HIV And Parasitic Infection (HAPI) Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HIV And Parasitic Infection (HAPI) Study (NCT05323396), a non-randomized na study. The primary outcome is Mean Soluble CD14 (sCD14) Levels.

2. Clinical Question

The registry describes a study of intestinal parasitic infection, intestinal damage, and immune activation among people living with HIV. Its primary endpoint is a comparison between groups defined by parasite test results, rather than a randomized comparison of treatment against no treatment. The primary comparison therefore asks whether baseline mean sCD14 levels differ by parasite status; it does not by itself estimate the effect of antiparasitic medication.

The study description also outlines questions about the prevalence of intestinal parasitic infections and about biomarkers before and after treatment in parasite-positive participants. It identifies sCD14, sCD163, and intestinal fatty acid binding protein (I-FABP) as biomarkers of interest. These are stated aims and hypotheses, not reported findings. Numerical results for the primary comparison and for the other aims are not reported in the registry record.

3. Trial Design

The HIV And Parasitic Infection (HAPI) Study is listed as completed, with enrollment of 120. Its recorded start date is 2022-05-02 and its primary completion date is 2023-08-04. The registry lists the phase as NA. The design is parallel and non-randomized, with no masking.

Participants were evaluated for intestinal parasitic infection by stool microscopy or stool PCR. The arm descriptions state that participants positive by either method were treated for the detected infection and entered the parasite-positive arm. Participants negative by all tests on the initial sample collection were assigned to the parasite-negative, no-intervention arm. The record names antiparasitic medication as the intervention.

Because group assignment followed parasite-test status rather than random allocation, the groups are not like-for-like randomized controls. Differences in their measured outcomes could reflect parasite status, other differences between participants, or both. The listed primary analysis compares the groups at baseline, so it is an association between group membership and baseline sCD14 rather than a randomized estimate of treatment effect.

The study description gives a broader purpose: investigating whether parasitic infections relate to intestinal damage and immune activation among people living with HIV, and whether biomarker levels change after treatment of co-infection. It also states a hypothesis that highly sensitive stool PCR testing would identify a greater parasite burden than historically reported using stool microscopy. These are research questions and hypotheses, not evidence that the expected patterns occurred. Detailed eligibility criteria, recruitment procedures, follow-up schedule, and participant flow 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.

Before assignment: After signing informed consent, participants provide laboratory samples for evaluation of parasitic infection.

Overall Study

Reasons for not completing this 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.

6. Primary Endpoint

The registry lists the primary outcome as Mean Soluble CD14 (sCD14) Levels, measured over Baseline.

The primary endpoint is mean soluble CD14 (sCD14) level in plasma at baseline, reported in µg/mL. The registry states that levels are measured in all patients at the baseline visit and that the mean in the parasite-positive group is compared with the mean in the parasite-negative group using Student's unpaired t-test. The stated dispersion measure is the standard deviation.

sCD14 is one of the biomarkers identified in the study description as reflecting immune activation. The broader biomarker aims also include sCD163 and intestinal fatty acid binding protein (I-FABP), described as reflecting immune activation and intestinal damage. As a biomarker endpoint, sCD14 captures a laboratory measurement; it is not itself a direct measure of morbidity, mortality, or a patient-experienced clinical outcome.

In general, a comparison of group means describes whether the average measured level differs between the groups. The standard deviation describes variability among individual measurements within a group. Interpretation depends on the estimated difference and its uncertainty, as well as on the comparability of the groups and the quality and completeness of the measurements. The numerical group means, standard deviations, group sizes for this endpoint, and inferential results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a measured plasma concentration summarized as a mean. The registry specifies Student's unpaired t-test to compare the mean baseline sCD14 level in the parasite-positive group with the mean in the parasite-negative group. An unpaired test is used for two groups made up of different participants, rather than paired measurements from the same individuals. The endpoint description specifies the standard deviation as the measure of dispersion.

What does a comparison of means address?

In general, a group mean gives the arithmetic average of the recorded measurements in that group. A difference between group means describes the observed separation in average values. It does not show how much individuals overlap, and it does not alone explain why the groups differ. Standard deviations help describe within-group spread, while the estimated difference and its uncertainty address how precisely the group contrast has been estimated.

Student's unpaired t-test evaluates the data against a null model in which the group means are equal. In general, the conventional Student version uses a common variance assumption for the two groups and relies on independent observations. The registry names the test but does not report checks of its assumptions, any alternative method, or details about how distributions and outliers were handled. Those procedures are not reported in the registry record.

