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 Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya (NCT00428116), a randomized na study. The primary outcome is Growth at 18 Months Post-randomization.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00428116 |
| Phase | NA |
| Condition | HIV Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 140 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Washington |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns infants with HIV-1 who began HAART before 13 months of age. The registry summary describes treatment for 24 months before considering randomization among infants with immune reconstitution and adequate growth. It refers to approximately 100 infants who might meet those criteria, while the registered enrollment is 140. These figures describe different aspects of the record and do not establish how many infants were ultimately randomized or analyzed.
Intervention
In the interrupted-HAART arm, eligible infants were to stop HAART after the initial 24 months of treatment and be followed for 18 months. The registry summary presents treatment interruption as an approach to be evaluated against continued treatment. It does not report enough detail to establish how interruption, restarting therapy, or other treatment decisions were managed during follow-up.
Comparator
The continued-HAART arm was to receive HAART for 18 months after randomization. The two arms were assigned in a randomized, parallel design, and masking was listed as none. The record does not report the sequence-generation method or other details about how assignment was implemented.
Primary question
The primary outcome is titled growth at 18 months post-randomization. Weight and height are transformed into weight-for-age and height-for-age Z-scores using World Health Organization Child Growth Standards, accounting for age and gender. The statistical question is how those growth measures compare between continued and interrupted treatment at the stated follow-up. The registry record does not report a single summarized comparison of the growth outcomes, so it does not establish the direction or precision of any between-arm difference.
3. Trial Design
This was a randomized, parallel-group study of pediatric HIV-1 treatment in Nairobi, Kenya. The registry lists no masking, so the comparison was open-label. The phase is recorded as not applicable. The sponsor is the University of Washington. The registered enrollment is 140, and the study status is terminated. The record lists a start date of 2007-09 and primary completion in 2013-07; it does not give a reason for termination in the registry record for this description.
The planned treatment sequence began with HAART in infants who started therapy before 13 months of age. The registry summary describes 24 months of initial HAART, followed by randomization of infants who had immune reconstitution and adequate growth to either continued or interrupted treatment. It estimates that approximately 100 might qualify, but this is a planning description, not a reported randomized or analyzed sample size. The registered enrollment of 140 should not be treated as the number randomized to the two comparison arms.
After randomization, the arm descriptions specify 18 months of follow-up: one group continued HAART, while the other interrupted treatment. Growth at that follow-up is the primary outcome. Morbidity is listed as a secondary outcome. The record does not provide the full protocol, detailed eligibility criteria, the randomization procedure, or the number assigned to each arm for the primary analysis. Safety summaries list 21 participants at risk in each arm, but those figures alone do not establish the analysis population for growth or morbidity.
The status “terminated” describes the recorded study status; the registry record does not state why the study ended or whether termination affected follow-up, outcome collection, or planned analyses. Those details are important when interpreting the completeness of the results, but cannot be inferred from the design description alone.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Of 140 infants enrolled, 37 infants died, 11 were lost, and 7 were withdrawn. Of 75 infants who completed 2 years ART pre-randomization, 33 were ineligible for randomization and 42 were randomized.
Overall Study
| Stage | Continued HAART | Interrupted HAART |
|---|---|---|
| STARTED | 21 | 21 |
| COMPLETED | 18 | 21 |
| NOT COMPLETED | 3 | 0 |
Reasons for not completing this period:
| Reason | Continued HAART | Interrupted HAART |
|---|---|---|
| Death | 1 | 0 |
| Withdrawal by Subject | 1 | 0 |
| Lost to Follow-up | 1 | 0 |
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: following 24 months of HAART
| Characteristic | Unit | Continued HAART | Interrupted HAART | Total |
|---|---|---|---|---|
| Participants analysed | 21 | 21 | 42 | |
| Age, Categorical: <=18 years | Participants | 21 | 21 | 42 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | months | 29 (28.8 to 33.8) | 30.0 (29.3 to 34.9) | 30.0 (28.9 to 34.6) |
| Sex: Female, Male: Female | Participants | 15 | 8 | 23 |
| Sex: Female, Male: Male | Participants | 6 | 13 | 19 |
| Region of Enrollment: Kenya | participants | 21 | 21 | 42 |
| CD4% | percent | 33 (30 to 40) | 34 (32 to 38) | 33 (30 to 39) |
| Log10 HIV RNA level | copies/ml | 2.18 (2.18 to 2.64) | 2.18 (2.18 to 2.71) | 2.18 (2.18 to 2.71) |
6. Primary Endpoint
The registry lists the primary outcome as Growth at 18 Months Post-randomization, measured over 18 months of post-randomization follow-up.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | z-score |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is growth at 18 months after randomization. The registry describes transforming weight and height into two age- and gender-referenced measures: weight-for-age Z-score (WAZ) and height-for-age Z-score (HAZ), using World Health Organization Child Growth Standards. A Z-score expresses a measurement relative to a reference distribution for the relevant age and gender. In general, such standardized measures make growth observations easier to compare across children at different ages than raw weight or height alone.
