Heart Function in HIV-Negative Children Exposed to HIV and HAART: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Heart Function in HIV-Negative Children Exposed to HIV and HAART (NCT01107834), a registered phase not stated study. The primary outcome is Left Ventricular Mass Index.

2. Clinical Question

3. Trial Design

This completed study was registered as NCT01107834, with the title “Heart Function in HIV-Negative Children Exposed to HIV and HAART.” Its official title describes left ventricular function in HIV-negative children exposed to HIV and HAART in utero. Washington University School of Medicine is listed as the sponsor. The registry gives a start date of 2010-05 and a primary completion date of 2011-12. Enrollment is listed as 60.

The study compares two groups: HIV-negative children exposed to HIV and HAART in utero, and HIV-negative children born to healthy, HIV-negative women. The stated objective is to characterize heart function in the exposed children and compare it with age- and gender-matched healthy children. The record does not describe an assigned intervention. Allocation is not stated, and the registry explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The groups should therefore be understood as exposure-defined cohorts, not as treatment arms created by random assignment.

The primary measure is left ventricular mass index at baseline, obtained by 2D echocardiography. The record also lists secondary measures of global strain rate, systolic myocardial velocity during systole (S'), early-to-late diastolic filling ratio, and myocardial wall velocity during early diastole. It identifies six outcome measures and six analyses, but does not provide results for them in the registry record.

Important design details are not reported in the registry record. These include the method of recruitment, eligibility criteria, how age and gender matching was implemented, whether echocardiograms were assessed with blinding, and the analysis plan. The registry status is completed, but that status alone does not show that every planned assessment was performed or explain how the observations were handled analytically.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Left Ventricular Mass Index, measured over Baseline.

Left ventricular mass index is the primary endpoint. It is a continuous measure of the mass of the left ventricle adjusted as an index and is reported in g/m2. The registry describes it as measured by 2D echocardiography at baseline. This endpoint represents cardiac structure rather than a clinical event such as heart failure or an arrhythmia.

In general, a structural measure can help characterize differences in the heart between groups, while a continuous measurement preserves more detail than reducing participants to categories. The mean is a way to describe the central value in a group, and the standard deviation describes variability among measured values. The registry identifies the primary outcome as a mean with standard deviation as the dispersion measure. However, the record does not report either group’s mean or standard deviation, nor a between-group estimate or uncertainty interval. The registry record therefore identifies what was intended to be measured but does not permit a conclusion about the observed contrast.

The comparison also has limits in interpretation. A difference in a baseline echocardiographic measure would describe an association between the exposure-defined groups in this study; it would not by itself establish that in-utero exposure caused the difference. The registry does not provide results showing whether left ventricular mass index differed, or whether any difference was clinically consequential.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

Left ventricular mass index is a continuous echocardiographic measure of cardiac structure. The registry specifies that it was measured by 2D echocardiography at baseline and expressed in g/m2. A continuous outcome can retain gradations in the measurement rather than classifying each child only as having or not having a condition. The planned summary is a mean, accompanied by a standard deviation. In general, the mean describes the center of a set of measurements, while the standard deviation describes how spread out individual measurements are around that center.

Those summaries answer different questions. A group mean describes its average observed measurement; the standard deviation describes variability among measurements. Neither alone is a direct measure of the precision of a comparison between groups. Precision of a group contrast is commonly conveyed with a confidence interval. In general, a confidence interval gives a range of values compatible with the data and the method’s assumptions. The registry record does not report means, standard deviations, a contrast, or a confidence interval for the primary endpoint.

What would a comparison estimate?

A comparison of group means would describe the difference in average left ventricular mass index between the exposure-defined groups. Because the study is not described as randomized and allocation is not stated, such a difference would be an observational association. Groups can differ in ways other than the exposure, and the registry record does not provide enough information to determine what factors were measured or adjusted for. The study objective mentions age- and gender-matched controls, but the record does not explain how matching was conducted or incorporated in analysis.

In general, adjustment can account statistically for measured characteristics included in a model, but it cannot guarantee that groups are comparable on unmeasured factors. The registry does not report an adjusted analysis plan or identify covariates used in any model. It also does not provide enough outcome information to assess an unadjusted comparison. A result from a nonrandomized comparison should not be interpreted as a causal effect solely because an analysis yields a difference or a small p-value.

How should uncertainty and significance be read?

A p-value, when reported, describes how incompatible the data are with a specified null model under its assumptions; it does not measure the size or clinical importance of a difference. A confidence interval is generally more informative about the range of effect sizes compatible with the data. The registry record does not report either statistic for the primary measure. No conclusion about statistical significance, precision, or the direction of a result can be made from the outcome information recorded there.