How should uncertainty be read?

In general, a confidence interval conveys uncertainty around an estimated contrast, while a p-value summarizes how unusual the data would be under the test's null model. Neither quantity communicates the biological importance of a result on its own. Estimates, intervals, and p-values for the primary comparison are not reported in the registry record, so neither the strength of evidence nor the precision of an observed contrast can be assessed from this record.

Non-randomized groups require particular care in interpretation. Here, parasite test status defines the comparison groups, and the arm descriptions link positive status to antiparasitic treatment. General statistical reasoning indicates that group differences can reflect factors other than the exposure or status of interest. The registry record does not report an adjusted primary analysis or a set of covariates used to address potential confounding. The primary description instead identifies a comparison of group means using an unpaired t-test.

What do the planning assumptions mean?

The registry describes planning illustrations based on a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. In general, such calculations illustrate how a hypothetical design's required number of participants per arm depends on assumptions about the effect size and variability. They are not observed trial outcomes and do not show the probability that this completed study detected an effect. The registry record does not report its own design justification or actual power calculation. Sample-size illustrations are planning exercises, not observed power.

The assumptions also matter because the primary comparison is not randomized. Equal allocation is a calculation assumption, not evidence that the observed groups had equal sizes. Likewise, a calculation based on an observed effect is conditional on that effect estimate and its context; it does not remove bias or uncertainty in the underlying comparison. No numerical planning illustration is stated in the registry record.

General statistical context: over-dispersion occurs when data vary more than a chosen model expects. When that happens, a model's standard errors can be too small if the extra variability is ignored, making intervals too narrow and p-values too optimistic. The registry identifies a continuous endpoint and a t-test, but does not report an over-dispersion assessment or evidence that over-dispersion was a concern. This general issue should not be mistaken for a reported feature of this study.

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("Parasite-positive Arm", "Parasite-negative Arm")
n   <- c(36, 84)
m   <- c(1.42, 1.52)
sp  <- c(0.39, 0.42)
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  Parasite-positive Arm  36  1.420  0.390  1.288  1.552
CARM  Parasite-negative Arm  84  1.520  0.420  1.429  1.611

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and six analyses. This indicates that the study record contains multiple outcomes or analyses, but it does not specify how the analyses relate to one another, which outcomes were designated secondary, or whether any multiplicity procedure was used. A correction for multiple testing, a testing hierarchy, and a prespecified family of hypotheses are not reported in the registry record.

In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase. Researchers may address this by defining a primary outcome in advance, adjusting significance thresholds, or interpreting secondary analyses as exploratory. The registry identifies mean baseline sCD14 as the primary endpoint, but does not report the broader statistical plan or a multiplicity strategy. Any interpretation of additional analyses therefore requires caution, and their numerical results are not reported in the registry record.

Methods for missing data are not reported in the registry record. The record does not describe the amount or pattern of missingness, whether participants with incomplete measurements were excluded, or whether imputation or another method was used. Analysis populations, including any distinctions between enrolled, treated, and analyzed participants, are not reported in the registry record. Enrollment of 120 does not establish the number contributing to the primary endpoint.

In general, missingness can affect both the size and the interpretation of an estimate, depending on why data are missing and how the analysis handles them. Without participant flow and missing-data details, the completeness and representativeness of endpoint data cannot be evaluated from the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry reports zero serious adverse events among 36 participants listed as at risk in the parasite-positive arm. It also reports zero other adverse events among 36 participants listed as at risk in that arm, and zero deaths. These are the recorded counts; the registry does not provide further event descriptions in the information.

For the parasite-negative arm, the registry lists zero participants at risk for serious or other adverse events, zero affected participants, and zero deaths. A zero at-risk count means there is no listed denominator for interpreting the arm's zero affected count as evidence that no events occurred among participants. The figures therefore do not support a like-for-like safety comparison between the arms.

In general, adverse-event counts should be read alongside the number of participants monitored, the observation period, and the definitions and collection procedures used. The registry record does not report detailed safety ascertainment methods or exposure time. The listed counts describe what was recorded; they cannot establish that an intervention is free of risk.

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

The record describes a completed, non-randomized study of intestinal parasitic infection and biomarkers among people living with HIV in Lilongwe, Malawi. Its primary endpoint is a comparison of baseline mean sCD14 between parasite-positive and parasite-negative groups. The registry reports the test specified for that comparison, but numerical endpoint results are not reported in the registry record. There is therefore no basis in this record to state whether the groups differed, in which direction, or with what precision.

