This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings (NCT00084136), a randomized phase 4 study. The primary outcome is Time to Treatment Failure (PI Comparison).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00084136 |
| Phase | Phase 4 |
| Condition | HIV Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 1571 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled people with HIV starting their first antiretroviral treatment regimen. The primary endpoint population is described as ITT, with study treatment status and history ignored. Recruitment included resource-limited areas in Africa, Asia, South America, and Haiti, as well as the United States. The registry does not give further eligibility details in this record.
Intervention
The study compared three-drug combinations. The named regimens were ZDV/3TC+EFV, ddI+FTC+ATV, and TDF/FTC+EFV. The ddI+FTC+ATV combination included enteric-coated didanosine, emtricitabine, and atazanavir; the other two combinations included efavirenz with their listed nucleoside components.
Comparator
The registry describes a comparison involving a protease-inhibitor regimen and comparisons involving non-nucleoside reverse transcriptase inhibitor regimens. Its study hypothesis was that each once-daily combination, PI-based or NNRTI-based, would not have inferior efficacy to the twice-daily NNRTI-based combination. The exact arm-to-arm contrast for the listed primary endpoint is not reported in the registry record.
Primary question
For the PI comparison, the primary endpoint was time to treatment failure. Failure was defined using virologic failure, specified AIDS-defining diagnoses, or death. The question is therefore about the time until the first qualifying event under the trial’s definitions, not simply a viral-load measurement at one visit. A primary endpoint estimate or treatment-effect result is not reported in the registry record.
3. Trial Design
PEARLS was a randomized, open-label, parallel-group phase 4 trial. The registry records enrollment of 1571 and describes three initial three-drug antiretroviral combinations: ZDV/3TC+EFV, ddI+FTC+ATV, and TDF/FTC+EFV. Because masking was listed as none, the study was open-label; the registry does not describe any additional masking procedures.
The trial’s stated hypothesis concerned noninferiority: each once-daily combination, whether PI-based or NNRTI-based, was hypothesized not to have inferior efficacy compared with a twice-daily NNRTI-based combination. The record does not state a noninferiority margin, nor does it identify the specific arm contrast used for the primary PI comparison. Those details are not reported in the registry record.
Participants were recruited in resource-limited areas in Africa, Asia, South America, and Haiti, and also in the United States. The registry lists HIV Infections as the condition and describes the participants as starting their first HIV treatment regimens. The listed start date is 2005-05, primary completion is 2010-05, and the status is completed.
The primary endpoint is labelled Time to Treatment Failure (PI Comparison). Its follow-up description states that virologic failure counted starting 14 weeks following randomization, disease progression starting 12 weeks following randomization, and death at any time following randomization. Follow-up for this endpoint continued until the ddI+FTC+ATV arm closed on May 22, 2008. The registry lists secondary outcomes addressing treatment discontinuation, immunologic failure, CD4 count, adverse events, and viral-load response, among other measures.
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: HIV-infected, treatment-naive men and women, at least 18 years of age with CD4+ count \<300 cells/mm\^3.
PI Comparison
| Stage | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV |
|---|---|---|---|
| STARTED | 519 | 526 | 0 |
| COMPLETED | 464 | 479 | 0 |
| NOT COMPLETED | 55 | 47 | 0 |
Reasons for not completing this period:
| Reason | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV |
|---|---|---|---|
| Death | 10 | 9 | 0 |
| Lost to Follow-up | 11 | 8 | 0 |
| Withdrawal by Subject | 33 | 30 | 0 |
| Clinic site closed | 1 | 0 | 0 |
NRTI Comparison
| Stage | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV |
|---|---|---|---|
| STARTED | 519 | 0 | 526 |
| COMPLETED | 418 | 0 | 444 |
| NOT COMPLETED | 101 | 0 | 82 |
Reasons for not completing this period:
| Reason | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV |
|---|---|---|---|
| Death | 20 | 0 | 18 |
| Lost to Follow-up | 14 | 0 | 12 |
| Withdrawal by Subject | 54 | 0 | 38 |
| Clinic site closed | 12 | 0 | 14 |
| Not reason above | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: ITT (study treatment status and history ignored); censoring time was latest study visit week where plasma HIV-1 RNA was measured.