The endpoint is reported as a median with an inter-quartile range. In general, the median describes the central observation in an ordered set of values, while the inter-quartile range describes the span containing the middle half of those observations. These summaries can describe the distribution without requiring it to be symmetric, but they do not by themselves quantify the uncertainty in a between-arm contrast. The registry record does not report the actual WAZ or HAZ summaries, a contrast between arms, a confidence interval, or a statistical test in a form that reduces the primary outcome to one comparison. The specific growth results therefore cannot be interpreted from the posted record as a single estimated treatment difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question the study was designed to address: whether growth after randomization differed between infants assigned to continued HAART and infants assigned to interrupt treatment after an initial treatment period. It does not establish the answer. Although growth at 18 months post-randomization is identified as the primary outcome, the outcome includes weight-for-age and height-for-age Z-scores, and the primary outcome is not reduced to one comparison in the posted results. No arm-level growth summaries or between-arm estimates are available in the record details.
That absence limits both the direction and the precision of interpretation. Without the reported medians and inter-quartile ranges, readers cannot tell how the observed growth distributions were situated in either arm. Without a between-arm estimate and its uncertainty, readers cannot judge how compatible the results are with different possible differences. In general, a confidence interval gives a range of values compatible with the data and the analysis assumptions; it conveys precision, not a guarantee that the true effect lies within the interval. No confidence interval for the primary growth comparison is reported in the registry record.
The registry lists seven analyses and two outcome measures, but does not specify how those analyses map to outcomes, time points, or statistical tests. It also does not report whether estimates were adjusted, which analysis population was used, or how missing follow-up measurements were handled. These omissions prevent a reader from assessing whether the posted analyses reflect the planned primary analysis or how sensitive results might be to analytic choices. They also make it impossible to evaluate the handling of multiple comparisons from the registry information alone.
The safety summaries are a separate source of descriptive information. For serious adverse events, the registry lists 2 affected participants among 21 at risk in the continued-HAART arm and 1 among 21 at risk in the interrupted-HAART arm. Those counts do not establish a causal safety difference. The record also lists serious-event terms with percentages, but does not specify the denominator or explain how those terms relate to the affected-participant counts. The death count is not reported in the registry record.
Any sample-size illustrations based on an observed effect should be read as planning exercises, not as evidence that the trial had a particular probability of detecting an effect. The stated illustration assumptions include two-sided significance level 0.05, equal allocation, and a normal approximation. Such calculations depend on the effect chosen and assumptions about the analysis; they are not a substitute for the observed estimates and their uncertainty. The trial’s own sample-size justification is not reported in the registry record.
Overall, the record supports a description of the randomized design, the intended growth measures, and selected safety counts. It does not support a conclusion about the comparative growth results, nor does the information presented establish whether treatment interruption was beneficial, harmful, or equivalent on the primary outcome.
9. Statistical Methods Explained
The statistical information in the registry record is enough to identify the broad comparison and the form of the primary growth outcome, but not enough to reconstruct the analysis. In general, methods should connect the design, outcome definition, analysis population, model or summary measure, and uncertainty estimate. Several of those details are not reported in the registry record, so the distinctions below are important when reading the posted results.
What does randomization contribute?
Random assignment is intended to make the treatment groups comparable, on average, with respect to measured and unmeasured characteristics at the point of assignment. A parallel design means participants are assigned to one arm for the comparison rather than crossing between treatment conditions as part of the design. Here, the registry identifies random allocation, a parallel model, and no masking. Randomization does not guarantee that groups will be identical, especially when the number actually randomized is not reported. The sequence-generation and allocation-concealment procedures are not reported in the registry record, so their implementation cannot be assessed.
