Improving Prognosis in HIV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Improving Prognosis in HIV Infection (NCT02640625), a na phase 1, phase 2 study. The primary outcome is Adverse Effects.

2. Clinical Question

3. Trial Design

NCT02640625, titled “Improving Prognosis in HIV Infection,” is recorded as a completed phase 1 and phase 2 study sponsored by Oslo University Hospital. The official title describes adjuvant mucosal therapy in HIV-infected men with insufficient response to antiretroviral therapy. The registry lists a single-group model, allocation as not applicable, and no masking. Enrollment is recorded as 20. The study start is listed as 2016-01 and primary completion as 2017-03.

The intervention is a probiotic compound listed as a dietary supplement. Its stated components are Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium animalis subsp. lactis, and Streptococcus thermophilus. The primary objective is safety in cART-treated INR patients with chronic HIV infection. Secondary objectives include exploring biological effects of probiotics and investigating differences between cART-treated HIV-infected INR and non-INR patients in gut microbial composition and mucosal barrier function.

This design is not a randomized comparison of the probiotic with a control treatment. The registry explicitly notes that the listed arms are not a like-for-like control comparison. As a result, the posted primary count describes participants in the probiotic intervention group; it does not estimate a comparative treatment effect against a concurrent control group. The registry record does not report a detailed protocol, eligibility criteria, probiotic dose, administration schedule, or procedures for assigning participants to any comparison group.

The record names secondary outcomes involving gut microbiota composition, epithelial gene expression, lamina propria T-cell subsets, systemic T-cell intracellular signaling, and systemic markers of immune activation. It reports 8 outcome measures, but the number alone does not describe which measures have posted results or how they were analyzed.

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

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 Adverse Effects, measured over 10 weeks.

The primary endpoint is “Adverse Effects,” described as the number of participants who experienced adverse effects. It is a participant count over a 10-week timeframe. The posted result identifies 0 participants with serious adverse effects and 1 participant with other adverse effects in the probiotic intervention group. These are category-specific counts, not a comparative estimate against a control group.

Safety endpoints are used to record unwanted health events during an intervention study. A participant count answers how many participants met the recorded outcome definition; it does not, by itself, describe the nature, severity, timing, or cause of an event. Those details and the operational definition of an adverse effect are not reported in the registry record. The record also does not state how events were elicited, assessed, or attributed to the probiotic.

In general, a count is a direct way to present the number of people meeting a specified outcome definition. It is distinct from an event rate, which accounts for time at risk, and from a risk comparison, which contrasts groups. The registry endpoint is a count, and no time-adjusted rate or control-group contrast is reported. The 10-week timeframe defines the period associated with the posted endpoint; it does not establish whether follow-up was complete for every participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count measure?

The primary outcome is a count of participants who experienced adverse effects, grouped into serious and other adverse-effect categories. This kind of endpoint records whether a participant meets the outcome definition during the specified observation period. It is not a count of all separate events: a participant-level measure and an event-level measure answer different questions. The registry describes the endpoint as the number of participants, so the posted figures should be read at the participant level.

In general, participant counts are easy to interpret when the outcome definition and observation period are clear. Their interpretation depends on consistent event identification and complete follow-up. The registry record gives a 10-week timeframe but does not report the event definition, ascertainment procedure, or completeness of follow-up. Those omissions limit assessment of how consistently events could have been identified across participants.

What would a comparison add?

In general, a controlled comparison helps distinguish outcomes that occur during treatment from outcomes that might have occurred in the absence of that treatment. A randomized, like-for-like comparison can support a causal interpretation when its design and conduct are appropriate. This study is recorded as single-group, with allocation not applicable; the registry warns that the arms are not a like-for-like control comparison. Thus, the primary adverse-effect counts describe the intervention group but do not estimate a difference between treatment and control.

The registry also describes an objective to investigate differences between cART-treated INR and non-INR patients for gut microbial composition and mucosal barrier function. That objective does not make the primary safety result a randomized treatment comparison. The registry record does not report the group definitions, assignment process, or a safety contrast for those patients.

How should uncertainty be understood?

In general, an estimate based on observed participants is subject to sampling variability: another study of a similar population could produce a different count or estimate. A confidence interval is a statistical range designed to express uncertainty around an estimate under stated assumptions. A hypothesis test evaluates data against a specified null hypothesis and statistical model. Neither an interval nor a test result for the primary safety count is reported in the registry record. Therefore, the posted counts do not quantify statistical uncertainty or establish a difference from any benchmark.

