A Study of an Investigational Regimen Combining FDA Approved HIV Drugs in HIV-Infected Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of an Investigational Regimen Combining FDA Approved HIV Drugs in HIV-Infected Subjects (NCT00363142), a randomized phase 3 study. The primary outcome is Percentage of Participants Not Meeting the Definition of Virologic Failure at or Prior to Week 24.

2. Clinical Question

The clinical question is a comparison of regimen-level outcomes under the trial’s assigned treatment groups. It is not a comparison of the two FPV/r200 schedules separately, because the record combines those schedules in one arm. The endpoint counts participants who avoided the specified failure definition by or before Week 24; it is not a direct measure of every aspect of HIV control, safety, or quality of life.

The registry describes the study as evaluating efficacy and safety over 24 weeks. The question addressed by the primary endpoint is therefore narrow: how often participants did not meet the stated virologic-failure criteria under each assigned regimen, using the specified approach to missing and discontinued observations. The record does not report a separate primary estimate for each of the two dosing schedules within FPV/r200.

3. Trial Design

This was a randomized, open-label, parallel-group Phase 3 study. The registry lists 211 participants enrolled, HIV infection as the condition, and a completed status. The recorded study start was 2006-05, and primary completion was 2008-06. The study was sponsored by GlaxoSmithKline.

The trial compared FPV/r100, fosamprenavir/ritonavir 1400/100mg once daily, with FPV/r200, fosamprenavir/ritonavir given as either 700/100mg twice daily or 1400/200mg once daily. Because the FPV/r200 group includes two schedules, the arm-level outcome does not isolate the effect of either schedule on its own. The registry does not report separate randomized groups or separate results for those schedules.

Randomization supports an intended comparison between assigned groups, but the record does not describe the sequence-generation method, allocation concealment, or any stratification factors beyond noting that the primary percentage was estimated with stratification by six randomization strata. Masking was listed as none, so the study was open-label. How that feature was handled in endpoint assessment is not reported in the registry record.

The primary analysis population included participants who received at least one dose of investigational product. The primary endpoint analysis used missing/discontinuation equals failure: missing or discontinued values were counted as failures. The arm counts reported for the primary outcome are 140 for FPV/r100 and 69 for FPV/r200. Details of other analysis populations, participant flow after randomization, and the trial’s original sample-size justification are not reported in the registry record.

The study’s planned duration was 24 weeks according to its brief summary, and the primary endpoint timeframe was Week 24. The listed secondary outcomes cover additional virologic, immunologic, treatment-discontinuation, adverse-event, and laboratory measures. The record does not establish from the information available whether every secondary endpoint was measured or analyzed using the same population or missing-data approach as the primary endpoint.

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: Participants were stratified prior to randomization according to baseline regimen (700 milligrams \[mg\]/100 mg twice a day \[BID\] or 1400 mg/200 mg once a day \[QD\]) and previous regimen (no other prior protease inhibitor \[PI\], non-boosted PI, or boosted PI). Results are reported for the 209 participants (out of 211 enrolled) receiving study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat Exposed (ITT-E) Population. Subjects who received at least one dose of investigational product.

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 Percentage of Participants Not Meeting the Definition of Virologic Failure at or Prior to Week 24, measured over Week 24.

The primary endpoint is the percentage of participants not meeting the definition of virologic failure at or prior to Week 24. Failure was defined as two consecutive plasma HIV-1 RNA measurements greater than 400 copies/milliliter, separated by at least 2 to 4 week. The endpoint therefore summarizes whether each participant met that operational failure rule during the stated period; it does not describe all possible virologic outcomes.

The percentage was estimated with stratification by the six randomization strata using Mantel-Haenszel weights. Missing or discontinued values were treated as failures in the missing/discontinuation equals failure analysis. The analysis population was the Intent-to-Treat Exposed population, defined in the record as participants who received at least one dose of investigational product.