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.
| Characteristic | Unit | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV | Total |
|---|---|---|---|---|---|
| Participants analysed | 519 | 526 | 526 | 1571 | |
| Age, Continuous | years | 35 (SD 9) | 35 (SD 8) | 35 (SD 9) | 35 (SD 9) |
| Age, Customized: Between 18 and 29 years | participants | 141 | 146 | 146 | 433 |
| Age, Customized: Between 30 and 39 years | participants | 244 | 221 | 225 | 690 |
| Age, Customized: Between 40 and 49 years | participants | 100 | 129 | 116 | 345 |
| Age, Customized: At least 50 years | participants | 34 | 30 | 39 | 103 |
| Sex: Female, Male: Female | Participants | 241 | 256 | 242 | 739 |
| Sex: Female, Male: Male | Participants | 278 | 270 | 284 | 832 |
| Region of Enrollment: Brazil | participants | 79 | 76 | 76 | 231 |
| Region of Enrollment: Haiti | participants | 35 | 32 | 33 | 100 |
| Region of Enrollment: India | participants | 81 | 86 | 88 | 255 |
| Region of Enrollment: Malawi | participants | 74 | 74 | 73 | 221 |
| Region of Enrollment: Peru | participants | 42 | 48 | 44 | 134 |
| Region of Enrollment: South Africa | participants | 70 | 70 | 70 | 210 |
| Region of Enrollment: Thailand | participants | 32 | 33 | 35 | 100 |
| Region of Enrollment: United States | participants | 70 | 70 | 70 | 210 |
| Region of Enrollment: Zimbabwe | participants | 36 | 37 | 37 | 110 |
| CD4 count, Continuous | cells/mm^3 | 163 (SD 85) | 167 (SD 83) | 155 (SD 81) | 162 (SD 83) |
| CD4 count, Categorical: < 50 cells/mm^3 | participants | 68 | 63 | 69 | 200 |
| CD4 count, Categorical: Between 50 and 99 cells/mm^3 | participants | 70 | 77 | 82 | 229 |
| CD4 count, Categorical: Between 100 and 199 cells/mm^3 | participants | 174 | 161 | 193 | 528 |
| CD4 count, Categorical: Between 200 and 249 cells/mm^3 | participants | 104 | 128 | 107 | 339 |
| CD4 count, Categorical: Between 250 and 299 cells/mm^3 | participants | 103 | 97 | 75 | 275 |
| Plasma HIV-1 RNA, Continuous | log10 copies/mL | 5.0 (4.6 to 5.4) | 5.1 (4.5 to 5.5) | 5.0 (4.5 to 5.5) | 5.0 (4.6 to 5.5) |
| Plasma HIV-1 RNA, Categorical: <= 400 copies/mL | participants | 3 | 6 | 3 | 12 |
| Plasma HIV-1 RNA, Categorical: Between 400 and 4000 copies/mL | participants | 22 | 19 | 14 | 55 |
| Plasma HIV-1 RNA, Categorical: Between 4001 and 40,000 copies/mL | participants | 103 | 119 | 124 | 346 |
| Plasma HIV-1 RNA, Categorical: Between 40,001 and 400,000 copies/mL | participants | 311 | 283 | 284 | 878 |
| Plasma HIV-1 RNA, Categorical: Between 400,001 and 749,999 copies/mL | participants | 45 | 58 | 55 | 158 |
| Plasma HIV-1 RNA, Categorical: >= 750,000 copies/mL | participants | 35 | 40 | 46 | 121 |
| Plasma HIV-1 RNA, Categorical: Missing | participants | 0 | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Treatment Failure (PI Comparison), measured over Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up until ddI+FTC+ATV arm closed (May 22, 2008)..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | weeks |
| Endpoint classification | not reduced to a single comparison |
Time to treatment failure measures the interval from randomization to the earliest qualifying event. For the PI comparison, the registry defines the event as the scheduled week of the first plasma sample meeting virologic-failure criteria, the scheduled week of a qualifying AIDS-defining diagnosis, or the date of death from any cause. Virologic failure required two consecutive plasma HIV-1 RNA values of 1,000 copies/mL or higher, regardless of whether antiretroviral medications were being taken at the time. Disease progression was based on specified AIDS-defining diagnoses and was not counted if attributed to immune reconstitution inflammatory syndrome, as reviewed by chairs.
