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 Safety and Tolerability of AAV8 Delivery of a Broadly Neutralizing Antibody in Adults Living With HIV: a Phase 1, Dose-escalation Trial (NCT03374202), a non-randomized phase 1 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of AAV8-VRC07 Product Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03374202 |
| Phase | Phase 1 |
| Condition | HIV-1 Infected Adults With Controlled Viremia |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
Adults with HIV-1 infection and controlled viremia who were receiving antiretroviral treatment. The safety endpoint population included enrolled participants who received AAV8-VRC07 and provided safety data through a diary card.
Intervention
AAV8-VRC07, a recombinant AAV8 vector intended to direct cells to produce the VRC07 HIV-1 neutralizing antibody. The study used intramuscular administration and included three dose groups: 5 x 10^10 vg/kg, 5 x 10^11 vg/kg, and 2.5 x 10^12 vg/kg.
Comparator
The registry describes a non-randomized, parallel-group, dose-escalation study with no masking. It does not describe a randomized control group. The dose groups are not like-for-like control arms, so comparisons across them should be interpreted as descriptive rather than as controlled treatment effects.
Primary question
The primary endpoint counts participants reporting local reactogenicity signs or symptoms during the 7 days after product administration. The study also sought to assess safety and whether cells produced VRC07 antibody. The registry record does not report the primary endpoint’s symptom counts or severity findings, so the posted information does not establish how often local symptoms occurred.
3. Trial Design
NCT03374202 is a Phase 1, non-randomized, unmasked, parallel-group dose-escalation trial. The registry lists enrollment of 10 and describes three groups receiving AAV8-VRC07 at different dose levels: 5 x 10^10 vg/kg, 5 x 10^11 vg/kg, and 2.5 x 10^12 vg/kg. Administration was intramuscular. Participants received the study product on Day 0, according to the group descriptions.
The study population was adults with HIV-1 infection and controlled viremia who were receiving antiretroviral treatment. The brief summary describes eligibility as adults ages 18-65, in general good health, and taking the same HIV medicine for at least 3 months. Participants were screened in a different protocol. The registry describes ongoing visits for physical examination, medical history, blood collection, and possible saliva collection, with five years of total study participation.
The primary outcome was the number of participants reporting local reactogenicity signs and symptoms during the 7 days after product administration, at approximately Week 1. Participants recorded solicited symptoms on diary cards, which were reviewed with clinic staff. The study also lists CD4 cell counts, viral load, and serum VRC07 antibody concentration among secondary outcomes. The registry record lists 13 outcome measures, but does not report results for the primary endpoint or the secondary outcomes in the information.
Because assignment was non-randomized and the dose groups were not a control comparison, differences between groups cannot be interpreted as unbiased estimates of dose effects. The registry record does not report a statistical analysis plan or an explanation of how dose escalation was governed.
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.
One Year Follow Up
| Stage | Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) |
|---|---|---|---|
| STARTED | 3 | 3 | 4 |
| Received Study Product | 3 | 3 | 4 |
| COMPLETED | 3 | 3 | 4 |
| NOT COMPLETED | 0 | 0 | 0 |
Five Year Long Term Follow Up
| Stage | Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) |
|---|---|---|---|
| STARTED | 3 | 3 | 4 |
| COMPLETED | 2 | 0 | 0 |
| NOT COMPLETED | 1 | 3 | 4 |
Reasons for not completing this period:
| Reason | Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) |
|---|---|---|---|
| Long Term Follow Up Ongoing | 1 | 2 | 4 |
| Death | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Population included all enrolled participants who received AAV8-VRC07 and provided safety data (via diary card).
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.
Population: Population included all enrolled participants.
| Characteristic | Unit | Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 4 | 10 | |
| Age, Continuous | years | 50.7 (SD 12.9) | 34.7 (SD 15.5) | 43.0 (SD 12.8) | 42.8 (SD 13.7) |
| Age, Customized: 21-30 years | Participants | 0 | 2 | 0 | 2 |
| Age, Customized: 31-40 years | Participants | 1 | 0 | 2 | 3 |
| Age, Customized: 41-50 years | Participants | 0 | 0 | 0 | 0 |
| Age, Customized: 51-60 years | Participants | 2 | 1 | 2 | 5 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 2 | 2 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 2 | 8 |
| Race/Ethnicity, Customized: Black or African American | Participants | 1 | 1 | 3 | 5 |
| Race/Ethnicity, Customized: White | Participants | 2 | 2 | 1 | 5 |
| Race/Ethnicity, Customized: Hispanic/Latino | Participants | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Non-Hispanic/Latino | Participants | 3 | 3 | 3 | 9 |
| Weight (kg) | kg | 75.5 (SD 8.6) | 74.5 (SD 1.6) | 83.1 (SD 8.8) | 78.2 (SD 7.8) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of AAV8-VRC07 Product Administration, measured over 7 days after AAV8-VRC07 product administration, at approximately Week 1.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants reporting local reactogenicity signs or symptoms during the 7 days after AAV8-VRC07 administration. A participant was counted once for each symptom, at the worst severity reported during the period, even if the symptom occurred more than once or at different severities. The measure of “Any Local Symptom” refers to participants reporting any local symptom at the worst severity.
