Lamivudine/Dolutegravir in Virologically Suppressed Subjects With Expected or Confirmed Resistance to Lamivudine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lamivudine/Dolutegravir in Virologically Suppressed Subjects With Expected or Confirmed Resistance to Lamivudine (NCT04880785), a na phase 2 study. The primary outcome is The Efficacy of a Switch to DTG/3TC for Maintenance of Virologic Suppression, in Persons With Past Confirmed or Suspected 3TC Resistance, When Proviral DNA Population Sequencing Does Not Detect 3TC Resistance-associated Mutations at Baseline..

2. Clinical Question

The trial addresses a focused question about a treatment switch in people whose virus was suppressed but whose treatment history raised concern about lamivudine resistance. The registry description distinguishes past or suspected resistance from mutations detected by proviral DNA population sequencing at baseline. Its stated hypothesis also concerns archived minority resistance-associated mutations detected by next-generation sequencing, and whether those mutations would affect efficacy. That hypothesis is not itself a reported finding.

The study enrolled 167 participants and was described as phase IIa, open-label, single-arm, and multicentric. Because there was no concurrent comparator, the primary question is about outcomes observed in the treated group, not a randomized estimate of the difference between two regimens. The record does not report a primary endpoint estimate that would answer how often suppression was maintained in the defined population.

Several secondary outcomes broadened the questions, including virologic control, viral resistance in participants experiencing virologic failure, time to virologic failure, and subgroup outcomes by resistance history and prior integrase inhibitor exposure. Other listed outcomes concern time on lamivudine or emtricitabine and baseline resistance-associated mutations detected by next-generation sequencing at specified thresholds. These are additional questions; they do not replace the primary Week 48 question.

3. Trial Design

The registry record describes a phase II study of dolutegravir plus lamivudine in people with HIV infection. The brief description calls it a phase IIa, open-label, single-arm, multicentric study. The recorded allocation is not applicable, the masking is none, and the study model is single group. It was completed, with enrollment of 167 participants.

Participants received dolutegravir 50 mg and lamivudine 300 mg as one film-coated tablet once daily during 96 weeks. The registry identifies the drug as Dovato. The primary outcome timeframe was Week 48, so the primary question concerns a time point within the stated treatment period. The registry record does not report the full visit schedule or the details of how outcomes were assessed at every visit.

In a single-group study, each participant receives the study intervention, and the observed outcomes describe that group. Without a concurrent control group, the design does not directly estimate how outcomes would have differed under another treatment assignment. Open-label status means masking was not used; the registry record does not report further procedures to reduce potential assessment or reporting effects.

The record lists HIV infections as the condition and Fundacion SEIMC-GESIDA as the sponsor. The recorded study start was 2021-07-28, and primary completion was 2023-06-12. The study status is completed. These design and conduct details establish the context for reading the outcomes, but they do not establish the study’s efficacy result or explain its planning rationale.

The registry record does not report a sample-size justification, a formal statistical analysis plan, or interim analyses. It also does not report a randomized comparison. Those omissions matter when interpreting the scope of conclusions: the study describes outcomes after a switch in the enrolled group, but the record does not establish a prespecified framework for estimating comparative treatment effects.

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: Between 28 July 2021 and 11 April 2022, 167 individuals were enrolled (signed the informed consent): 46 were screening failures and 121 were included (all received ≥1 dose of Dolutegravir/lamivudine \[DTG/3TC\] and constitute the ITT-e population). Twelve participants discontinued before week 48 and a further four between weeks 48 and 96, leaving 105 (86.8 %) on study at week 96.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 4 participants in HIV-1 RNA ≥50 copies/mL category: 0 HIV-1 RNA ≥50 copies/mL in W48 window; 2 Discontinuation due to Lack of Efficacy (1 Confirmed Virologic Withdrawal \[CVW\]/ 1 Precautionary Virologic Withdrawal \[PVW\]) and 2 Discontinuation for other reasons and Last available HIV-1 RNA ≥50 copies/mL. 8 participants in No virologic data at week 48: 3 Discontinuation Due to an Adverse Event and 5 Discontinuation for other reasons and Last available HIV-1 RNA \<50 copies/mL.