Masking is listed as none. In general, lack of masking can matter for outcomes influenced by knowledge of treatment assignment, including clinical decisions, reporting, or measurement practices. Growth measurements are more concrete than subjective reports, but the record does not describe measurement procedures or safeguards against differences in assessment. This does not establish that measurement bias occurred; it identifies a design feature readers may consider.
How should the growth summaries be read?
The primary outcome uses WAZ and HAZ, derived from weight and height with reference to age and gender. These standardized measures allow growth to be described relative to the World Health Organization Child Growth Standards. The registry specifies the median and inter-quartile range as the summary format. In general, the median is less sensitive than the mean to unusually high or low observations, and the inter-quartile range conveys spread in the central portion of the data. Neither summary alone is a direct estimate of the difference between randomized arms.
A comparison might be expressed as a difference in medians, another contrast between distributions, or an estimate from a statistical model. The registry record does not report which inferential method was used for the primary outcome, whether the comparison was adjusted for baseline measurements, or what uncertainty measure accompanied it. It is therefore not appropriate to infer a test, model, or adjusted effect from the outcome description alone.
What do confidence intervals and p-values ordinarily add?
In general, a confidence interval describes the precision of an estimated effect under the chosen analysis and its assumptions. A narrow interval indicates greater precision than a wide one, while an interval spanning values on both sides of no difference may be compatible with several interpretations. A p-value, when reported, measures how unusual data at least as extreme as those observed would be under a specified null hypothesis and analysis model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not report a primary growth estimate, confidence interval, or p-value in a single comparison that can be interpreted for this outcome.
Why do over-dispersion and distributional assumptions matter?
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If a model assumes less variability than the data contain, standard errors can be too small and uncertainty can be understated. The choice of model should reflect the outcome type and its distribution. The registry identifies continuous growth Z-scores summarized by medians and inter-quartile ranges, but it does not report a model for them. There is consequently no basis for claiming that over-dispersion was present or that a particular correction was used in this trial.
The stated sample-size illustration uses a normal approximation, equal allocation, a two-sided significance level of 0.05, and an effect defined as a stated fraction of the observed effect. These are assumptions for a planning illustration, not reported design justifications. In general, sample-size planning depends on the target effect, variability, chosen error rates, allocation, and analysis method. If an illustration uses a fraction of an observed effect, it explores a hypothetical target rather than documenting the trial’s original design or its achieved power. The trial’s own sample-size justification and numerical design assumptions are not reported in the registry record.
What can the analysis count tell us?
The registry record identifies seven analyses and two outcome measures, but does not explain the mapping among analyses, outcomes, and time points. A count does not identify whether analyses are separate tests, subgroup comparisons, repeated time-point summaries, or alternative models. Nor does it establish which analysis was designated primary. The result presentation does not reduce the growth outcome’s several categories or time points to one comparison. Readers should therefore avoid treating any isolated estimate as the definitive primary result without a documented analysis plan.
In general, recalculation from published summary statistics can be useful as a descriptive check, but an unadjusted recalculation may differ from a sponsor’s prespecified analysis because it can omit covariate adjustment, account for participants differently, or use a different statistical method. No recalculated primary growth comparison is available in the registry information. If a discrepancy between a sponsor analysis and a simple recalculation were documented, the sponsor’s own analysis would take precedence for reporting the trial’s analysis, while the recalculation would remain a limited check rather than a replacement.
How should sample-size illustrations be interpreted?
Sample-size calculations describe how many participants or events a hypothetical study would need under specified assumptions to target a chosen power and significance level. They are planning illustrations, not observed outcomes and not “observed power.” The listed assumptions identify a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect is framed as a stated fraction of the observed effect. The record does not include the numerical illustrations in the registry record, and those assumptions do not establish the trial’s original design plan. Any illustration should be understood as conditional on its assumptions, not as evidence that the trial was adequately powered or that a treatment effect was established.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies seven analyses and two outcome measures, while the primary growth outcome involves both weight-for-age and height-for-age Z-scores and is not reduced to one comparison. Morbidity is listed as a secondary outcome. This creates the possibility of multiple outcomes, measures, or analyses, but the registry record does not explain how the analyses are related or which comparisons were considered primary, secondary, or exploratory.
In general, when many statistical comparisons are made, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiplicity. Common approaches include defining a hierarchy of outcomes, adjusting significance thresholds, or emphasizing estimation and uncertainty rather than a collection of isolated p-values. The registry record does not report a multiplicity strategy, a prespecified testing hierarchy, or an adjustment method. It is therefore not possible to determine from the record whether and how multiplicity was addressed.
