Combination Therapy With VRC01 and 10-1074 in HIV-Infected Individuals Undergoing Sequential Treatment Interruptions: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Therapy With VRC01 and 10-1074 in HIV-Infected Individuals Undergoing Sequential Treatment Interruptions (NCT03831945), a randomized phase 1 study. The primary outcome is Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART.

2. Clinical Question

The registry record concerns whether a single infusion of VRC01 and 10-1074 could be studied for safety and HIV control during periods when participants were not taking antiretroviral therapy (ART). The primary outcome focuses on the second analytical treatment interruption (ATI): the time from its start until a participant met criteria to restart ART, assessed for up to 16 weeks. This is a time-to-event question, where the event is reaching a restart criterion.

3. Trial Design

This was a phase 1 study of VRC01 and 10-1074 in people with HIV undergoing sequential treatment interruptions. The record lists randomized allocation and double masking, but also labels the model as single-group. It names an infusion of VRC01 and 10-1074 and an infusion of normal saline; how the single-group model label relates to the randomized, two-arm descriptions is not reported in the registry record. Enrollment was 27. The study status is terminated.

The summary describes screening, an initial interruption of HIV medicines, an infusion phase, and a later interruption after HIV levels became undetectable for 3 months. In the treatment phase, the study drugs or saline placebo were administered intravenously when viral load reached the stated threshold of >= 200 copies/mL. Participants were also described as restarting HIV medicines after the infusion phase and later stopping them again for the second interruption. The primary outcome pertains to this second ATI, not the first one.

The registry lists a start date of 2019-04-04 and a primary completion date of 2020-12-08. It states that safety concerns about stopping HIV treatment during the COVID-19 pandemic led to the study being halted before sufficient participants had completed the relevant phase. The summary does not give further details about the stopping decision or its timing.

These design features matter for interpretation. A randomized, masked comparison can support a between-arm assessment when enough relevant outcome data and an analysis are available. Here, the posted primary results are small arm-specific summaries among participants who completed the second ATI. The registry record does not provide a formal comparative analysis, and the termination context limits the amount of primary endpoint information available.

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: 27 subjects were consented to protocol. 20 subjects started the study. Five subjects enrolled but not randomized due to the coronavirus disease 2019 (COVID 19) pandemic; one subject was lost to follow-up after enrollment, and one subjects not randomized due to hospitalization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analyses included all subjects who completed the second analytical treatment interruption phase. Because of safety concerns that stopping treatment for HIV during the current COVID-19 pandemic could increase the risk of getting severe COVID-19, the study was halted before sufficient participants had enrolled and completed the second analytical treatment interruption to accurately determine primary outcome

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 Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART, measured over From start of second Analytical Treatment Interruption (ATI) until up to 16 weeks.

The primary endpoint is the number of days from the start of the second analytical treatment interruption until a participant met criteria to restart antiretroviral therapy (ART), with assessment described as lasting up to 16 weeks. The reported statistic is the median, with an inter-quartile range (IQR). The event is reaching a restart criterion, rather than simply completing the interruption or receiving an infusion.

The listed criteria include a confirmed >30% decline in baseline CD4+ T cell count, or an absolute CD4+ T cell count in the setting of detectable HIV viremia (>40 copies/mL); a sustained (>4weeks) HIV RNA level of > 1000 copies/mL; or HIV-related symptoms or pregnancy. These are the registry’s stated criteria, and the record does not further explain their application or how simultaneous criteria were handled.

A time-to-event endpoint is useful when the timing of an event is important and participants may reach it at different times. A median gives the middle of the observed event-time distribution; the IQR describes the middle half of the reported values. These summaries do not, by themselves, estimate a treatment effect or establish how precisely the arms differ. The registry reports medians of 57.0 days and 63.0 days, with IQRs of 50.5 to 59.0 and 51.25 to 78.5, respectively. It does not report a confidence interval for either median or a comparative hazard ratio.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a time-to-event measure: time begins at the start of the second ATI, and the event is meeting a criterion to restart ART. The registry reports a median time for each arm and an IQR. It does not report a hazard ratio or another comparative estimate for this endpoint. The explanations below describe general statistical concepts; they should not be taken as a description of methods that the study used unless the registry record says so.

What does a median time describe?

Generally, the median is the point at which half of the observed times fall at or below it and half fall at or above it. It provides a central summary that is less affected by unusually long or short values than an arithmetic mean can be. In this record, the median is 57.0 days for the VRC01 and 10-1074 arm and 63.0 days for the saline arm. These are arm-specific summaries, not a direct estimate of the effect of assignment to one arm rather than the other.

The IQR gives the interval between the first and third quartiles, describing the middle half of the observed values. The reported IQR is 50.5 to 59.0 for the VRC01 and 10-1074 arm, and 51.25 to 78.5 for the saline arm. It is a measure of spread in the data, not a confidence interval. An IQR does not show how precisely the median has been estimated, nor does it test whether the arms differ.