As a general statistical concept, a prespecified binary endpoint makes a comparison interpretable by defining a participant-level event and then comparing the proportions in the randomized groups. An endpoint based on a threshold can be clinically and analytically useful, but it compresses a participant’s measurements into whether the rule was met. The chosen threshold, timing, and handling of missing measurements therefore matter to interpretation. The registry record gives the failure definition and missing-data rule, but further operational details of measurement timing are not reported in the registry record.

7. Results Posted in the Registry

• FPV/r200: 94.2% (65/69) versus 92.1% (129/140) on control; risk difference 2.1 percentage points (95% CI -5.0 to 9.2), risk ratio 1.02 (0.95–1.10); unadjusted two-proportion z-test p = 0.587.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Mean Change From Baseline of log10 Copies/mL Plasma HIV-1 RNA Levels at Week 24, Observed Analysis

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • FPV/r200: mean -0.02 versus -0.01 on control; difference -0.01 (95% CI -0.08 to 0.07), standardized effect d = -0.02; z-test p = 0.852.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between FPV/r200 and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering additional virologic thresholds, change in HIV-1 RNA, CD4+ cell count, discontinuation due to adverse events, adverse events, and lipid measures. The numeric secondary analysis included in the posted results is the observed mean change from baseline in log10 copies/mL of plasma HIV-1 RNA at Week 24. Its recalculated mean difference is -0.007, with a 95% confidence interval from -0.081 to 0.067 and an unadjusted p-value of 0.852. These results do not establish a clear between-group difference in that secondary summary, but they are not a substitute for the primary endpoint analysis.

The remaining named secondary outcomes do not have detailed numeric results in the registry record summarized for this comparison. Consequently, the overall secondary-outcome pattern cannot be characterized across all listed measures. The record includes safety counts, but denominators for those counts are not reported. Counts of adverse events should not be treated as directly comparable rates without the relevant denominators and exposure context.

Secondary outcomes can help describe other dimensions of the trial, but they generally carry less confirmatory weight than a prespecified primary endpoint when many outcomes are examined. As a general statistical explanation, testing many outcomes creates more opportunities for chance findings; multiplicity adjustment or another plan for interpreting multiple tests can help address that issue. Whether multiplicity was controlled, and what hierarchy or testing strategy was prespecified, are not reported in the registry record. The secondary results should therefore be interpreted as supplementary rather than as independent confirmation of the primary comparison.

The primary endpoint and the numeric secondary virologic summary measure related but different features: one is a binary failure-definition outcome, while the other is an average change in a continuous RNA measure among observed data. Their analysis populations and missing-data handling are not necessarily the same. The registry labels the secondary analysis as observed analysis, but further details of its missing-data approach are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Plasma Human Immunodeficiency Virus, Type 1, Ribonucleic Acid (HIV-1 RNA) <400 Copies/mL at Week 24, Time to Loss of Virologic Response (TLOVR) Analysis
• Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24, TLOVR Analysis
• Mean Change From Baseline of log10 Copies/mL Plasma HIV-1 RNA Levels at Week 24, Observed Analysis
• Median Change From Baseline of CD4+ Cell Count at Week 24, Observed Analysis
• Number of Participants Who Discontinued Treatment Due to Adverse Events Through Week 24
• Number of Participants With Grade 2-4 Adverse Events Occurring in Greater Than or Equal to 2% of Subjects Through Week 24
• Percent Change From Baseline in Total Cholesterol, High Density Lipoprotein (HDL), and Triglycerides at Week 24
• Percent Change From Baseline in Low Density Lipoprotein (LDL) at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either met the registry’s virologic-failure definition or did not meet it by or prior to Week 24. The reported endpoint is the percentage who did not meet that definition. The record defines failure as two consecutive plasma HIV-1 RNA measures greater than 400 copies/milliliter, separated by at least 2 to 4 week. Missing or discontinued values were considered failures.

Why use a percentage?