Missing data and analysis populations are also insufficiently described. The record does not state how many participants had growth measurements at 18 months, how missing outcomes were handled, whether participants were analyzed according to assigned arm, or whether any per-protocol or other population was used. In general, incomplete follow-up can affect comparability if missingness differs between groups or is related to outcome. This is a concern to evaluate, not evidence that missing data caused bias in this study.
The registry enrollment is 140, while the study summary refers to 150 infants initially and approximately 100 potentially eligible for randomization after treatment and eligibility assessment. The record does not reconcile these figures or report the final randomized and analyzed counts for the primary outcome. The reason for the terminated status is also not reported in the registry record. Together, these gaps restrict assessment of multiplicity, attrition, and the population represented by the results.
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 |
|---|---|---|---|
| Continued HAART | 2 | 21 | 9.5% |
| Interrupted HAART | 1 | 21 | 4.8% |
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 |
|---|---|
| Continued HAART | 21 of 21 |
| Interrupted HAART | 21 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | Continued HAART | Interrupted HAART |
|---|---|---|---|
| Hepatotoxicity | Hepatobiliary disorders | 1 of 21 | 1 of 21 |
| Death | Infections and infestations | 1 of 21 | 0 of 21 |
| Cellulitis | Skin and subcutaneous tissue disorders | 0 of 21 | 1 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Continued HAART | Interrupted HAART |
|---|---|---|---|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | 21 of 21 | 20 of 21 |
| Anemia | Blood and lymphatic system disorders | 12 of 21 | 16 of 21 |
| Rash | Skin and subcutaneous tissue disorders | 11 of 21 | 11 of 21 |
| Diarrhea | Gastrointestinal disorders | 7 of 21 | 12 of 21 |
| Lymphadenopathy | Blood and lymphatic system disorders | 5 of 21 | 14 of 21 |
| High cholesterol | Metabolism and nutrition disorders | 10 of 21 | 4 of 21 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 4 of 21 | 3 of 21 |
Serious events with the highest arm-level rate: death (4.8%), hepatotoxicity (4.8%), cellulitis (4.8%).
The registry safety summaries list 21 participants at risk in each arm. In the continued-HAART arm, 2 participants are recorded as affected by serious adverse events; in the interrupted-HAART arm, 1 participant is recorded as affected. These are descriptive counts. The registry information does not provide an uncertainty estimate or a formal comparison, so the counts alone do not establish a difference in safety between treatment strategies.
The record also lists Death, Hepatotoxicity, and Cellulitis among the top serious-event terms, each with a reported value of 4.8%. The denominator and counting rules for these percentages are not specified in the registry record. They should not be assumed to use the same denominator as the arm-level “affected” counts, nor should they be added together. The death count is not reported in the registry record, despite Death appearing as a serious-event term.
For other adverse events, 21 participants are listed as affected among 21 at risk in each arm. The registry summary does not provide further detail about event types, severity, timing, recurrence, or attribution. It also does not state whether events were considered related to treatment. In general, adverse-event summaries describe events observed during follow-up and do not by themselves show that a treatment caused them. These safety figures should be interpreted as registry descriptions, not as a complete assessment of comparative risk.
12. What the Result Does, and Does Not, Mean
The study addresses a consequential statistical question: how growth outcomes compare after randomization to continued or interrupted HAART in infants who had already received initial treatment and met the described eligibility conditions. Its randomized, parallel design is relevant to that comparison. The primary outcome is defined using age- and gender-standardized measures of weight and height at 18 months post-randomization, and the record also lists morbidity as a secondary outcome.
However, the registry information does not report a single primary growth comparison or the underlying arm-level growth summaries. There is no reported direction or magnitude of a growth contrast, and no uncertainty interval in the available outcome description. Consequently, the record does not establish whether growth differed between groups, how precisely any difference was estimated, or whether results were compatible with a range of effects. It also does not support a conclusion that either strategy was superior, equivalent, safe, or harmful.
The safety counts add descriptive information but have important limits. The arm-level serious adverse-event counts are based on 21 participants at risk in each group, and the listed serious-event percentages have no stated denominator in the record. The number of deaths is not reported. These summaries do not substitute for a detailed account of adverse-event definitions, follow-up, severity, treatment attribution, or comparative analysis.