Why are time-to-event methods relevant?

In general, time-to-event methods are useful when the outcome is the time until an event and not every participant is observed to experience that event during the study period. Some participants may leave observation or reach the end of follow-up without the event. Such observations can be censored, meaning that the exact event time is not known, but the available follow-up still contributes information. A Kaplan-Meier curve is one common way to display event-free probability over time, and a hazard ratio is one possible comparative summary. The registry record does not report a hazard ratio, a Kaplan-Meier estimate, or details about censoring for this endpoint. It would be inappropriate to assume that any particular method was used.

When data are sparse, the distribution of event times and the way incomplete follow-up is handled can strongly affect a summary. Here, only participants who completed the second ATI are included in the stated primary analysis population, and the endpoint counts are 3 and 4. The record does not report the individual time values or explain whether anyone in that population was censored before meeting a restart criterion.

What can a confidence interval add?

Generally, a confidence interval describes uncertainty around an estimated quantity under a specified statistical model and procedure. An interval for each arm’s median would describe uncertainty in those separate summaries. An interval for a treatment contrast would address uncertainty in the comparison itself. These answer different questions: overlapping or non-overlapping intervals for separate arm estimates are not a substitute for a formal comparison. No confidence intervals for the medians or for a between-arm effect are reported in the registry record.

Small analysis groups typically produce limited information and can yield imprecise estimates. The medians and IQRs should therefore be read as descriptions of the observed participants, rather than stable estimates of what would be expected in a larger population. The record does not report a precision target or a statistical test for this endpoint.

Why can over-dispersion matter?

Generally, over-dispersion means that observed variability is greater than a statistical model expects. It can make standard errors that rely on a simple model too small, leading to intervals that are too narrow or tests that appear more decisive than warranted. This issue is especially relevant for some count outcomes and clustered data. The primary outcome is a time-to-event measure, and the registry record does not report an over-dispersion assessment or a model for the endpoint. It is therefore a general caution, not a claim about a specific analysis in this study.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, it says planning tables give a total number of events. These are planning assumptions, not evidence of the study’s original sample-size justification, and the registry record does not report that justification. A planning illustration is not observed power and does not change the descriptive nature of the posted endpoint results.

The record lists zero analyses for the primary outcome and notes that a two-arm comparison was not estimable. As a result, the methods that would underlie a comparative treatment estimate cannot be evaluated from the posted information. The arm-level median and IQR remain interpretable as descriptive statistics, with substantial caution because of the limited analysis counts and the analysis-population restriction.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome: the percent of participants with grade 3 or higher related adverse events. The primary endpoint concerns time to meeting criteria to restart ART during the second ATI. The record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a plan for controlling the chance of false-positive findings across outcomes. Without such information, the posted results should not be treated as a set of confirmatory tests.

The registry reports zero analyses for the primary endpoint and says values were missing or not estimable for a two-arm comparison of the median-time outcome. It does provide separate medians and IQRs for the arm-specific analysis groups. It does not report a formal comparative test, a confidence interval, or a hazard ratio for this outcome.

The stated primary analysis included all subjects who completed the second ATI. This definition makes completion of that phase a condition for inclusion; the record does not describe how participants who did not complete it were handled in analyses, or how missing endpoint information was treated. It does not report an imputation method, sensitivity analysis, or reasons for missing primary outcome data beyond the study being halted before sufficient participants completed the phase. The record does not clarify whether or how the outcome analysis population relates to all randomized participants.

These limitations are important because the analyzed group is small and selected by completion of the second interruption. The result can describe the reported participants, but the registry record does not establish that it represents all enrolled participants or the population the study intended to examine.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (10.0%), cholelithiasis (10.0%).

The adverse-event record reports serious related adverse events for 2 participants in the VRC01 and 10-1074 group and 0 in the normal saline group. It lists 10 participants at risk for this measure in each group. It also reports other adverse events affecting 9 participants in the VRC01 and 10-1074 group and 10 in the saline group, with 10 at risk in each group. Deaths are reported as 0 in both groups.

The registry lists atrial fibrillation and cholelithiasis among the top serious-event terms, each at 10.0%. The record does not identify which arm these terms occurred in or establish that either was caused by study treatment. An adverse event occurring during a study is not, by that fact alone, evidence of causation. The counts also do not show the severity, timing, duration, or clinical course of each event.

The secondary outcome is described as the percent of participants with grade 3 or higher related adverse events, but the adverse-event summary contains counts rather than a comparative statistical analysis. Small groups and brief exposure can make uncommon events difficult to characterize. These data support a descriptive account of reported events; they do not establish comparative safety or rule out risks not observed in the study.

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

The posted primary outcome results describe how long the included participants took to meet criteria for restarting ART during the second treatment interruption. The median was 57.0 days for the VRC01 and 10-1074 arm and 63.0 days for the normal saline arm. Their IQRs were 50.5 to 59.0 and 51.25 to 78.5, respectively. These summaries apply to the participants who completed the second ATI and were included in the primary analysis, whose arm counts were 3 and 4.

