Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV-Infected Infants, Children, and Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV-Infected Infants, Children, and Adolescents (NCT00006604), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants Who Experienced a Safety Endpoint of Interest Attributed to ATV.

2. Clinical Question

The study’s stated purpose was to identify safe and tolerable doses of ATV, with or without a low-dose RTV boost, when used with other anti-HIV drugs. It included ART-naive and ART-experienced participants according to its official title. The registry record describes dose groups by age, formulation, and whether RTV was included; the treatment was not assigned through randomization.

The clinical question is therefore principally a dose-finding and safety question, rather than a comparison of ATV against an untreated or randomized control group. The record also lists virologic response and changes in CD4 count and CD4 percent as secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record.

3. Trial Design

This was a Phase I/II, open-label, non-randomized, parallel-group study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It enrolled 195 participants and is listed as completed. The recorded study start was 2000-11, and primary completion was 2011-10. The registry record does not report a masking procedure; the study is identified as having no masking.

Participants were enrolled into groups defined by age, ATV formulation, dose, and use or non-use of RTV. Groups 1 and 2 received ATV powder with two NRTIs, at tested doses of 310 mg/m^2 and 620 mg/m^2; a final dose was not established for those groups. Group 3 received ATV capsule with two NRTIs, with a final dose of 520 mg/m^2. Group 4 received ATV capsule with two NRTIs, with a final dose of 620 mg/m^2.

Groups 5, 5a, and 6 received ATV powder with RTV and two NRTIs, at a final dose of 310 mg/m^2. Groups 7 and 8 received ATV capsule with RTV and two NRTIs, at a final dose of 205 mg/m^2. The age bands differ across groups, including a separate group for participants between 91 days and 180 days of age. These group distinctions matter when reading results: the regimens and participant ages were not held constant across groups.

Because allocation was non-randomized and there was no masking, the arm results do not represent a randomized head-to-head comparison. The registry record does not report the allocation procedure, a protocol-level statistical analysis plan, or a sample-size justification. Those details should not be inferred from the design description or enrollment total.

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 17 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients accrued at the final recommended dose for each group.

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: Participants accrued and treated at the dose ultimately selected for their groups. NOTE: (1) Final Dose not established for Grps 1, 2; (2) Grp 5a started with n=12, but (1) participant inadvertently enrolled,never received ATV, final n=11; (3) Grp 8 started with n=15, but (1) participant inadvertently enrolled, never received ATV, final n=14.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced a Safety Endpoint of Interest Attributed to ATV, measured over From study entry up to week 96.

The primary endpoint counts participants who experienced a safety endpoint of interest attributed to ATV. Its timeframe runs from study entry up to week 96. The primary endpoint population is described as patients accrued at the final recommended dose for each group, rather than all enrolled participants as one undifferentiated population.

The endpoint combines several types of safety events: Total Bilirubin at least 5.1xULN, ECG events, and other Grade 3+ toxicities attributed to study treatment. The registry describes clinician grading according to the Division of AIDS (DAIDS) Toxicity Table: Grade 1 was mild, Grade 2 moderate, Grade 3 severe, Grade 4 potentially life-threatening, and Grade 5 death. The study team determined whether an event was related to study treatment.

General statistical context: a participant-count endpoint can make a safety summary easier to interpret as the number of people meeting a defined event criterion. Here, however, the composite combines laboratory, ECG, and toxicity events that can differ in nature and seriousness. A count alone does not describe the timing, duration, recurrence, or clinical course of events. The registry record does not report the primary endpoint result, so the number of participants meeting this definition is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is identified as non-randomized and parallel. In a parallel study, participants are assigned to one group rather than crossing through each regimen, but the registry does not report a randomized assignment process. General statistical context: randomization is used to balance measured and unmeasured participant characteristics on average across comparison groups. Without randomization, group differences can reflect participant composition, regimen differences, or other factors as well as treatment. The record cautions that the arms are not like-for-like control comparisons.

What does the primary endpoint count?

The primary endpoint is a participant count for safety events attributed to ATV. It includes Total Bilirubin at least 5.1xULN, ECG events, and other Grade 3+ toxicities, with the observation period stated as study entry up to week 96. The endpoint population is patients accrued at the final recommended dose for each group. The registry provides this definition but does not report the resulting number of participants meeting the endpoint.

General statistical context: a participant count is different from an event count. One participant may experience more than one event, while a count of participants meeting an endpoint ordinarily records whether each person met the criterion. The posted record calls the primary outcome a number of participants, but it does not provide event-level timing or recurrence details. The serious and other adverse-event figures are separate listed summaries and should not be assumed to reproduce the primary endpoint.

How should the toxicity grades be understood?