As a general statistical explanation, a percentage expresses the observed number of participants with an outcome relative to the group being analyzed. It is a direct summary for a binary endpoint, but it does not show how close individual measurements were to the threshold or describe the timing and pattern of all measurements. The registry lists 129 participants in the FPV/r100 group and 65 in the FPV/r200 group as not meeting the failure definition, out of primary outcome group counts of 140 and 69, respectively. The posted percentages are 92.1% and 94.2%.

What does stratification do?

The record says the primary percentages were estimated with stratification by the six randomization strata using Mantel-Haenszel weights. In general, stratification accounts for defined groups when estimating an overall comparison, rather than simply ignoring their structure. The record does not identify the six strata or report the individual stratum-specific results, so their contribution to the estimate cannot be assessed from the registry record.

What is a risk difference?

As a general statistical concept, a risk difference subtracts one group’s outcome proportion from the other group’s outcome proportion. It is expressed on the proportion scale and describes an absolute contrast. The unadjusted recalculation reports a risk difference of 0.021 for FPV/r200 relative to FPV/r100. Its 95% confidence interval extends from -0.050 to 0.091. Because the interval crosses zero, it includes both a direction favoring FPV/r200 and a direction favoring FPV/r100, as well as no difference. The recalculation is unadjusted and should not be confused with the stratified primary analysis described in the registry.

How should the confidence interval be understood?

In general, a confidence interval is a range of values compatible with the data under the method used, and it communicates precision as well as direction. It is not a guarantee that the true value lies within the particular interval, nor does it assign probabilities to individual values within that range. A wide interval signals that the estimate is not very precise. The recalculated risk-difference interval includes zero and values on either side, so the data do not pin down the direction of the contrast precisely. The registry-reported interval is on its reported difference-in-percentages scale and should be interpreted separately from the recalculated risk difference.

What does the unadjusted p-value add?

The unadjusted p-value for the recalculated primary comparison is 0.587. In general, a p-value measures how compatible the observed data are with a specified null model, under the analysis assumptions. It does not quantify the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The p-value is unadjusted, and the registry’s sponsor-reported analysis does not list a p-value. It should therefore not be used as a substitute for the effect estimate, its interval, or the reported analysis framework.

Why can over-dispersion matter?

As a general statistical explanation, over-dispersion occurs when variability in the data is greater than a model assumes. If a method assumes less variability than is present, uncertainty can be understated and intervals can be too narrow. The primary endpoint is binary and the reported analysis uses a stratified percentage comparison, but the registry record does not report an over-dispersion assessment or a model-based dispersion parameter. No conclusion about over-dispersion can be drawn from the available record.

What do the secondary summaries represent?

The numeric secondary analysis is a mean change from baseline in log10 copies/mL of plasma HIV-1 RNA at Week 24, using observed analysis. The reported arm means are -0.015 for FPV/r100 and -0.022 for FPV/r200, with standard deviations of 0.388 and 0.13. The unadjusted recalculation gives a mean difference of -0.007, with a 95% confidence interval from -0.081 to 0.067 and an unadjusted p-value of 0.852. In general, a mean summarizes the average change, while the standard deviation describes variation among observations; the mean difference compares the two arm averages. The record labels this outcome as observed analysis, which is distinct from the primary endpoint’s missing/discontinuation equals failure rule. Further details of the observed-analysis population are not reported in the registry record.

The record’s reported primary analysis is categorized as non-inferiority or equivalence and presents a difference in percentages with a 95% confidence interval. The non-inferiority or equivalence margin, the specific decision rule, and a method name are not reported in the registry record. Accordingly, the registry’s classification can be described, but the formal design assumptions and decision process cannot be reconstructed from the posted details.

11. Confidence Intervals and Precision

The primary arm percentages are 92.1% for FPV/r100 and 94.2% for FPV/r200. A percentage alone does not show how uncertain the group comparison is. The unadjusted recalculated risk difference is 0.021, and its 95% confidence interval runs from -0.050 to 0.091. The interval includes zero and extends to both sides of it, indicating that the point estimate does not precisely establish the direction of the contrast. The interval also includes a range of possible differences, so the observed estimates do not establish that the regimens have exactly the same outcome.