Those data do not establish that the study infusion caused a change in time to meeting restart criteria. The registry record does not report a comparative estimate, confidence interval, hazard ratio, or statistical test for the primary outcome. It also reports that a two-arm comparison was not estimable. The medians should not be interpreted as proof of a difference or proof that the arms are equivalent.

The results do not describe the experience of all 27 enrolled participants: the primary analysis population is specifically defined by completion of the second ATI, and its reported counts are smaller. The record says the study was halted before sufficient participants had completed that phase because of safety concerns about treatment interruption during the COVID-19 pandemic. It does not report how many participants discontinued or how incomplete endpoint data were handled.

The adverse-event counts are also descriptive. The serious related-event counts were 2 and 0, with 10 at risk in each arm, and deaths were 0 in each arm. These observations do not determine whether events were caused by treatment or provide a precise comparison of safety. The record supports a limited account of observed outcomes in a small completion-defined analysis group, not a definitive conclusion about comparative benefit or harm.

13. Why This Trial Matters Statistically

This trial illustrates why a trial’s status, analysis population, and estimand matter alongside the endpoint values. Enrollment was 27, but the primary outcome analysis included only participants who completed the second ATI. The arm-specific endpoint counts were 3 and 4. A reader who focuses only on the overall enrollment figure could mistake the reported medians for estimates based on everyone enrolled.

It also shows the distinction between descriptive results and comparative inference. Medians and IQRs can summarize the observed event times in each arm, but they do not by themselves quantify an intervention contrast. The registry record reports no formal comparative estimate for the primary endpoint and states that a two-arm comparison was not estimable. A numerical difference between arm summaries is not a substitute for an uncertainty estimate or a specified comparison.

The termination context is statistically important, too. The study was halted before sufficient participants had completed the second ATI because of safety concerns about treatment interruption during the COVID-19 pandemic. Termination can leave planned analyses with limited outcome information, but the record does not report the original statistical plan or how the halt affected each analysis. Those details cannot be reconstructed from the posted results.

Finally, this record is a reminder that safety summaries and time-to-event endpoints answer different questions. Counts of adverse events describe reported safety observations, while the primary endpoint describes time until a restart criterion was met. Neither set of summaries supports conclusions beyond the participants and information actually reported. The value of the record is its transparent description of a limited dataset and its constraints, not a definitive comparative estimate.

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 is the small primary endpoint analysis group: the registry reports 3 participants in the VRC01 and 10-1074 arm and 4 in the normal saline arm. The primary analysis included subjects who completed the second ATI, so it does not cover everyone enrolled. How this completion-defined population relates to the randomized population is not reported in the registry record.

The trial was terminated, and the record says it was halted before sufficient participants completed the relevant phase because of safety concerns about stopping HIV treatment during the COVID-19 pandemic. The registry does not report the original sample-size justification, interim analyses, or a statistical plan, nor does it detail how termination affected data collection and follow-up.

The posted primary results are arm-specific medians and IQRs, without a formal comparative estimate. The registry notes that a two-arm comparison was not estimable. It does not report participant-level event times, confidence intervals, a hazard ratio, or details about censoring. This limits assessment of both the precision of the medians and the comparison between arms.

Missing-data methods are not reported. In particular, the record does not describe how people who did not complete the second ATI, or any missing time-to-event information, were handled. The registry’s design labels also include randomized allocation and double masking alongside a single-group model; the relationship among those descriptions is not explained.

Finally, the adverse-event figures are small descriptive counts. The record does not provide enough detail to infer causation or to characterize uncommon risks with precision. The conclusions that can be drawn are therefore restricted to the reported outcomes and participants.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combination Therapy With VRC01 and 10-1074 in HIV-Infected Individuals Undergoing Sequential Treatment Interruptions — NCT03831945.
• Registry record last updated 2021-10-12; status last verified 2021-08.
• Results first posted 2021-10-12.
• 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.

18. Record Summary

The registry record describes NCT03831945, a phase 1 study of VRC01 and 10-1074 in people with HIV undergoing sequential treatment interruptions. It lists randomized allocation and double masking, while also classifying the model as single-group. Enrollment was 27, and the study status is terminated. The record gives a start date of 2019-04-04 and a primary completion date of 2020-12-08.

The primary outcome is time from the start of the second ATI to meeting criteria to restart ART, assessed up to 16 weeks. Reported medians are 57.0 days for VRC01 and 10-1074 and 63.0 days for normal saline; the respective analysis counts are 3 and 4. A formal two-arm comparison is not reported and is described as not estimable.

The record states that the study was halted before sufficient participants completed the second ATI because of safety concerns about treatment interruption during the COVID-19 pandemic. Adverse-event summaries include serious related events in 2 participants in the VRC01 and 10-1074 group and 0 in the saline group, with 10 at risk in each group. The results are descriptive and do not establish comparative efficacy or safety.