The registry says clinicians graded adverse events using the DAIDS Toxicity Table. Grade 1 is mild, Grade 2 moderate, Grade 3 severe, Grade 4 potentially life-threatening, and Grade 5 death. The relationship to study treatment was determined by the study team. These definitions explain the grading framework; they do not indicate how many primary endpoint events occurred. That result is not reported in the registry record.

What can the group counts establish?

The adverse-event summaries give group-specific numbers at risk and affected. For serious adverse events, the counts are reported as 10 of 21 for Group 3, 15 of 25 for Group 4, 12 of 21 for Group 5, 14 of 26 for Group 6, 15 of 24 for Group 7, 8 of 14 for Group 8, and 5 of 11 for Group 5A. For other adverse events, the affected count equals the at-risk count in every listed group. The record does not describe these group counts as randomized comparisons or provide an adjustment model.

General statistical context: counts can describe what was recorded in a group, but comparisons require attention to group definitions, follow-up, event definitions, and uncertainty. Here, the age bands and regimens vary. The record does not report confidence intervals, hypothesis tests, or model-based estimates for these adverse-event counts. No new inferential conclusion should be attached to a difference between the listed counts.

What do the planning assumptions mean?

The sample-size material uses a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not a description of the trial’s own design; the record does not report a sample-size justification from the study protocol. Any sample sizes in such an illustration are planning quantities, not observed power.

General statistical context: power is a design property calculated under specified assumptions about an effect, variability, allocation, and analysis. It is not a retrospective measure of whether a completed study “had enough power.” When planning calculations use an observed effect, the illustration depends on that effect estimate and should not be mistaken for evidence that the trial detected a true effect. The registry record does not provide enough detail to reconstruct or validate the protocol’s planning decisions.

What statistical results are absent?

The registry lists 15 outcome measures and zero analyses. It does not report a statistical analysis plan, adjusted estimates, p-values, confidence intervals, interim analyses, or a detailed account of missing-data methods. These items are not reported in the registry record. General statistical context: over-dispersion matters when count data vary more than an assumed model allows, because standard errors and uncertainty estimates may then be too small if the model is not appropriate. The primary endpoint is described as a participant count, but the registry does not report a fitted count model or dispersion estimate. It is therefore not possible to determine whether an over-dispersion adjustment was considered or used.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary safety outcome and secondary outcomes covering HIV RNA thresholds at week 24, week 48, and week 96, and changes in CD4 count and CD4 percent at specified follow-up times. It lists zero analyses. The registry record does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment across outcomes and time points. It also does not report which outcomes were considered confirmatory or exploratory.

General statistical context: when many outcomes or time points are tested, the chance of at least one apparently notable result can increase if no plan accounts for the multiple comparisons. Without a reported analysis plan and numerical outcome analyses, the impact of multiplicity cannot be assessed for this study. No correction method should be presumed.

The record does not report how missing outcome observations were handled, how many participants contributed data at each follow-up time, or whether missingness differed among groups. The enrollment total of 195 is not, by itself, an analysis denominator for the primary endpoint or secondary outcomes. The primary population is described as participants accrued at the final recommended dose for each group, but the number in that population is not reported in the registry record.

The registry also does not report an analysis population definition beyond the primary endpoint population description, or whether any participants were excluded from particular analyses. These gaps limit interpretation of the completeness and comparability of outcome data. No assumptions about imputation, censoring, or participant exclusions can be drawn from the posted entry.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: blood bilirubin increased (41.7%), blood bilirubin unconjugated increased (37.5%), hyperbilirubinaemia (24.0%), blood alkaline phosphatase increased (18.2%), meningitis (9.1%).

The serious adverse-event summary reports the number at risk and the number affected for each listed group. In the order Group 3, Group 4, Group 5, Group 6, Group 7, Group 8, and Group 5A, the serious-event counts are 10 of 21, 15 of 25, 12 of 21, 14 of 26, 15 of 24, 8 of 14, and 5 of 11. The other-adverse-event affected counts are 21 of 21, 25 of 25, 21 of 21, 26 of 26, 24 of 24, 14 of 14, and 11 of 11, respectively.

These counts describe the registry’s categories and denominators; they are not randomized comparisons. The groups differ in regimen and age range, and the record cautions that they are not like-for-like controls. The deaths column is not populated in the posted summary, so death counts are not reported in the registry record.

The listed serious-event terms include Blood bilirubin increased (41.7%), Blood bilirubin unconjugated increased (37.5%), Hyperbilirubinaemia (24.0%), Blood alkaline phosphatase increased (18.2%), Meningitis (9.1%), and Electrocardiogram QT prolonged (9.1%). Term percentages do not, on their own, show the number of unique participants affected by each term or how events overlapped. The registry record does not provide those details.