The posted planning assumptions describe a planning illustration, not the trial’s own design: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation are specified, with the target effect expressed as a fraction of the observed effect. The record does not report numerical planning outputs in the registry record for this analysis. More importantly, such planning values are not observed power and should not be read as evidence about the precision or strength of the completed study’s result. The single-group study record is not itself a two-arm randomized comparison.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability in count data exceeds what a statistical model assumes. If a model assumes that counts vary in a particular way but the data vary more, standard errors and uncertainty intervals can be too small unless the analysis accounts for the extra variability. This concept is relevant to some count outcomes, especially when modeling repeated or clustered events. The posted primary endpoint is a participant count, and the registry does not report a count model, an over-dispersion assessment, or an adjustment for it. No claim about over-dispersion in this study can be made from the posted count alone.

What does the absence of analysis details mean?

The registry reports 0 analyses. That is a description of what is recorded in the registry, not proof that no analyses were conducted. The analysis method, handling of missing outcomes, definition of analysis populations, and any adjustments are not reported in the registry record. Without those details, readers cannot determine whether the counts reflect all enrolled participants, a prespecified subset, or a particular missing-data approach. The result can still be described as posted, but its analytic provenance cannot be fully assessed from the record.

For this endpoint, the most transparent reading is descriptive: the registry lists the number of participants with serious and other adverse effects and the corresponding at-risk counts. Further claims would require methods and outcome details not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Probiotic Intervention")
n      <- c(20)
events <- c(1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Probiotic Intervention  20  1  5.0  0.1  24.9  0.9  23.6  1.2  23.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies 8 outcome measures and names secondary objectives related to gut microbiota, epithelial gene expression, lamina propria T-cell subsets, systemic T-cell intracellular signaling, and systemic markers of immune activation. The record reports 0 analyses. These entries do not establish how many outcomes were tested, whether any were analyzed together, or whether results were selected for posting.

When a study examines several outcomes or performs several statistical tests, the chance of finding at least one apparently unusual result can increase. In general, a prespecified analysis plan can clarify which outcomes are primary, how secondary outcomes will be treated, and whether any adjustment for multiple comparisons is planned. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or an analysis plan. It is therefore not possible to assess whether statistical claims across outcomes account for multiple testing.

Missing-data handling and analysis populations are also not reported in the registry record. The record does not describe the amount or pattern of missing outcome data, reasons for missingness, imputation, or whether the posted count includes every enrolled participant. Enrollment is listed as 20, and the adverse-effect categories each list 20 at risk; those entries alone do not disclose follow-up completeness or the handling of any unavailable information.

In general, missing data can affect both the estimate and its uncertainty, depending on why information is missing and how the analysis handles it. An analysis population can also matter: an intention-to-treat, per-protocol, or safety population may include participants according to different rules. None of those populations or rules is reported. These omissions do not invalidate the posted counts, but they restrict the assessment of how the counts were derived and how broadly they represent the enrolled study population.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-effect result is 0 participants affected among 20 at risk in the probiotic intervention group. The other adverse-effect category lists 1 participant affected among 20 at risk. These are the registry’s participant-level counts for the 10-week primary endpoint timeframe. No serious adverse event terms are listed.

The serious and other categories should not be combined into a new total, and the counts should not be interpreted as a comparison between treatments. The record does not identify the specific other adverse effect, explain its severity, give its timing, or state whether investigators considered it related to the probiotic. It also does not report event ascertainment procedures or whether participants were followed for effects after the 10-week timeframe.

In general, a zero count in a study group means that no participant was recorded with the specified outcome under the study’s reporting process. It is not proof that the outcome is impossible or that the true risk is zero. A nonzero count likewise does not establish that an intervention caused the event. The single-group design and the absence of event details limit causal and comparative interpretation.

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

The result means that the registry records 0 participants with serious adverse effects and 1 participant with other adverse effects in the probiotic intervention group during the 10-week endpoint timeframe. It provides a descriptive account of the reported safety outcome for this study. The at-risk count shown for each category is 20.

It does not establish that the probiotic is safe in general, or that serious adverse effects cannot occur. A study’s observed counts describe what was recorded in the study; they do not alone provide a precise estimate of the range of possible outcomes in other settings or populations. The registry record does not report a confidence interval or other uncertainty estimate for the safety outcome.