For continuous measures, distributional assumptions can matter. A mean and standard deviation are most straightforward to interpret when the measurement distribution is reasonably characterized by those summaries. If data are strongly skewed or contain influential values, other summaries or methods may be useful. This is a general statistical consideration, not a claim about this study’s data: the registry does not report distributions, diagnostic checks, or methods for handling outliers.

What are the secondary measures?

The registry lists global strain rate, systolic myocardial velocity during systole (S'), early-to-late diastolic filling ratio, and myocardial wall velocity during early diastole as secondary outcomes. These measures address additional aspects of cardiac function beyond the primary structural measure. The record identifies six outcome measures and six analyses, but provides no numerical results for these analyses. It does not specify the summary measure or statistical model for each secondary outcome, so those details are not reported in the registry record.

When measurements are continuous, a group comparison may be expressed using means and a difference in means, provided that summary is suitable for the data and analysis. Some measures may require different methods depending on their distribution and measurement properties. The registry does not give enough information to establish which method was used. The number of listed analyses alone does not reveal whether the analyses were prespecified, adjusted, exploratory, or based on the same analysis population.

What do the planning assumptions mean?

The record includes assumptions for a planning illustration based on the observed effect: a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The illustration considers effects defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study used those values for its design or analysis. The registry does not report the original sample-size justification or indicate that the illustration represents observed power. In general, sample-size calculations estimate how much information a future study would need under chosen assumptions; they do not establish the probability that a completed study’s finding is true.

The record does not report an inferential model, a prespecified significance threshold for the study’s actual analyses, or any recalculated estimate. There is therefore no basis in the registry record for comparing a sponsor analysis with an independent recalculation. Any interpretation should distinguish between an analysis plan, a planning illustration, and the results actually reported; only the outcome definitions and planning assumptions are available in this record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Healthy Control", "Exposed to HIV/HAART")
n   <- c(30, 30)
m   <- c(67, 60)
sp  <- c(12, 9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Healthy Control  30  67.000  12.000  62.519  71.481
CARM  Exposed to HIV/HAART  30  60.000  9.000  56.639  63.361

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies six outcome measures and six analyses, including the primary endpoint and listed secondary cardiac measures. It does not report how the analyses were organized, whether all were prespecified, or whether any were exploratory. A multiplicity strategy is not reported in the registry record. When several outcomes are tested, the chance of at least one apparently unusual result can increase if each is evaluated separately without accounting for the collection of tests. In general, investigators may address this by defining a primary outcome in advance, adjusting inferential thresholds, or treating secondary findings as exploratory. The record does not say which approach was used, so no adjustment or interpretation hierarchy should be assumed.

Missing-data methods are also not reported in the registry record. The listed enrollment is 60, but the record does not state how many participants had usable measurements for the primary endpoint or each secondary outcome. It does not describe exclusions after enrollment, reasons for missing echocardiograms, imputation, or sensitivity analyses. Therefore, the outcome-specific analysis populations and the possible effect of missing observations cannot be assessed.

The registry’s primary outcome population field is blank. No details are reported about the statistical analysis population, such as whether analyses included all enrolled participants or only those with complete measurements. The record also does not describe handling of protocol deviations or the analysis of any matched structure. These omissions limit assessment of reproducibility and of how well the analyses correspond to the stated objective.

12. Safety Results

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

Other (non-serious) adverse events

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

The registry lists zero serious adverse events and zero other adverse events for the Healthy Control group, with 30 participants at risk, and the same recorded counts with 30 participants at risk for the Exposed to HIV/HAART group. Deaths are not reported in the registry record; a blank or unreported death entry should not be interpreted as a recorded zero. The registry does not list serious adverse-event terms.

These entries are counts recorded in the registry, not a complete account of how safety events were defined, collected, reviewed, or followed over time. The record does not describe the observation period for adverse events, event ascertainment procedures, or whether all enrolled participants contributed to safety follow-up. Zero recorded events therefore means that the registry lists no events in these categories; it does not establish that no events occurred or that the groups had equivalent safety experience. The study is a comparison of exposure-defined cohorts, not a randomized treatment-safety trial.

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

The registry record establishes that the study was designed to characterize heart function in HIV-negative, pre-pubertal children exposed to HIV and HAART in utero and compare them with healthy controls. It identifies left ventricular mass index, measured by 2D echocardiography at baseline, as the primary outcome. It also gives the exposure and comparator descriptions and lists additional cardiac measures.