The registry-reported difference in percentages is -2.12, with a 95% confidence interval from -9.36 to 5.12. This is the sponsor-reported analysis under the listed order FPV/r100 and FPV/r200; it should not be silently substituted for the recalculated risk difference, which uses a different scale and an unadjusted approach. The record classifies the sponsor analysis as non-inferiority or equivalence, but the margin needed to interpret that objective is not reported in the registry record. The interval therefore cannot be judged against a formal margin from the available information.

As a general statistical explanation, confidence intervals convey uncertainty about an estimated contrast: narrower intervals indicate greater precision, while wider intervals leave more values compatible with the data and method. They do not by themselves determine clinical importance. The primary recalculated interval is compatible with differences favoring either group, and the registry-reported interval also spans zero. The record does not report a prespecified threshold for a clinically important difference.

The arm sizes were 140 and 69 for the primary outcome. Unequal group sizes can affect precision, although the registry record does not provide a precision target or a justification for the realized group sizes. The trial’s original sample-size assumptions, any planned interim analyses, and any target width for the primary confidence interval are not reported in the registry record. The registry’s reported interval and the unadjusted recalculated interval are therefore the available ways to describe uncertainty around the primary contrast.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations express planning requirements as participants per arm, not total participants and not total events. The accompanying curve is a planning illustration of how required group size varies with the effect size used for planning; it does not add a separate observed trial outcome. These calculations use the observed effect as a reference and show illustrations for 100%, 75%, and 50% of that observed effect.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For time-to-event outcomes, the stated convention would be total events, but the primary outcome is not time-to-event, so the figures are participants per arm. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column means the planned group size under those assumptions that would give an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column uses a higher chance of detection and therefore requires more participants under the same planning framework. Smaller effects are harder to distinguish from random variation, so planning for smaller fractions of the observed effect requires more participants per arm. The displayed values should be read as design illustrations, not as a description of what the completed trial achieved. This is not observed power.

Because the calculation is anchored to the observed effect, it is sensitive to the uncertainty in that estimate. It does not show that the original trial was designed around the same effect or assumptions, and the registry record does not report those original design details. The planning figures are therefore useful for understanding how assumptions affect hypothetical group sizes, but they do not establish that the trial was adequately or inadequately sized for its original objective.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.921; treatment proportion p₁ = 0.942; average p̄ = 0.932.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3567 = 0.6991.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3564 = 0.2999.
4. n = (0.6991 + 0.2999)² / (0.0206)² = 2,351.8, rounded up to 2,352 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.921428571428571                          # control proportion
p1 <- 0.942028985507246                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(363142)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 2,352 (80% power), 3,148 (90% power)
 75% of observed effect: n per arm = 4,328 (80% power), 5,793 (90% power)
 50% of observed effect: n per arm = 10,065 (80% power), 13,474 (90% power)
power.prop.test: 2351.8 
Simulated power at n = 2,352 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry-reported primary analysis gives a difference in percentages of -2.12, with a 95% confidence interval from -9.36 to 5.12, for the listed group order FPV/r100 and FPV/r200. It is classified in the record as a non-inferiority or equivalence analysis. No p-value is listed for this analysis, and the non-inferiority or equivalence margin and decision rule are not reported in the registry record.

The unadjusted recalculation instead reports a risk difference of 0.021 for FPV/r200 relative to FPV/r100, with a 95% confidence interval from -0.050 to 0.091 and an unadjusted p-value of 0.587. It is a simple recalculation from the posted arm-level summaries and is not the same analysis as the registry-reported stratified estimate. Differences in scale, group ordering, and analysis approach matter when comparing the figures; one estimate should not be treated as a transcription of the other.