This type of endpoint is used to represent how long participants remain without a defined failure event, while combining clinically distinct events under a prespecified composite definition. It differs from comparing viral load at a single scheduled visit: it incorporates when the first qualifying event occurs. Plasma was drawn every 8 weeks, although confirmation samples could be drawn earlier. The endpoint description specifies censoring at the latest study-visit week when plasma HIV-1 RNA was measured. Follow-up ended when the ddI+FTC+ATV arm closed on May 22, 2008.
The registry identifies an ITT population for this endpoint, with study treatment status and history ignored. It does not report a primary endpoint estimate, confidence interval, or treatment-comparison result. Therefore, the endpoint definition can be described, but the registry record does not permit a quantitative assessment of the observed time-to-failure contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies time to treatment failure for the PI comparison as the primary outcome, but does not report a numerical estimate of that outcome or the treatment contrast. It also does not report a confidence interval or a primary endpoint hypothesis-test result. As a result, the record does not establish the direction, size, or precision of the primary comparison. No conclusion about whether one regimen had more or less treatment failure can be drawn from the endpoint information alone.
The trial’s stated hypothesis was that each once-daily regimen would not have inferior efficacy to the twice-daily NNRTI-based regimen. This describes the intended noninferiority question, not an observed finding. A noninferiority conclusion requires a specified margin and an analysis of the treatment contrast against that margin. The margin and the detailed primary analysis are not reported in the registry record, and no primary result is available to assess against them.
The endpoint combines virologic failure, specified disease progression, and death. A treatment contrast on this composite would summarize time to the first of these events under the trial definitions; it would not, by itself, show how each event type contributed. The registry record does not report component-specific primary outcome results. The listed secondary outcomes cover other aspects of treatment and response, but their presence in the record is not a substitute for the missing primary endpoint estimate.
The registry does provide serious and other adverse-event counts for the three groups, along with several frequently listed serious-event terms. These safety figures describe the posted event information, not the primary efficacy comparison. They should not be read as a complete account of all possible harms or as a comparison adjusted for differences in follow-up. The record does not give a primary endpoint result that could be weighed alongside those safety data.
The stated total enrollment and randomized design describe the scale and structure of the trial, but enrollment alone does not determine the precision of a time-to-event estimate. Precision depends on the observed event information and the analysis. Since those primary endpoint results are not reported in the registry record, no estimate of the treatment effect’s precision is possible from this record.
9. Statistical Methods Explained
What does a time-to-event endpoint represent?
In general, a time-to-event analysis considers both whether a defined event occurred and when it occurred during follow-up. A participant who has not had the event by the end of observed follow-up may contribute information up to that point without being treated as though the event occurred. This is called censoring. It is useful when participants have different lengths of observation or when the event has not occurred for everyone by the end of follow-up.
For this trial’s primary endpoint, the event is a composite: virologic failure, qualifying disease progression, or death. The endpoint time is the time to the earliest qualifying event. The record defines the event criteria and says censoring time was the latest study-visit week at which plasma HIV-1 RNA was measured. It does not report the number of primary events, the estimated time-to-event contrast, or the analysis method used to estimate it.
Why define events in detail?
In general, operational definitions make an endpoint more reproducible. Here, virologic failure required two consecutive plasma HIV-1 RNA values at or above the stated threshold, and the record specified which diagnoses counted as disease progression. It also specified how diagnoses attributed to immune reconstitution inflammatory syndrome were handled and included death from any cause. These rules identify what qualifies as an event; they do not show how often each event occurred or which component drove a treatment contrast.
The timing rules also matter. The registry says virologic failure counted starting 14 weeks following randomization and disease progression starting 12 weeks following randomization, while death counted at any time following randomization. Plasma was drawn every 8 weeks, except that confirmation samples could be drawn earlier. These details affect how event times are assigned and interpreted. The record does not describe further adjudication procedures beyond the stated review by chairs for the specified diagnoses.