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

The record describes a study designed to investigate ATV doses and safety in HIV-infected infants, children, and adolescents, including regimens with and without RTV. It documents distinct age- and formulation-based groups and provides adverse-event counts for several of those groups. This supports a descriptive account of the posted safety summaries and the study’s intended endpoint.

The record does not report the numerical result for the primary endpoint: the number of participants with an ATV-attributed safety event of interest among those accrued at each group’s final recommended dose. Nor does it report analyses, confidence intervals, p-values, or results for the listed secondary outcomes. Thus, the precision of the primary endpoint estimate and the statistical evidence for any between-group difference cannot be determined from the registry record.

The groups were non-randomized and varied in age range, formulation, dose, and use of RTV. Their adverse-event counts should not be treated as if they came from balanced randomized arms. The record itself notes that these are not like-for-like control comparisons. No conclusion that one regimen caused more or fewer events than another follows from the group counts alone.

General statistical context: a registry result is most informative when endpoint definitions, analysis populations, estimates, and measures of uncertainty are reported together. A safety count without the primary endpoint result or analytic detail leaves important questions unresolved, including how many participants met the endpoint and how precisely the count was estimated. The record also does not provide enough information to interpret missing observations or assess multiplicity across the many listed outcomes.

Accordingly, the posted entry establishes the study’s design and reported safety-count summaries, but not a definitive comparative treatment effect or a quantified estimate of primary endpoint risk. These limits describe the available registry information; they are not evidence for or against a regimen’s clinical effect.

13. Why This Trial Matters Statistically

This study illustrates why design details are central to statistical interpretation in clinical research. Although the registry lists several groups, the study was non-randomized, open-label, and organized around different age ranges, ATV formulations, doses, and the addition or absence of RTV. A set of arm-specific results is not automatically a comparative experiment. Without randomized, like-for-like groups, descriptive differences cannot be isolated as treatment effects.

The endpoint also illustrates the importance of matching a safety question to a complete result. It is defined as a participant count combining bilirubin, ECG, and other Grade 3+ toxicity criteria, attributed to ATV over a stated follow-up period. But the registry does not report the numerical primary endpoint result. The adverse-event summaries do not replace that missing result because their categories and definitions are not shown to be identical to the primary composite.

General statistical context: clinical interpretation depends not only on an observed estimate but also on the population analyzed, the outcome definition, and uncertainty around the estimate. Here, the record lists 15 outcome measures but zero analyses, and does not report confidence intervals or p-values. Consequently, readers cannot assess precision, multiplicity handling, or the statistical evidence for group comparisons from the registry entry.

The trial remains statistically informative as an example of the limits of registry summaries: design, regimen, endpoint, and denominator information can be useful, while missing outcome analyses constrain conclusions. Keeping those two aspects separate prevents descriptive safety counts from being overread as causal or comparative evidence.

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 is that the primary endpoint is defined but its result is not reported in the registry record. The record therefore does not state how many participants experienced the specified ATV-attributed safety endpoint in the primary endpoint population. The listed group adverse-event counts cannot be assumed to be equivalent to that composite.

The study was non-randomized, and its groups differed in age range, formulation, dose, and use of RTV. The registry explicitly says the arms are not a like-for-like control comparison. This limits interpretation of differences between group counts and prevents treating those differences as randomized treatment effects.

The entry lists 15 outcome measures and zero analyses. It does not report estimates or uncertainty measures for the primary outcome, a statistical analysis plan, multiplicity handling, missing-data methods, or analysis populations beyond the primary population description. The number of participants contributing to each outcome or follow-up time is not reported in the registry record. Death counts are also not reported in the posted adverse-event summary.

The registry does not report the study’s sample-size justification, interim analyses, or detailed protocol-level analysis decisions. Its planning illustration is not the trial’s design calculation and should not be read as observed power. These limitations are specific to the information in the registry entry; the record does not establish whether additional analyses or details exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV-Infected Infants, Children, and Adolescents — NCT00006604.
• Registry record last updated 2021-11-05; status last verified 2016-03.
• Results first posted 2016-04-05.
• 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

NCT00006604 is a completed, open-label, non-randomized Phase I/II parallel study sponsored by NIAID. It enrolled 195 HIV-infected infants, children, and adolescents. The recorded study start was 2000-11, and primary completion was 2011-10.

The study examined ATV with other anti-HIV drugs, with some groups also receiving RTV. Groups differed by age, formulation, dose, and regimen. The primary endpoint counted participants with specified ATV-attributed safety events from study entry up to week 96 among patients accrued at each group’s final recommended dose.

The registry lists adverse-event counts and secondary outcome definitions, but zero analyses. The numerical primary endpoint result, statistical comparisons, and measures of uncertainty are not reported in the registry record.