The recalculated estimate is useful as a transparent, unadjusted comparison of the posted percentages, while the registry-reported result is the study’s own stated analysis. The record indicates no discrepancy between the two in its comparison of the posted and reported results. That does not remove the need to distinguish their methods or to know the non-inferiority margin before interpreting the sponsor’s analysis as meeting a formal criterion. The available information does not permit reconstruction of that criterion or its decision process.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint uses a defined missing-data convention: missing or discontinued participants are counted as failures in the missing/discontinuation equals failure analysis. This approach is explicit in the registry description and means that the primary estimate reflects both observed outcomes and this assigned treatment of missing or discontinued values. The registry does not report the number of participants with missing Week 24 measurements or the number who discontinued before Week 24, so the effect of this rule on the estimates cannot be separately assessed.

The primary analysis population is the Intent-to-Treat Exposed population, defined as participants who received at least one dose of investigational product. The primary outcome group counts are 140 and 69. The registry does not report, in the information available for this comparison, detailed participant flow by reason for exclusion, treatment discontinuation, or missingness. It also does not report whether any additional populations were used for sensitivity or supportive analyses.

For the secondary mean-change outcome, the analysis is labeled observed analysis. This is a different stated approach from the primary missing/discontinuation equals failure convention. The handling of missing secondary measurements, the number contributing to each secondary analysis, and whether any imputation or sensitivity analysis was used are not reported in the registry record. The available arm counts for this secondary outcome are 131 and 66, but those counts alone do not explain why participants are absent from the analysis.

The registry lists multiple secondary outcomes. As a general statistical issue, testing many outcomes increases the chance of finding an apparently notable result by chance, even if each individual test uses a conventional threshold. A prespecified hierarchy, family-wise error adjustment, or other multiplicity strategy can affect how secondary findings should be interpreted. Whether such a strategy was planned or used is not reported in the registry record. The record also does not report the full statistical analysis plan, any interim analyses, or the trial’s original sample-size justification.

The primary estimate is stratified by six randomization strata using Mantel-Haenszel weights, but the strata and stratum-specific estimates are not reported. Allocation concealment, sequence generation, and details of endpoint assessment in the open-label setting are also not reported in the registry record. These omissions limit the ability to assess the full analysis process beyond the methods explicitly described.

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

The posted primary results show that 92.1% of participants in FPV/r100 and 94.2% in FPV/r200 did not meet the virologic-failure definition by or before Week 24 under the stated analysis. The unadjusted recalculation estimates a risk difference of 0.021, with a 95% confidence interval from -0.050 to 0.091. The interval includes zero and values on both sides, so the estimated contrast is uncertain in direction and size.

These results do not establish that the regimens are identical. A comparison that does not show a clear difference is not proof of equivalence. The registry labels its own analysis as non-inferiority or equivalence, but the margin and decision rule needed to interpret that label are not reported in the registry record. The sponsor-reported interval alone cannot demonstrate that a prespecified non-inferiority or equivalence criterion was satisfied without knowing the criterion.

The findings apply to the specific primary endpoint, its Week 24 timeframe, the Intent-to-Treat Exposed population, and the missing/discontinuation equals failure rule. They do not establish outcomes beyond Week 24, separate results for the two schedules grouped in FPV/r200, or effects on outcomes not measured in the trial. They also do not describe every aspect of safety or virologic response.

The record’s secondary outcome list indicates that other domains were considered, but numeric results for most of those outcomes are not reported in the registry record summarized for interpretation. The observed mean-change analysis is supplementary and uses a distinct analysis label. It should not be taken as a replacement for the primary endpoint or as confirmation of a broader treatment effect.

Overall, the posted estimates describe the trial’s observed group outcomes and their statistical uncertainty. They do not, by themselves, determine clinical importance, establish a formal non-inferiority conclusion, or support conclusions outside the stated population and follow-up period. No medical recommendation follows from these registry results alone.

17. Why This Trial Matters Statistically

This trial illustrates why the scale and definition of an endpoint matter. The primary outcome is a percentage of participants who did not meet a threshold-based virologic-failure rule, while the secondary mean-change outcome summarizes a continuous RNA measure. These statistics answer related but non-identical questions, and their analysis populations and missing-data rules differ in the registry description.