What does the confidence interval mean?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. For a treatment comparison, the interval helps readers assess which effect sizes remain compatible with the observed data and analysis. The registry lists a 95% confidence interval as the endpoint’s dispersion measure, but does not report the interval or the estimate it would accompany. Therefore, the precision of the primary comparison cannot be evaluated from the registry record.
How does the stated noninferiority question differ from a superiority question?
In general, a noninferiority analysis asks whether the evidence rules out a loss of efficacy larger than a prespecified margin. The margin defines the largest difference that would still meet the noninferiority criterion. The registry’s hypothesis says that each once-daily regimen would not have inferior efficacy to a twice-daily NNRTI-based regimen. However, the noninferiority margin, exact primary contrast, and decision rule are not reported in the registry record. Without those details and the primary result, the hypothesis cannot be evaluated statistically.
What does the ITT description tell readers?
The primary population is labelled ITT, with study treatment status and history ignored. In general, an intention-to-treat approach aims to analyze participants according to their randomized assignment, rather than restricting analysis to those who continued the assigned treatment. The registry wording identifies the population used for the endpoint but does not report the number of participants included in the primary analysis, how all missing measurements were handled, or whether additional analysis populations were used.
The endpoint description gives one specific rule for censoring: the censoring time was the latest study-visit week where plasma HIV-1 RNA was measured. Censoring can affect time-to-event estimates if participants’ subsequent event status is unknown. In general, time-to-event methods rely on assumptions about how censoring relates to the chance of the event. The registry record does not describe checks of those assumptions or any sensitivity analyses.
What can be inferred from the study design?
Randomization is intended, in general, to make treatment groups comparable at assignment with respect to measured and unmeasured characteristics. Open-label status means the registry lists no masking. In general, knowledge of treatment assignment can influence care or reporting, so blinded outcome assessment may be relevant; whether it was used for any outcomes is not reported in the registry record. No additional claims about the conduct or analysis should be inferred from the design labels alone.
The record lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the illustration is described as a total number of events using Schoenfeld; other illustrations are described as participants per arm. These are planning illustrations, not observed power, and the record does not give the values needed to describe a particular planning scenario. The trial’s own sample-size justification is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 18 outcome measures and 2 analyses. It names a primary endpoint and several secondary outcomes, including treatment discontinuation, immunologic failure, CD4 count change, adverse events, viral load below the stated threshold, and measures of loss of virologic response. The presence of multiple outcomes and analyses raises the general issue of multiplicity: when many hypotheses are assessed, the chance of at least one apparently notable result can increase unless the analysis plan accounts for this.
Whether multiplicity was controlled, and by what method, is not reported in the registry record. The record also does not report a hierarchy among secondary outcomes, a family of hypotheses, or which outcomes were intended to support confirmatory conclusions. No statistical analysis plan or interim-analysis approach is described in the registry record, so such procedures should not be assumed.
The primary endpoint population is labelled ITT, with study treatment status and history ignored. The record gives a censoring rule based on the latest study-visit week with a plasma HIV-1 RNA measurement. It does not report the primary analysis population size, the extent of missing endpoint data, or how missing data other than this censoring rule were addressed. It also does not report sensitivity analyses for missingness or censoring.
