The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection (NCT00641641), a na na study. The primary outcome is Mean Change From Baseline Plasma HIV RNA (Log Copies/mL).

2. Clinical Question

3. Trial Design

The registry record describes an open-label, single-group study with no masking. Allocation is listed as NA, and the record explicitly identifies the study as not being a randomized comparison. It enrolled 16 participants. The study status is completed; the recorded start was 2008-03 and primary completion was 2011-03.

The intervention was tenofovir plus emtricitabine as a fixed-dose combination, administered orally once per day, and raltegravir administered orally twice per day. The study description says it examined the characteristics of HIV decay following introduction of this combination during primary and chronic HIV infection. It also describes interest in viral levels in different body and immune-system compartments, but the listed primary outcome is plasma HIV RNA.

With a single group, the primary outcome describes change over time among participants receiving the intervention. It does not compare that change with an untreated group or a group receiving another regimen. Open-label means masking was absent; the registry record does not report further details about how outcome assessments were conducted or whether laboratory measurements were masked.

The record does not report the protocol’s rationale for enrollment, the eligibility criteria, how primary and chronic infection were defined, or how many participants belonged to each group. It also does not report a detailed schedule beyond the primary outcome’s 12 assessments within 48 weeks. The registry record does not report the study’s statistical analysis plan, interim analyses, or a rationale for the chosen enrollment.

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: A screening period of less than 42 days prior to commencement of study drugs was employed

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intention to treat

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 Change From Baseline Plasma HIV RNA (Log Copies/mL), measured over 12 times within 48 weeks..

The primary endpoint is mean change from baseline in plasma HIV RNA, expressed in log copies/mL plasma. HIV RNA is a measure of viral material in plasma. A change from baseline describes how the measured level differs over follow-up from the participant’s starting value; the registry record defines the endpoint as the mean of 12 assessments minus baseline. The stated timeframe is 12 times within 48 weeks.

Using a mean across repeated assessments can describe the average trajectory over the specified follow-up measurements rather than relying on a single post-baseline measurement. The logarithmic scale expresses viral quantity on a transformed scale; in general, log transformation can make a highly skewed measurement easier to summarize and model. That is a general statistical rationale, not a description of an analysis method confirmed by the registry record.

The endpoint is listed as a continuous measure, with the mean as its summary parameter and standard deviation as its dispersion measure. These choices indicate the intended form of reporting, but the record does not provide the observed mean change, standard deviation, confidence interval, or analysis estimate. Therefore the numerical size and precision of the primary result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous and is defined as a mean change from baseline. In general, a continuous outcome can take a range of values, and its mean describes the arithmetic center of the observed measurements. The standard deviation describes dispersion of individual measurements around that mean. These are the summary parameter and dispersion measure identified for the endpoint. The numerical mean and standard deviation are not reported in the registry record.

What does change from baseline represent?

Change from baseline compares a follow-up measure with a starting measure. In this study, the registry record specifies that the change was calculated as the mean of 12 assessments minus the baseline value. This definition makes the repeated follow-up measurements part of the endpoint itself. It is not enough to know the definition to recover the result: the actual assessment values, or a reported summary, are needed, and those values are not reported in the registry record.

In general, change scores may be useful when the research question concerns movement from an individual’s starting level. Their interpretation depends on how baseline and follow-up are measured, how repeated assessments are combined, and how missing assessments are handled. Those implementation details, beyond the stated mean of 12 assessments minus baseline, are not reported in the registry record.

Why is dispersion important?

A mean alone does not show how similar or different participants’ outcomes were. Standard deviation gives a description of spread in the measured values. In general, a standard deviation is not the same as a standard error: the former describes variability among observations, while the latter describes uncertainty in an estimated mean. A confidence interval uses an estimate and its uncertainty to express a range of values compatible with the data and the analysis assumptions. The registry record does not provide a standard deviation, standard error, or confidence interval for the primary outcome.

What does a single-group analysis allow?