It also illustrates the distinction between a registry-reported analysis and a simple unadjusted recalculation. The registry describes a stratified analysis and classifies it as non-inferiority or equivalence; the recalculation provides an unadjusted risk difference from posted summary counts. Both can be informative, but they are not interchangeable. The missing non-inferiority or equivalence margin is especially important: without it, a reader cannot assess the formal criterion that gives that type of analysis its meaning.

The confidence intervals offer a more complete view than a point estimate or p-value alone. The unadjusted primary interval spans zero and a range of values in both directions. This makes precision and uncertainty central to interpretation rather than allowing the observed percentages to be read as decisive evidence of a difference or of equivalence.

The study also shows how the definition of the analysis population and handling of missing outcomes shape a result. The primary analysis includes participants who received at least one dose and counts missing or discontinued values as failures. Those choices are part of the estimand being described, not mere technical details. Their implications cannot be fully assessed without participant-flow and missingness information.

Finally, the grouped comparator combines two dosing schedules. The arm-level result cannot identify whether either schedule separately accounts for the observed group outcome. Recognizing that limitation prevents overinterpretation of an aggregate comparison.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The comparator FPV/r200 combines fosamprenavir/ritonavir 700/100mg twice daily and 1400/200mg once daily. The registry does not report separate primary outcome estimates for these schedules, so the arm-level result cannot identify their individual contributions.

The primary endpoint relies on a threshold rule requiring two consecutive plasma HIV-1 RNA measurements greater than 400 copies/milliliter, separated by at least 2 to 4 week. The record does not provide further detail on measurement schedules or how unavailable measurements affected whether a pair of consecutive results could be evaluated. Missing or discontinued values were treated as failures, but the counts and reasons for missingness or discontinuation are not reported in the registry record.

The study was open-label, with masking listed as none. The record does not describe endpoint-assessment procedures or safeguards against potential effects of the unmasked design. It also does not provide allocation concealment or randomization-sequence details. The primary analysis is described as stratified by six randomization strata, but the strata and stratum-specific results are not reported.

The reported non-inferiority or equivalence analysis lacks a stated margin and decision rule in the available record. The trial’s original sample-size justification and assumptions are also not reported. These omissions prevent a full assessment of how the study was designed to support its stated analytical classification.

Numerical results are not available for most listed secondary outcomes in the record summarized for this analysis. The secondary mean-change outcome is labeled observed analysis, but its missing-data details are not reported. The registry does not report whether multiplicity was addressed, whether interim analyses occurred, or the complete statistical analysis plan. These limitations constrain interpretation of both the primary conclusion and the broader set of outcomes.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of an Investigational Regimen Combining FDA Approved HIV Drugs in HIV-Infected Subjects — NCT00363142.
• Registry record last updated 2010-11-05; status last verified 2010-10.
• Results first posted 2009-09-24.
• 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.

22. Record Summary

NCT00363142 is a completed, randomized, open-label, parallel-group Phase 3 study sponsored by GlaxoSmithKline. The registry reports enrollment of 211 participants and a 24-week evaluation of fosamprenavir/ritonavir regimens in people with HIV infection.

The primary comparison was between FPV/r100, 1400/100mg once daily, and FPV/r200, either 700/100mg twice daily or 1400/200mg once daily. The primary endpoint was the percentage not meeting the virologic-failure definition at or prior to Week 24. The posted percentages were 92.1% and 94.2%, respectively. The unadjusted recalculated risk difference was 0.021, with a 95% confidence interval from -0.050 to 0.091.

The registry also reports a sponsor analysis classified as non-inferiority or equivalence, but its margin is not reported in the registry record. Missing or discontinued primary endpoint values were counted as failures. Secondary outcomes span virologic, immunologic, safety, and laboratory measures; detailed numeric results for most are not reported in the registry record.