In general, missingness and censoring matter because participants whose outcome information is incomplete may differ from those with continued observation. The record’s stated rules help define the endpoint analysis, but do not establish whether missingness assumptions were assessed. The noninferiority margin and detailed primary analysis plan are not reported in the registry record, limiting assessment of whether the intended question was tested as planned.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| ZDV/3TC+EFV | 86 | 519 | 16.6% |
| ddI+FTC+ATV | 84 | 526 | 16.0% |
| TDF/FTC+EFV | 55 | 526 | 10.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ZDV/3TC+EFV | 481 of 519 |
| ddI+FTC+ATV | 521 of 526 |
| TDF/FTC+EFV | 489 of 526 |
Most frequent serious adverse event terms
| Event term | Organ system | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV |
|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 17 of 519 | 8 of 526 | 2 of 526 |
| Anaemia | Blood and lymphatic system disorders | 12 of 519 | 2 of 526 | 2 of 526 |
| Hepatitis | Hepatobiliary disorders | 4 of 519 | 5 of 526 | 1 of 526 |
| Blood bilirubin increased | Investigations | 0 of 519 | 8 of 526 | 2 of 526 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 3 of 519 | 5 of 526 | 2 of 526 |
| Hyperbilirubinaemia | Hepatobiliary disorders | 1 of 519 | 8 of 526 | 0 of 526 |
| Neutrophil count decreased | Investigations | 5 of 519 | 4 of 526 | 0 of 526 |
| Suicide attempt | Psychiatric disorders | 1 of 519 | 2 of 526 | 5 of 526 |
| Pancreatitis | Gastrointestinal disorders | 2 of 519 | 5 of 526 | 0 of 526 |
| Gastroenteritis | Infections and infestations | 2 of 519 | 4 of 526 | 1 of 526 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ZDV/3TC+EFV | ddI+FTC+ATV | TDF/FTC+EFV |
|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | 269 of 519 | 304 of 526 | 289 of 526 |
| Alanine aminotransferase increased | Investigations | 220 of 519 | 261 of 526 | 265 of 526 |
| Blood albumin abnormal | Investigations | 174 of 519 | 188 of 526 | 188 of 526 |
| Blood bilirubin increased | Investigations | 44 of 519 | 397 of 526 | 39 of 526 |
| Pyrexia | General disorders | 96 of 519 | 120 of 526 | 112 of 526 |
| Neutrophil count decreased | Investigations | 114 of 519 | 93 of 526 | 103 of 526 |
| Cough | Respiratory, thoracic and mediastinal disorders | 81 of 519 | 97 of 526 | 106 of 526 |
| Headache | Nervous system disorders | 78 of 519 | 90 of 526 | 91 of 526 |
| Haemoglobin decreased | Investigations | 88 of 519 | 90 of 526 | 79 of 526 |
| Blood phosphorus decreased | Investigations | 75 of 519 | 87 of 526 | 80 of 526 |
Serious events with the highest arm-level rate: neutropenia (3.3%), anaemia (2.3%), hyperbilirubinaemia (1.5%), blood bilirubin increased (1.5%), neutrophil count decreased (1.0%).
The registry reports serious-event affected counts and other-event affected counts for each treatment group. For ZDV/3TC+EFV, the serious-event figures are 86 affected and 519 at risk; the other-event figures are 481 affected and 519 at risk. For ddI+FTC+ATV, the corresponding figures are 84 and 526 for serious events, and 521 and 526 for other events. For TDF/FTC+EFV, the figures are 55 and 526 for serious events, and 489 and 526 for other events. These are registry counts and at-risk figures, not adjusted comparative estimates.
The listed top serious-event terms include Neutropenia at 3.3%, Anaemia at 2.3%, Hyperbilirubinaemia at 1.5%, Blood bilirubin increased at 1.5%, Neutrophil count decreased at 1.0%, and Pancreatitis at 1.0%. The registry does not provide further detail in this record about event timing, severity grading beyond the serious-event listing, or treatment-group breakdowns for these terms. Death counts are recorded as null, so death figures are not reported in the registry record.
In general, adverse-event counts describe what was recorded under the registry’s categories; they do not by themselves establish that a treatment caused an event or provide a complete comparative safety analysis. The figures should be interpreted alongside their definitions and follow-up, which are not fully detailed for these summaries in the registry record.
12. What the Result Does, and Does Not, Mean
The trial record establishes that a randomized, open-label, parallel-group comparison of three initial antiretroviral combinations was conducted, and it identifies a time-to-treatment-failure endpoint for the PI comparison. It also states the study’s noninferiority hypothesis and defines the principal event components. These design and endpoint details clarify the question the trial intended to address.
However, the registry record does not report a numerical primary endpoint result, its confidence interval, or a test result. It therefore does not show the observed size or direction of the primary treatment contrast, or how precisely that contrast was estimated. The stated noninferiority hypothesis cannot be treated as a finding. The record does not give the margin needed to assess a noninferiority claim, either.