This endpoint is used to describe short-term local tolerability after administration. Reporting both the number of participants affected and symptom severity can distinguish whether a symptom was reported from how severe the report was under the study’s grading approach. The registry says grading used the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
The registry specifies the outcome definition and safety population, but does not report the actual local symptom counts or severity results. The primary endpoint therefore cannot be quantified from the information in the registry record. It also does not, by itself, answer whether VRC07 antibody was produced, or describe longer-term safety; those questions relate to other outcomes and follow-up information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial’s design and defines its primary safety outcome, but the available record does not state the primary endpoint results. It does not report how many participants experienced any local symptom, which symptoms were reported, or how those symptoms were graded. As a result, the primary endpoint cannot be interpreted as a numerical estimate of local reactogenicity from the record.
The posted serious adverse event information is presented by dose group. Group 1 lists 0 serious events among 3 at risk; Group 2 lists 1 among 3; and Group 3 lists 0 among 4. The registry also reports other adverse events for the groups: 2 among 3, 2 among 3, and 4 among 4, respectively. These are descriptive counts. Because allocation was non-randomized and there is no like-for-like control group, differences across dose groups do not provide a controlled estimate of the effect of dose.
The record lists 1 death in Group 2 and 0 in each of the other groups. It does not state the cause of death or establish whether it was related to the study product. A death reported in a study safety record should not be interpreted as evidence of causation without information about attribution and clinical context. The registry record does not report those details.
The top serious event term listed is Overdose, with 33.3%. The record does not give enough context in the available information to interpret that percentage as a group-specific risk or to determine the circumstances of the event. It should be read as a registry-reported term and percentage, not as a causal conclusion.
In general, counts are most informative when read alongside their denominators, outcome definitions, follow-up period, and completeness of reporting. Here, the serious and other event counts are reported by group, while the primary local reactogenicity results are not reported. The safety population for the primary endpoint required receipt of AAV8-VRC07 and diary-card safety data. The registry record does not describe missing diary data or provide a participant-level account of follow-up completeness. These gaps limit how precisely the posted safety information can characterize the experience of the enrolled population.
No treatment-effect conclusion should be drawn from the descriptive safety counts. The registry record does not report comparative estimates, confidence intervals, or an inferential analysis for these outcomes.
9. Statistical Methods Explained
The methods described by the registry support a descriptive reading of this Phase 1 safety study. Its primary outcome is a count of participants with reported local reactogenicity, rather than a continuous measurement or a time-to-event estimate. A count records how many participants met an outcome definition; it does not describe symptom duration or provide a measure of severity unless severity is reported separately. The registry defines the endpoint and grading approach, but does not report the observed primary outcome counts.
What does a count measure?
For a binary outcome, each participant is classified according to whether the specified event was reported during the stated observation period. The resulting count depends on the event definition, population included, and completeness of observation. In this trial, the local symptom outcome covers the 7 days after administration, and diary cards were reviewed at a follow-up visit. A participant could contribute to the count for each symptom, while the “Any Local Symptom” measure counts participants reporting any local symptom at the worst severity. These definitions matter when interpreting a count: symptom-specific counts and the count for any symptom are not interchangeable.
Why do group counts not establish a dose effect?
General: a randomized comparison is designed to make treatment groups comparable in expectation, while a non-randomized comparison can reflect differences between groups as well as differences in exposure. This registry describes non-randomized dose groups and does not identify a control group. Accordingly, a difference in observed event counts across dose levels would be descriptive and could not, on its own, isolate the effect of dose. The registry record does not report an adjusted comparative analysis or explain the allocation process in enough detail to support a causal interpretation.
How should uncertainty be understood?
General: a confidence interval describes a range of estimates compatible with the observed data under a specified statistical model. It conveys sampling uncertainty and is not a guarantee that the true value lies within the interval. With small groups, estimates of event frequency can be imprecise; a small change in the observed count can materially change the estimated frequency. The posted information does not report confidence intervals for the safety counts, so their statistical precision cannot be assessed from the registry record.
The sample-size material is described as 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 uses stated fractions of the observed effect to illustrate planning for participants per arm for 80% power or 90% power. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The registry record does not report the trial’s own sample-size justification, and no numeric planning values are stated in the record information. A time-to-event calculation is not relevant to the primary count endpoint described for this trial.