The study's aims include assessing parasite prevalence and examining biomarkers related to intestinal damage and immune activation. Its description also proposes assessing biomarkers before and after treatment in parasite-positive participants. Those questions may be important for understanding the relationship between parasite status and biomarkers, but stated aims and hypotheses are not findings. Numerical results for these questions are not reported in the registry record.

The non-randomized design also limits causal interpretation. Parasite-positive and parasite-negative participants were defined by test results, not randomly assigned to infection status or treatment. A baseline association would not establish that parasitic infection caused a biomarker difference. Nor would it establish that antiparasitic medication changed a biomarker or improved morbidity or mortality. The registry description's broader goal concerning morbidity and mortality is a rationale, not a reported clinical outcome.

In general, clinical meaning depends on the size and precision of an effect, how it relates to patient outcomes, and whether the design supports the proposed interpretation. The registry record does not report the primary estimate, confidence interval, or p-value, and does not report evidence about clinical outcomes such as morbidity or mortality. The available information supports describing the research question and design, not drawing conclusions about treatment benefit or lack of benefit.

14. Why This Trial Matters Statistically

This study illustrates a common statistical distinction: comparing groups defined by an observed characteristic is not the same as comparing randomly assigned treatments. Here, intestinal parasite test status determined the study arms, and the positive arm received antiparasitic medication. That structure can address whether biomarker levels are associated with parasite status, but it does not by itself isolate a treatment effect.

The primary endpoint is a continuous biomarker, mean baseline sCD14. Reporting the mean together with dispersion and an uncertainty interval would help readers assess both the estimated group contrast and its precision. The registry identifies the test and dispersion measure, but numerical results are not reported in the registry record. This makes clear how the analysis was intended to be framed while leaving its empirical result unavailable in the record.

The study description also distinguishes between a biomarker question and a broader clinical motivation concerning morbidity and mortality. Biomarkers can help characterize biological processes, but a biomarker comparison does not automatically establish a change in clinical outcomes. Keeping those questions separate is important when interpreting the stated aims.

Finally, the record lists multiple outcomes and analyses, while details about multiplicity, missing data, and analysis populations are not reported. Those omissions matter for judging how complete and selective the reported evidence may be. The registry's planning assumptions are also separate from observed evidence: a planning illustration cannot establish that a study had adequate power or that a result was detected. These distinctions are useful when reading clinical research records in which design details are available but numerical outcome results are not.

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.

The primary limitation for interpretation is that numerical results for the listed primary endpoint are not reported in the registry record. Group means, standard deviations, the estimated contrast, confidence interval, and p-value are absent, preventing assessment of the direction, magnitude, or precision of the comparison.

The non-randomized design means the parasite-positive and parasite-negative groups may differ in ways beyond parasite status. The registry record does not report an adjusted primary analysis or the covariates considered, so potential confounding cannot be evaluated. The treatment received by the parasite-positive group also means that the study arms are not a randomized treatment-versus-control comparison.

The record describes evaluation using stool microscopy or stool PCR, but detailed test procedures, timing beyond the initial sample reference, and how discordant test results were handled are not reported in the registry record. The participant flow and the number contributing data to each endpoint are also not reported. Recorded enrollment alone does not establish the analysis sample size.

Other details needed to assess robustness are not reported in the registry record, including missing-data handling, analysis populations, multiplicity procedures, and checks of the primary test's assumptions. The study description includes several biomarker aims, but numerical results for those outcomes are not reported. Finally, the safety information lists no at-risk participants in the parasite-negative arm, so it does not permit a meaningful between-arm safety comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HIV And Parasitic Infection (HAPI) Study — NCT05323396.
• Registry record last updated 2025-07-16; status last verified 2025-04.
• Results first posted 2024-07-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The HAPI Study is listed as completed, with enrollment of 120, a recorded start date of 2022-05-02, and a primary completion date of 2023-08-04. It is a non-randomized, unmasked, parallel study listed as phase NA.

Participants were grouped by intestinal parasite test status. The parasite-positive group was treated with antiparasitic medication; the parasite-negative group received no intervention. The primary endpoint is mean baseline plasma sCD14, compared between groups using Student's unpaired t-test.

The registry record does not report numerical results for the primary endpoint. It also does not report the detailed statistical plan, missing-data methods, or analysis populations. Safety counts include zero serious adverse events among 36 at risk in the positive arm; the negative arm has zero participants listed at risk.