The registry describes a terminated study, but does not give the reason. Nor does it reconcile registered enrollment of 140 with the summary’s references to 150 initial infants and approximately 100 potentially eligible for randomization. The number randomized and the number analyzed for growth are not reported in the information available. These uncertainties matter because the design’s target population and the observed analysis population may differ.
In general, a randomized design can strengthen causal interpretation when allocation, follow-up, outcome measurement, and analysis are adequately documented. Here, the registry supports understanding of the intended design and endpoint, but not a substantive estimate of the primary comparison. The appropriate interpretation is therefore limited: the study planned to compare these strategies on growth and morbidity, while the posted information does not establish the comparative growth result.
13. Why This Trial Matters Statistically
This trial is statistically notable because its design separates an initial period of treatment from a later randomized comparison. The question is not simply whether infants received HAART; it concerns the comparison of continued treatment with interruption after an initial treatment phase and among infants described as eligible for randomization. That distinction defines the population to which any randomized comparison would apply. The registered enrollment does not itself indicate how many infants reached randomization or contributed outcome data.
The primary outcome also illustrates why outcome definition matters. Weight and height are expressed as separate age- and gender-standardized Z-scores, and the registry specifies medians and inter-quartile ranges. Those choices shape what the summary describes: central location and spread for growth measures, rather than a single overall clinical outcome. Since the record does not reduce the growth outcome to one comparison, it is not possible to connect the endpoint definition to a reported comparative estimate.
The record’s analysis gaps show why trial interpretation requires more than knowing allocation and follow-up duration. The analysis population, handling of missing outcomes, inferential method, uncertainty estimates, and multiplicity approach are not reported. Without these details, readers cannot evaluate the precision and robustness of the primary comparison or determine how the seven listed analyses relate to the outcome measures.
Finally, the safety summaries demonstrate the difference between event counts and comparative evidence. Counts of affected participants and percentages attached to serious-event terms are informative descriptions, but denominators, attribution, and uncertainty are needed for fuller interpretation. Statistically, the value of the record lies in clarifying the intended randomized question and identifying what outcome and safety information is recorded, while also exposing limits in the results documentation. It does not furnish the growth estimate needed to answer that question.
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 limitations specific to this trial restrict interpretation of the registry information. The study status is terminated, but the reason for termination is not reported in the registry record. Without that context, readers cannot determine whether termination affected enrollment, planned follow-up, completeness of outcome collection, or the analysis strategy.
The enrollment and population descriptions are not reconciled. Registered enrollment is 140, while the brief summary refers to 150 infants who initiated HAART and approximately 100 who might meet the criteria for randomization after 24 months. These descriptions should not be treated as interchangeable counts. The final number randomized and the number contributing primary growth data are not reported in the information available.
The primary outcome is described as growth at 18 months, with weight-for-age and height-for-age Z-scores, but no arm-level values or single between-arm comparison are reported. The analysis method, uncertainty estimates, and any adjustment for baseline growth are not reported. Nor are the handling of missing measurements, analysis population, or approach to the multiple analyses described. These omissions prevent evaluation of precision, attrition, and analytic robustness.
The safety information is also limited. The registry lists serious adverse-event counts and selected event terms, but does not report the denominator for the listed percentages, a death count, event timing, attribution, or comparative uncertainty. The general study summary mentions external monitoring, but details of oversight and any monitoring decisions are not reported in the registry record.
These limitations do not show that the study was conducted improperly or that bias occurred. They indicate that the posted registry information is insufficient to assess the primary result and several important aspects of follow-up and analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya — NCT00428116.
- Registry record last updated 2018-07-26; status last verified 2018-06.
- Results first posted 2015-08-20.
- 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
The registry record describes a randomized, open-label, parallel-group study of pediatric HIV-1 treatment in Nairobi, Kenya, sponsored by the University of Washington. It lists enrollment of 140, a start date of 2007-09, primary completion in 2013-07, and status terminated. The study summary describes an initial HAART period followed by randomization of eligible infants to continued or interrupted treatment for 18 months.
The primary outcome is growth at 18 months post-randomization, measured using weight-for-age and height-for-age Z-scores and summarized by medians and inter-quartile ranges. Morbidity is listed as a secondary outcome. The record does not report a single comparative growth result, analysis population, missing-data method, or multiplicity plan. Safety summaries list serious adverse events in both arms, but the death count and denominators for selected serious-event percentages are not reported. The reason for termination is also not reported in the registry record.