What does over-dispersion mean in general?
General: over-dispersion occurs when the variability in count data is greater than expected under a simple statistical model, often because observations differ in their underlying event rates or are more variable than the model assumes. A model that ignores over-dispersion may understate uncertainty. This trial’s primary outcome is reported as participants with symptoms, not as a recurrent-event count model, and the registry does not report a model for over-dispersion. The concept therefore provides general statistical context rather than a claim about the analysis used in this study.
What can be inferred from the listed analyses?
The registry record lists 13 outcome measures and no analysis entries. It does not report the inferential methods, adjustment strategy, or analysis populations for the secondary outcomes. Without those details, readers cannot establish whether any formal comparisons were planned or how uncertainty was to be quantified. The sound interpretation is limited to the outcome definitions and descriptive safety counts actually reported, with unreported analysis details identified as not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures, including local reactogenicity as the primary outcome and CD4 cell counts, viral load, and serum VRC07 antibody concentration among secondary outcomes. When a study assesses multiple outcomes, the chance of at least one apparently unusual finding can increase if each outcome is tested separately. General: statistical methods for addressing multiplicity can include designating a primary outcome, adjusting significance thresholds, or interpreting secondary results as exploratory. The registry record does not report a multiplicity strategy or a statistical analysis plan. It therefore does not establish whether any adjustment was planned for the listed outcomes.
The primary outcome population included enrolled participants who received AAV8-VRC07 and provided safety data through a diary card. This definition differs from simply including everyone enrolled: receipt of product and availability of safety data are stated requirements. The registry record does not report how many participants lacked diary data, whether any diaries were incomplete, or how missing symptom reports were handled. It also does not report imputation methods or sensitivity analyses for missing safety information.
The registry record does not describe analysis populations for the secondary outcomes, such as whether each outcome used the same participants or a different set according to data availability. Nor does it report the number analyzed for those outcomes. The record lists no analysis entries for the outcomes in the information available. Consequently, it is not possible to assess how missingness, participant exclusions, or multiplicity may have affected any inferential results. These matters are not reported in the registry record.
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 |
|---|---|---|---|
| Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | 0 | 3 | 0.0% |
| Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | 1 | 3 | 33.3% |
| Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | 0 of 3 |
| Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | 1 of 3 |
| Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) | 0 of 4 |
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 |
|---|---|
| Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | 2 of 3 |
| Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | 2 of 3 |
| Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) |
|---|---|---|---|---|
| Overdose | Injury, poisoning and procedural complications | 0 of 3 | 1 of 3 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: AAV8-VRC07 (5 x 10^10 vg/kg IM) | Group 2: AAV8-VRC07 (5 x 10^11 vg/kg IM) | Group 3: AAV8-VRC07 (2.5 x 10^12 vg/kg IM) |
|---|---|---|---|---|
| Administration site pain | General disorders | 0 of 3 | 0 of 3 | 4 of 4 |
| Blood creatinine increased | Investigations | 1 of 3 | 0 of 3 | 2 of 4 |
| Aspartate aminotransferase increased | Investigations | 2 of 3 | 0 of 3 | 0 of 4 |
| Myalgia | Musculoskeletal and connective tissue disorders | 0 of 3 | 1 of 3 | 1 of 4 |
| Headache | Nervous system disorders | 0 of 3 | 0 of 3 | 2 of 4 |
| Diarrhoea | Gastrointestinal disorders | 1 of 3 | 0 of 3 | 0 of 4 |
| Upper respiratory tract infection | Infections and infestations | 0 of 3 | 1 of 3 | 0 of 4 |
| Diabetes mellitus | Metabolism and nutrition disorders | 0 of 3 | 1 of 3 | 0 of 4 |
Serious events with the highest arm-level rate: overdose (33.3%).
The registry reports serious adverse event counts by dose group: Group 1 has 0 serious events among 3 at risk, Group 2 has 1 among 3, and Group 3 has 0 among 4. The listed counts for other adverse events are 2 among 3, 2 among 3, and 4 among 4, respectively. The record also lists 1 death in Group 2 and 0 in each of the other groups.
These are descriptive registry counts, not estimates from a randomized comparison. The non-randomized design means that the groups should not be treated as equivalent control arms. The counts do not establish that a dose caused an event or that a difference between groups is attributable to dose. The registry record does not report the cause of the death or its relationship to the study product.
Overdose is listed as a top serious event term with 33.3%. The available information does not establish the context or denominator for that percentage, so it should not be interpreted as a participant-level risk. Serious-event counts, other-event counts, and the primary local reactogenicity endpoint are distinct measures; the registry record does not report the primary symptom results.