For a single group, a before-and-after summary can describe the observed course in that group. It does not provide the randomized contrast that would arise from comparing participants assigned to different groups. General causal interpretation is more limited when no concurrent comparison group is present, because observed change may reflect influences other than the intervention. The record lists allocation as NA and identifies the study as not a randomized comparison. It does not report a separate control arm or a between-group analysis.

The record also describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not a description of the actual single-group design. Such illustrations are hypothetical sample-size calculations: they explore how a study might be sized under stated assumptions about an effect and design. They are not observed power and do not add evidence about the outcome of this study. Numerical planning results are not reported in the registry record.

In general, a normal approximation uses properties of the normal distribution to estimate sampling behavior. Whether it is suitable depends on the data and analysis setting. The registry record does not report the detailed calculation method, variance assumptions, or the effect size used in the planning illustrations.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation exceeds what a statistical model assumes. If a model understates variation, standard errors may be too small and intervals may appear more precise than warranted. This concept is relevant to some models for counts or clustered data, but the listed primary endpoint is a continuous mean change. The registry record does not identify an over-dispersion model or report a model-based analysis, so over-dispersion cannot be assessed as a feature of the posted primary analysis.

The registry record reports 0 analyses for the listed outcome. It does not describe an inferential test, a model, adjustment for covariates, or a prespecified statistical analysis plan. No p-value or sponsor analysis estimate is reported in the registry record. General statistical explanations do not fill that gap: without the analysis details and outcome results, the numerical inferential findings cannot be reconstructed.

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("Drug Intervention")
n   <- c(16)
m   <- c(5.4)
sp  <- c(0.6)
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  Drug Intervention  16  5.400  0.600  5.080  5.720

11. Multiplicity, Missing Data and Analysis Populations

The primary outcome is identified as mean change from baseline in plasma HIV RNA, calculated using 12 assessments within 48 weeks. Although the registry record lists one outcome measure, it does not report whether there were additional planned endpoints, subgroup analyses, repeated statistical tests, or multiple comparisons. A multiplicity strategy, such as a procedure to control error rates across multiple tests, is not reported in the registry record.

The registry record describes the primary population as intention to treat. That label generally refers to analyzing participants according to a defined trial population rather than limiting analysis only to those who complete treatment, but the exact definition and implementation depend on the protocol. The record does not report which participants were included in the analysis, whether any participants were excluded, or how participants with missing outcome values were handled.

There is no reported account of withdrawals, missed assessments, imputation, or sensitivity analyses for missing data. This matters because the endpoint uses repeated measurements, and the availability of those measurements affects which participants can contribute to the mean. The enrollment of 16 does not indicate the number with complete outcome data or the denominator at each assessment.

The record lists 0 analyses for the primary outcome. It therefore does not provide enough information to assess whether the analysis followed a prespecified plan, how multiplicity was handled, or how missing data influenced the result. These analysis details are not reported in the registry record.

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 5% reporting threshold.

The safety entries list 0 serious adverse events among 16 participants at risk and 0 other adverse events among 16 participants at risk. These are the recorded counts for the intervention group. They describe the entries in the registry record; they do not establish that an event could not occur or that no event was missed.

The death count is not reported in the registry record. The record also contains no listed serious adverse-event terms. The absence of listed terms should be read alongside the zero serious-event count, not as additional detail about event monitoring or classification.

Safety counts are most informative when the observation period, event definitions, collection procedures, and participant follow-up are clear. Those details are not reported in the registry record. There is no comparison group, so the counts do not provide a comparative estimate of safety. They should be read as recorded counts in this single-group study, not as proof about the presence or absence of risk.

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

The registry record establishes that the study examined HIV decay after introduction of a combination of tenofovir, emtricitabine, and raltegravir in primary and chronic HIV infection. It describes a continuous primary endpoint based on plasma HIV RNA change from baseline and specifies repeated assessments within 48 weeks. It also records enrollment of 16 and the intervention-group safety counts.

