 0 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 2 of 38 |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | 0 of 26 | 2 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 0 of 38 |
| Dysmorphism | Congenital, familial and genetic disorders | 0 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 1 of 38 |
| Laryngomalacia | Congenital, familial and genetic disorders | 0 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 1 of 38 |
| Aspartate aminotransferase increased | Investigations | 0 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 1 of 22 | 0 of 38 |
| Haemangioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 1 of 38 |
| Neonatal seizure | Nervous system disorders | 0 of 26 | 1 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 0 of 38 |
| Pre-eclampsia | Pregnancy, puerperium and perinatal conditions | 0 of 26 | 0 of 12 | 1 of 12 | 0 of 22 | 0 of 22 | 0 of 38 |
| Premature baby | Pregnancy, puerperium and perinatal conditions | 0 of 26 | 1 of 12 | 0 of 12 | 0 of 22 | 0 of 22 | 0 of 38 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ABC 300mg b.i.d. MOTHER | ATV/COBI 300/150 mg q.d. INFANT | ATV/COBI 300/150 mg q.d. MOTHER | ATV/RTV 300/100mg q.d. INFANT | ATV/RTV 300/100mg q.d. MOTHER | ATV/RTV 300/100mg q.d. Then 400/100mg q.d. Then 300/100mg q.d. INFANT |
|---|---|---|---|---|---|---|---|
| Blood bilirubin increased | Investigations | 4 of 26 | 3 of 12 | 4 of 12 | 3 of 22 | 18 of 22 | 2 of 38 |
| Haemoglobin decreased | Investigations | 6 of 26 | 2 of 12 | 3 of 12 | 0 of 22 | 5 of 22 | 9 of 38 |
| Blood sodium decreased | Investigations | 10 of 26 | 0 of 12 | 2 of 12 | 0 of 22 | 12 of 22 | 0 of 38 |
| Blood glucose decreased | Investigations | 3 of 26 | 3 of 12 | 0 of 12 | 0 of 22 | 10 of 22 | 4 of 38 |
| Blood alkaline phosphatase increased | Investigations | 6 of 26 | 0 of 12 | 2 of 12 | 0 of 22 | 10 of 22 | 0 of 38 |
| Blood calcium decreased | Investigations | 9 of 26 | 0 of 12 | 2 of 12 | 0 of 22 | 6 of 22 | 0 of 38 |
| Jaundice neonatal | Pregnancy, puerperium and perinatal conditions | 0 of 26 | 2 of 12 | 0 of 12 | 1 of 22 | 0 of 22 | 14 of 38 |
| Amylase increased | Investigations | 3 of 26 | 0 of 12 | 0 of 12 | 0 of 22 | 9 of 22 | 0 of 38 |
| Aspartate aminotransferase increased | Investigations | 2 of 26 | 0 of 12 | 2 of 12 | 1 of 22 | 2 of 22 | 5 of 38 |
| Blood glucose increased | Investigations | 3 of 26 | 0 of 12 | 1 of 12 | 0 of 22 | 7 of 22 | 0 of 38 |
Serious events with the highest arm-level rate: cerebral palsy (50.0%), hypoxic-ischaemic encephalopathy (50.0%), premature baby (50.0%), kidney duplex (16.7%), umbilical hernia (16.7%).
The registry reports serious adverse events, other adverse events, and deaths separately for maternal and infant groups defined by regimen. The figures are group-level counts: the number affected is listed alongside the number at risk for that group. They should be read within each listed group, not pooled across regimens or interpreted as a randomized comparison. Because the arms include different drugs, populations, and circumstances, raw counts cannot isolate a drug effect.
For example, the ATV/COBI 300/150 mg q.d. mother group lists 3 serious adverse events among 12 at risk, while the corresponding infant group also lists 3 among 12 at risk. The DRV/RTV 600/100mg b.i.d. infant group lists 1 death, and its mother group lists none. Other infant groups with deaths include EFV 600mg q.d. and at least one 1st line TB drug, with 1; LPV/RTV 400/100mg b.i.d. then 600/150mg b.i.d. then 400/100mg b.i.d. at African sites, with 1; and no ARVs and at least two 1st line TB drugs, with 2. These are separate group records, not estimates of comparative risk.
Seriousness is distinct from the count of other adverse events. The record does not provide an adjusted comparison, a causal attribution, or enough context to combine these groups into an overall treatment estimate. The listed counts describe reported events and should not be used alone to judge a regimen’s safety.
12. What the Result Does, and Does Not, Mean
The study addresses an important measurement question: how antiretroviral and tuberculosis drug concentrations and pharmacokinetic parameters are characterized during pregnancy and postpartum. Its primary endpoint, median AUC12 with interquartile range, provides a summary of drug exposure over the specified sampling interval. The study also includes infant and postpartum contraceptive assessments. This scope is reflected in the many drug regimens and outcome measures recorded.