The serious and other adverse-event figures provide descriptive safety information by group, and several serious-event terms are listed with percentages. They do not replace the missing primary efficacy result, and they should not be interpreted as a complete adjusted comparison. The registry does not supply enough detail in this record to assess whether differences in exposure or follow-up affected those event summaries.
In general, a trial result is interpreted in light of its estimate, uncertainty, endpoint definition, analysis population, and design. Here, the endpoint definition and broad design are described, but the primary estimate and key inferential details are absent. The appropriate reading is therefore limited: the registry documents the study question and some design and safety information, but it does not report the primary outcome evidence needed to judge the treatment comparison.
13. Why This Trial Matters Statistically
This trial is statistically notable for posing a noninferiority question across once-daily and twice-daily antiretroviral combinations in a randomized, open-label, parallel-group design. Noninferiority questions require careful specification: the comparator, endpoint, noninferiority margin, analysis population, and decision rule all affect interpretation. The registry states the broad hypothesis and identifies time to treatment failure for the PI comparison, but the exact contrast and margin are not reported in the registry record.
The primary endpoint also illustrates how a composite time-to-event outcome depends on detailed event rules. Virologic failure, qualifying disease progression, and death are different types of outcomes, but the endpoint combines them by counting the earliest qualifying event. That construction can provide a single time-to-event measure, while leaving the contribution of individual components important to interpretation. Component-specific primary findings are not reported in the registry record.
The trial’s ITT description and censoring rule are relevant to understanding the analysis population and follow-up. In general, these decisions influence which observations contribute to an estimate and how incomplete follow-up is handled. The record does not provide enough detail to assess missing-data assumptions, sensitivity analyses, or the full statistical analysis plan.
Finally, the distinction between a trial’s stated objective and its reported evidence is essential. A hypothesis, randomized design, enrollment figure, and endpoint definition do not establish a treatment effect. Since the registry does not report the primary estimate or its uncertainty, this record is useful for understanding the intended statistical question, but it cannot support a quantitative conclusion about that question.
14. 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 main limitation for interpreting the primary outcome is that the registry record does not report its estimate, confidence interval, or statistical test result. The exact treatment contrast for the PI comparison is also not reported in the registry record. Although the study hypothesis describes a noninferiority objective, the noninferiority margin and decision rule are absent, so the intended criterion cannot be evaluated.
The endpoint combines virologic failure, specified disease progression, and death. The record defines these components but does not report their separate contributions to the primary outcome. It also does not report the number of primary events or the amount of censoring. The stated ITT population and censoring rule do not answer how all missing measurements were handled or whether sensitivity analyses were conducted.
The trial was open-label, with masking listed as none. The record does not describe whether outcome assessment was masked or whether additional procedures were used to reduce bias. The recruitment description spans several regions, but this record does not provide site-level results or further participant characteristics that would permit assessment of variation across settings.
The safety summary is limited to serious and other affected counts, at-risk figures, and a list of top serious-event terms. Death values are null, and further detail about the safety definitions, timing, and group-specific term counts is not reported in the registry record. The multiplicity approach, interim analyses, and the trial’s own sample-size justification are also not reported. These limitations constrain interpretation of both efficacy and safety information in this record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings — NCT00084136.
- Registry record last updated 2018-10-10; status last verified 2018-09.
- Results first posted 2011-08-09.
- 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.
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18. Record Summary
The PEARLS registry record describes a completed phase 4 randomized, open-label, parallel-group trial of three initial antiretroviral combinations in people with HIV beginning treatment. Enrollment was 1571. Recruitment included resource-limited areas in Africa, Asia, South America, and Haiti, as well as the United States.
The primary endpoint for the PI comparison was time to treatment failure, defined by virologic failure, qualifying disease progression, or death. The record states a noninferiority hypothesis for once-daily regimens compared with a twice-daily NNRTI-based regimen. It also lists secondary outcomes and serious and other adverse-event summaries.
A primary endpoint estimate, confidence interval, exact primary contrast, and noninferiority margin are not reported in the registry record. Consequently, the registry information describes the trial question and selected design and safety details, but does not provide the primary outcome evidence needed to assess the treatment comparison.