However, the numerical primary outcome result is not reported in the registry record. Without that estimate and its variability or uncertainty, the magnitude and precision of the average change cannot be evaluated. The record does not report an inferential test or confidence interval, so it cannot support a conclusion about statistical uncertainty for the primary endpoint.

The single-group, open-label design also limits what a within-group change can establish. It does not supply a randomized comparison against another regimen or a control group. In general, change observed after treatment begins is not automatically attributable solely to treatment; a comparative design can help separate treatment effects from other influences. This record does not provide such a comparison.

The safety entries record 0 serious adverse events and 0 other adverse events among 16 participants at risk, while the death count is not reported in the registry record. These entries do not replace information about follow-up duration, event collection, or comparative safety.

Overall, the registry record describes the study question, treatment, design, endpoint, and recorded safety counts, but it does not report the primary outcome estimate or enough analysis detail to quantify the study’s finding. That distinction separates what the study set out to measure from what can be concluded from the posted results.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between an endpoint definition and a numerical result. The registry record describes a continuous outcome, the baseline reference, the repeated-assessment summary, the timeframe, and the intended population. Those details explain what the study aimed to quantify, but without the estimate and a measure of uncertainty they do not show the magnitude or precision of the observed outcome.

The design also matters for interpretation. This was an open-label, single-group study, and the registry record identifies it as not a randomized comparison. A within-group outcome can describe participants’ course over time, but it does not provide a randomized contrast. This is a useful reminder that statistical summaries cannot compensate for a design that lacks a concurrent comparator when the question concerns comparative effects.

The stated outcome uses repeated assessments to form a mean change from baseline. In general, repeated measurements can characterize outcomes across follow-up, while also raising questions about incomplete observations and analysis choices. The registry record does not report the missing-data approach or the analysis details needed to evaluate those choices.

Finally, the safety counts demonstrate why denominators and context matter. The record gives the number at risk and recorded event counts, but does not report the observation details needed to interpret how completely events were captured or compare safety across treatments. The statistical value of this record lies in clarifying the study’s structure and the limits of the available reporting, rather than in a numerical treatment-effect 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 trial-specific limitations follow directly from the registry record. The study is single group, open label, and not a randomized comparison. It therefore does not provide a concurrent control group for interpreting change over time. The record does not describe a comparator regimen or a comparative analysis.

The primary outcome is defined, but its numerical result is not reported in the registry record. The record also does not report the standard deviation, confidence interval, p-value, or model estimate for that outcome. As a result, neither the size of the average change nor its statistical precision can be assessed from the posted results.

The enrollment was 16, but the record does not report the number contributing data at each assessment, the number completing follow-up, or the handling of missing measurements. This is particularly relevant to an endpoint based on 12 assessments. Although the population is labelled intention to treat, the record does not state the operational definition or analysis population details.

The record does not report eligibility criteria, the numbers with primary versus chronic infection, the detailed statistical analysis plan, multiplicity procedures, interim analyses, or sample-size justification. The safety entries do not include the death count or details of observation and event collection. These omissions limit both reproducibility and interpretation of the endpoint and safety findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effect of Raltegravir on HIV Decay During Primary and Chronic Infection — NCT00641641.
• Registry record last updated 2017-08-31; status last verified 2017-08.
• Results first posted 2013-05-27.
• 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

NCT00641641 is a completed, open-label, single-group study sponsored by the Kirby Institute, with enrollment of 16. The recorded study start was 2008-03 and primary completion was 2011-03. The intervention combined tenofovir and emtricitabine, taken orally once per day as a fixed-dose combination, with raltegravir taken orally twice per day.

The primary endpoint was mean change from baseline plasma HIV RNA in log copies/mL, defined as the mean of 12 assessments minus baseline within 48 weeks. The analysis population is described as intention to treat. The numerical primary outcome and its uncertainty are not reported in the registry record. Safety entries list 0 serious adverse events and 0 other adverse events among 16 participants at risk; the death count is not reported in the registry record.