12. What the Result Does, and Does Not, Mean
The record describes a small Phase 1 dose-escalation safety study and identifies the primary question as whether participants reported local reactogenicity during the 7 days after AAV8-VRC07 administration. It also provides serious and other adverse event counts by dose group. Those counts give descriptive information about events recorded in the study, but the design does not support treating the groups as randomized comparators.
The primary local symptom counts and severity results are not reported in the registry information. Therefore, readers cannot use this record to quantify the frequency or severity of local reactogenicity. The listed serious and other adverse event counts do not substitute for that endpoint, because they represent different safety summaries. The registry also does not report the clinical context or product attribution for the listed death.
The trial’s objectives included assessing whether cells produced VRC07 antibody, and the registry lists antibody concentration, CD4 cell counts, and viral load as secondary outcomes. The record does not report results for those outcomes in the information. It therefore cannot establish the extent of antibody production or describe changes in those clinical measures.
General: in an early-phase, non-randomized study, observed counts can help characterize what was recorded in the study population, but they do not by themselves establish comparative benefit, causal safety effects, or how outcomes would occur in a broader population. Precision depends on the amount and completeness of information, as well as on the statistical method. The registry record does not provide comparative estimates or confidence intervals for the listed safety outcomes.
The appropriate reading is limited: the registry describes the study design, endpoint definitions, and event counts, while leaving important primary results and analysis details unreported. These limitations mean the posted information is not a basis for a treatment-effect conclusion.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how early-phase dose-escalation studies differ from randomized efficacy comparisons. Its non-randomized, unmasked, parallel-group design focuses on safety and tolerability across dose groups. The distinction matters because descriptive group counts can identify what was recorded, but cannot isolate a dose effect in the way a randomized comparison is intended to do.
The primary endpoint also illustrates why outcome definitions must be read closely. Participants were counted once per symptom at the worst severity reported during the 7-day diary period, while the “Any Local Symptom” outcome summarizes participants reporting any local symptom. These are related but not identical summaries. Clear definitions help prevent readers from confusing repeated symptom reports, symptom-specific counts, and participants with any symptom.
The record makes another important statistical point: an outcome definition is not a result. Although the primary endpoint is described, its observed counts and severity findings are not reported in the registry information. Likewise, the listed secondary outcomes do not have results reported in that information. This limits the conclusions that can be drawn, regardless of how clearly the endpoint itself is specified.
Finally, the serious and other adverse event counts should be kept in context. The groups are not randomized control arms, the record does not provide inferential comparisons, and attribution details are not reported for the death. The case shows why registry readers should distinguish descriptive safety information from evidence of causation or comparative treatment effects, and why missing analysis and reporting details affect interpretation.
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 available registry information has several trial-specific limitations. The primary outcome is defined in detail, including its 7-day timeframe, diary-card collection, worst-severity rule, and grading source, but the symptom counts and severity results are not reported. This prevents direct assessment of the primary endpoint’s observed frequency.
The study is non-randomized and has no masking. The three dose groups therefore should not be read as controlled comparisons. The registry record does not report a statistical analysis plan, an adjusted comparison, or a rationale for allocation. It also does not report the trial’s sample-size justification. The planning assumptions described in the sample-size material are illustrations and should not be treated as the study’s design justification or as observed power.
The registry lists serious and other adverse event counts and a death by group, but does not report the death’s cause or relationship to study product in the information. It lists Overdose as a top serious event term with 33.3%, but the available information does not establish the context needed to interpret that percentage as a group-specific risk. The primary local reactogenicity outcome is separate from these event summaries.
For the primary endpoint, the safety population required receipt of product and diary-card data. The registry record does not report missing diary information, completeness of follow-up, or how missing outcomes were handled. It also does not report analysis populations or results for the secondary outcomes. These omissions limit assessment of precision, completeness, and the extent to which the posted counts represent the intended study population.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Tolerability of AAV8 Delivery of a Broadly Neutralizing Antibody in Adults Living With HIV: a Phase 1, Dose-escalation Trial — NCT03374202.
- Registry record last updated 2026-10-27; status last verified 2026-10.
- Results first posted 2023-10-25.
- 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
NCT03374202 is a completed Phase 1, non-randomized, unmasked, parallel-group dose-escalation study of AAV8-VRC07 in adults with controlled HIV-1 infection receiving antiretroviral treatment. The registry lists enrollment of 10 and three intramuscular dose groups. The primary outcome counts participants reporting local reactogenicity during the 7 days after administration, with diary-card reporting and severity grading described in the record.
The registry lists serious and other adverse event counts by group, including 1 death in Group 2, but does not report the cause or product relationship of that death in the information. The primary local symptom results and secondary outcome results are not reported in that information. The registry record also does not report an analysis plan, missing-data methods, or multiplicity strategy. Interpretation is consequently limited to the study design, outcome definitions, and descriptive safety counts.