It also does not establish that the probiotic caused the other adverse effect or that the intervention changed the risk of adverse effects. The single-group design has no like-for-like control comparison for this endpoint, so outcomes under the intervention cannot be contrasted with outcomes under a concurrent control condition. The registry specifically cautions that the arms are not a suitable like-for-like comparison.

The primary result does not answer whether probiotics altered gut microbiota, epithelial gene expression, mucosal T-cell subsets, systemic T-cell signaling, or systemic immune activation markers. These are listed as secondary outcomes, but the adverse-effect count is not evidence about those biological outcomes. Nor does the result establish a benefit for HIV infection or immune response. The study’s stated primary objective is safety, and the posted primary outcome concerns adverse effects.

In general, statistical interpretation should match the design, endpoint, and available results. A descriptive count supports a statement about the participants and period recorded; it does not support a treatment-effect claim without an appropriate comparison and analysis. Any broader conclusion would require information about outcome definitions, follow-up, analysis methods, and relevant comparison data that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why the design determines the scope of a result. A participant count can communicate how many people met a safety outcome in a study group, but a single-group count cannot by itself estimate what would have happened under a control condition. The distinction between describing an outcome and estimating a treatment effect is central to interpreting clinical evidence.

The primary endpoint is also a useful reminder that outcome labels need operational detail. “Adverse Effects” is a broad label, while the posted result distinguishes serious from other effects. Without descriptions of the events, criteria for seriousness, ascertainment procedures, and attribution, readers can understand the counts but cannot fully evaluate how those classifications were made.

The record lists exploratory biological objectives alongside a primary safety objective. Such a range of outcomes can generate different kinds of evidence, and each requires an appropriate analysis and clear reporting. The registry reports 8 outcome measures but 0 analyses. That makes it especially important not to treat listed objectives as though they were reported findings or to infer a statistical conclusion from an outcome count.

Finally, the registry’s note that the arms are not a like-for-like control comparison prevents a common interpretive error: treating every group label as a valid comparative design. Statistical conclusions depend not only on the numbers, but also on who was compared, how participants entered each group, how outcomes were measured, and how uncertainty was handled. Those design and analysis details are not all reported in the registry record, so the strongest defensible reading remains descriptive and limited to the posted counts.

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 interpreting the safety result is the single-group design. No like-for-like control comparison is listed, and the registry explicitly cautions against treating the arms as a control comparison. The result therefore cannot estimate a comparative safety effect or separate effects associated with the intervention from events that might occur in the absence of it.

The endpoint is described as the number of participants experiencing adverse effects, but the registry record does not report the operational definition of an adverse effect, event-assessment procedures, or criteria used to distinguish serious from other effects. The specific other adverse effect is not reported in the registry record. The record also does not state whether events were judged related to the probiotic.

Details needed to evaluate follow-up are not reported in the registry record. Although the primary endpoint timeframe is 10 weeks and the adverse-effect categories each list 20 at risk, the record does not describe completeness of follow-up, missing observations, or procedures for handling missing data. The analysis population and statistical methods are likewise not reported.

The study’s stated population is specific: men with chronic HIV infection receiving cART who have an insufficient immunologic response. The record does not report further eligibility criteria or enough information to assess how closely participants represent other populations. The probiotic dose and administration schedule are also not reported in the registry record.

Finally, the registry lists secondary biological outcomes but reports 0 analyses. The availability and findings of those outcomes cannot be inferred from their listing. The posted safety counts should therefore be interpreted narrowly, without extending them to biological effects, comparative safety, or treatment efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Improving Prognosis in HIV Infection — NCT02640625.
• Registry record last updated 2021-12-06; status last verified 2021-12.
• Results first posted 2020-03-27.
• 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

NCT02640625 is a completed phase 1 and phase 2, single-group study sponsored by Oslo University Hospital. The registry lists enrollment of 20, no masking, allocation as not applicable, a study start of 2016-01, and primary completion of 2017-03. The study concerns probiotic therapy in cART-treated men with chronic HIV infection and an insufficient immunologic response.

The primary endpoint is the number of participants experiencing adverse effects over 10 weeks. In the probiotic intervention group, the record lists 0 participants with serious adverse effects and 1 participant with other adverse effects; each category lists 20 at risk. The registry lists 8 outcome measures and 0 analyses.

The result is descriptive. The registry does not report a like-for-like control comparison, detailed event descriptions, a statistical analysis plan, missing-data procedures, or analysis populations. The posted safety count does not establish causation, comparative risk, efficacy, or the absence of effects beyond those recorded.