The registry entries do not include numerical AUC12 estimates or interquartile ranges. As a result, they do not establish whether exposure increased or decreased over a particular period, how large a change might have been, or how precisely such a change was estimated. Those findings are not reported in the registry record. The endpoint definition explains what was measured, but it is not a substitute for the outcome results.
Even with numerical pharmacokinetic summaries, interpretation would need to account for the study’s design. It was not a randomized comparison, and allocation was not stated. The arms are heterogeneous and do not form a common control comparison. Differences among them cannot be attributed to the drug alone from these registry entries. The assessment windows vary by arm, and participants were not expected to contribute measurements at every period.
The pharmacokinetic outcome is also distinct from a clinical endpoint. As a general concept, an exposure measure describes concentration over time; it does not by itself demonstrate a health benefit, harm, or treatment effectiveness. The registry does not identify a clinical target for AUC12 or report a link between the AUC12 measurements and clinical outcomes in the registry record for this analysis.
The safety counts describe reported events within regimen-specific maternal and infant groups. They are useful for understanding what the registry records, but they do not provide a controlled comparison or causal assessment. The defensible conclusion is therefore about the nature and scope of the measurements and the limitations of their interpretation, not about whether a particular treatment works or does not work.
13. Why This Trial Matters Statistically
Pregnancy and postpartum involve distinct assessment periods, and the registry records pharmacokinetic measurements across these periods for a wide range of antiretroviral and tuberculosis drugs. Statistically, this creates challenges beyond calculating an exposure summary. Researchers must define which participants contribute to each period, how measurements taken at different times are compared, and how the variability of drug concentrations is represented. The record’s use of medians and interquartile ranges makes the outcome’s distributional summary explicit.
The study also illustrates why a detailed analysis population matters. Participants could enter at different times and were not expected to have results at every period. A change in a period-specific summary could reflect a change within participants, a difference in who contributed data, or both. Without period-specific sample counts and the analysis method, readers cannot determine from the registry record how these possibilities were addressed.
The many regimens and outcomes make multiplicity and careful interpretation relevant. The registry lists 43 outcome measures and 126 analyses, but does not report a multiplicity procedure or a confirmatory hierarchy. Readers should distinguish the breadth of descriptive measurement from evidence in a single, prespecified comparison.
Finally, the study demonstrates that pharmacokinetic endpoints answer a different question from clinical outcome endpoints. AUC12 describes measured exposure, calculated from concentration-time profiles. It can characterize drug exposure, but clinical meaning depends on additional context, such as a relevant target or relationship with clinical outcomes, which is not reported in the registry record. The distinction is especially important when a study has no randomized comparator and its groups are not like-for-like.
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 principal limitation for interpreting the primary endpoint is that the registry record does not report numerical AUC12 medians or interquartile ranges. The definition and calculation method are described, but there is no outcome estimate in the registry record for this analysis. The size, direction, and precision of pharmacokinetic differences therefore cannot be assessed.
The design is not a randomized comparison, and allocation is not stated. The many arms cover different drugs, dosing regimens, populations, and settings. Comparisons between them may be confounded by these differences and are not equivalent to randomized treatment contrasts. The registry does not describe adjustment methods or a complete analysis model.
Timing and participant availability also vary. Measurements are described for the 2nd trimester, the 3rd trimester, and postpartum periods that differ by arm. Participants could enter at different periods and were not expected to have results at every period. Period-specific sample counts, reasons for absent measurements, and missing-data procedures are not reported in the registry record. The record also does not clarify whether period comparisons used the same participants.
The broad set of outcomes and analyses adds interpretive complexity. A multiplicity strategy and outcome hierarchy are not reported in the registry record. The study’s protocol-level sample-size justification, interim analyses, and full statistical analysis plan are also not reported in the registry record. Safety counts are presented by group and do not support a pooled or causal comparison. These limitations concern what can be concluded from the registry information; they do not establish that relevant procedures were not used in the study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy — NCT00042289.
- Registry record last updated 2025-12-02; status last verified 2025-11.
- Results first posted 2022-07-22.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT00042289 is a completed prospective Phase IV pharmacokinetic study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The registry reports enrollment of 1578, a start date of 2003-06-09, and a primary completion date of 2020-09-30. The study evaluated antiretroviral and tuberculosis drug pharmacokinetics in pregnant women and infants, as well as certain postpartum antiretroviral assessments before and after hormonal contraceptive use.
The primary outcome was median AUC12 with interquartile range, calculated from plasma concentration-time profiles using noncompartmental methods and the linear trapezoidal rule. Numerical primary-outcome estimates are not reported in the registry record. The registry lists 43 outcome measures and 126 analyses, and reports safety counts by maternal and infant regimen groups. It identifies the study as not randomized, with allocation not stated; the listed arms are not a like-for-like control comparison.