The registry record does not report the numerical findings for the primary or secondary outcomes. As a result, it does not show whether the groups differed in left ventricular mass index, how large any difference was, or how uncertain an estimate would be. It cannot support a claim that a difference was present, absent, statistically significant, or clinically important. A missing result should not be read as a null result.

The study’s nonrandomized comparison also limits causal interpretation. The record states that allocation is not specified and that the arms are not a like-for-like control comparison. Any observed contrast, if results were available, would need to be interpreted in light of possible differences between the groups and the analysis methods used. The registry does not report enough detail to assess adjustment or residual confounding.

The background rationale discusses possible later heart problems and asks whether earlier findings persist, worsen, or resolve before puberty. The primary outcome is listed at baseline, and the registry does not report longitudinal changes or future clinical events. The study record therefore does not establish what happens to heart function over time or whether the measured findings predict later outcomes. Its contribution in the registry is the documented research question and measurement plan; the outcome evidence needed to answer that question is not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a focused question about cardiac structure and function in HIV-negative children who experienced HIV and HAART exposure in utero. It distinguishes prenatal exposure from HIV infection in the child and uses a healthy control group as a comparison. That distinction is important for defining the population to which the research question applies. The registry also identifies an objective that is developmental: whether previously described heart-function concerns persist, worsen, or resolve before puberty.

Statistically, the study illustrates why an outcome definition is not the same as an outcome finding. The record specifies a continuous primary measure, its echocardiographic method, its units, and its baseline timeframe. Those details clarify what was intended to be measured. Without the reported group summaries and comparison estimates, however, readers cannot assess the magnitude, direction, or precision of an observed difference.

The design description matters as well. A nonrandomized, exposure-defined comparison can identify patterns between groups, but measured or unmeasured group differences may complicate causal interpretation. The registry’s statement that the arms are not a like-for-like control comparison is a specific caution against treating the contrast as if exposure were randomly assigned. Matching is mentioned in the objective, but its implementation is not described.

The listed secondary outcomes broaden the cardiac characterization, while the absence of reported multiplicity procedures, analysis populations, and missing-data methods limits evaluation of how findings would be interpreted across outcomes. The record therefore offers a useful account of the question and planned measurements but not enough reported results or methods to judge the evidential strength of an outcome conclusion.

15. 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 record constrain interpretation. The most immediate is that the primary and secondary outcome results are not reported in the registry record. Without group means, standard deviations, contrasts, or uncertainty measures, the observed cardiac measurements cannot be characterized. The completed status does not fill this reporting gap.

The comparison is not randomized, and allocation is not stated. The registry explicitly cautions that the arms are not a like-for-like control comparison. Although the study objective mentions age- and gender-matched controls, the registry does not describe matching procedures, whether matching was achieved, or how matching was reflected in analysis. Potential differences between the groups therefore cannot be evaluated from the record.

The primary outcome timeframe is baseline, while the background question concerns persistence, worsening, or resolution during pre-pubescence. The registry does not report repeated measurements or longitudinal analyses. It also does not report clinical outcomes such as later heart failure, arrhythmias, or heart attack as results of this study. The rationale should not be mistaken for evidence that these outcomes occurred.

Other details needed to assess the analysis are not reported in the registry record: eligibility and recruitment procedures, outcome-specific analysis populations, missing-data handling, covariate adjustment, the statistical model, and multiplicity control. The registry lists six outcome measures and six analyses but does not explain how they relate to a prespecified analysis plan. Safety-event ascertainment and deaths are also not fully described; deaths are not reported in the registry record. These gaps prevent assessment of completeness, analytic choices, and the robustness of any inferred comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Heart Function in HIV-Negative Children Exposed to HIV and HAART — NCT01107834.
• Registry record last updated 2016-07-20; status last verified 2016-06.
• Results first posted 2016-07-20.
• 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.

19. Record Summary

NCT01107834 is a completed study sponsored by Washington University School of Medicine, with enrollment listed as 60. The registry gives a start date of 2010-05 and a primary completion date of 2011-12. The study compares HIV-negative children exposed to HIV and HAART in utero with HIV-negative children born to healthy, HIV-negative women. Its primary outcome is baseline left ventricular mass index measured by 2D echocardiography and expressed in g/m2.

The registry also lists secondary cardiac measures and identifies six outcome measures and six analyses. It describes the comparison as nonrandomized, with allocation not stated, and cautions that the arms are not a like-for-like control comparison. Numerical results, detailed analysis methods, missing-data procedures, and multiplicity methods are not reported in the registry record. The safety entries list zero serious and zero other events in each group; deaths are not reported in the registry record.