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 The Efficacy of a Switch to DTG/3TC for Maintenance of Virologic Suppression, in Persons With Past Confirmed or Suspected 3TC Resistance, When Proviral DNA Population Sequencing Does Not Detect 3TC Resistance-associated Mutations at Baseline., measured over Week 48.

The primary endpoint concerns the efficacy of switching to dolutegravir plus lamivudine for maintaining virologic suppression in people with past confirmed or suspected lamivudine resistance, when baseline proviral DNA population sequencing did not detect lamivudine resistance-associated mutations. Its timeframe is Week 48, and the outcome is expressed as a count of participants.

Virologic suppression is central to the stated research question because the study enrolled people described as suppressed before the switch and asked whether suppression could be maintained afterward. A count can communicate how many participants fall into a specified outcome category, but its interpretation depends on the category definition and the denominator used. The registry description includes a category for HIV-1 RNA at least 50 copies/mL and says that participants who discontinued with their last available HIV-1 RNA at least 50 copies/mL were to be reported in that category at Week 48.

The record describes four participants in the HIV-1 RNA at least 50 copies/mL category: zero with HIV-1 RNA at least 50 copies/mL in the Week 48 window, two discontinuations due to lack of efficacy, and two discontinuations for other reasons with a last available HIV-1 RNA at least 50 copies/mL. The record also reports eight participants with no data at Week 48. These statements describe how the registry classified outcomes; they do not provide a complete endpoint estimate or the corresponding denominator for a success proportion.

The endpoint is therefore informative about the study’s intended clinical question, but the posted record does not report enough detail to derive a complete Week 48 response estimate or its precision. The protocol definition beyond the registry description is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a participant-count outcome at Week 48. A count records how many participants meet a defined outcome category. General statistical explanation: a count is easiest to interpret when its category definition, analysis population, and denominator are clear. A count alone does not show the uncertainty around an estimate or how the result might compare with another treatment.

What does a single-group design estimate?

The study is recorded as single group, with no allocation to a separate comparator. General statistical explanation: a single-group study can describe outcomes among people receiving an intervention, but it does not directly estimate a treatment contrast against a concurrent control. A treatment contrast requires outcomes under distinct treatment conditions and a defined comparison. In a single-group design, the observed outcome cannot by itself show what would have happened to those same participants under another treatment.

The study is also open-label, with masking recorded as none. General statistical explanation: masking can reduce the influence of treatment knowledge on some aspects of care, reporting, or assessment, depending on the outcome and study procedures. The registry record does not report additional masking or blinded assessment procedures. The endpoint includes a laboratory threshold, but the record does not describe laboratory procedures or assessment safeguards beyond the endpoint language.

How should a threshold-based outcome be read?

The endpoint description uses HIV-1 RNA at least 50 copies/mL as a category and specifies how some discontinuations were classified. General statistical explanation: a threshold turns a continuous measurement into categories. That can make an outcome straightforward to count, but it also means interpretation depends on the threshold and the timing of the measurement. A value at a scheduled visit and a last available value after discontinuation are not necessarily observations from the same time point. The registry explicitly says that discontinuers with a last available value meeting the threshold were to be placed in the relevant Week 48 category.

The record reports zero participants with HIV-1 RNA at least 50 copies/mL in the Week 48 window, alongside discontinuation categories based on last available measurements. Those statements should not be collapsed into a single unqualified statement about all participants at Week 48. The description does not provide a complete account of every participant’s endpoint status or a full denominator for a response estimate.

What does a confidence interval contribute?

General statistical explanation: a confidence interval expresses the uncertainty around an estimated quantity under a statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, while neither width nor position alone resolves questions about study design, bias, or clinical importance. No confidence interval for the primary Week 48 outcome is reported in the registry record. Consequently, the precision of a primary outcome estimate cannot be evaluated from the posted results.

A p-value, when reported, addresses how compatible data are with a specified statistical model and null hypothesis. It is not a measure of effect size, does not indicate the probability that a hypothesis is true, and does not replace an estimate with its uncertainty. The registry record does not report a primary p-value or the statistical test used for the primary outcome.

How do subgroup and secondary outcomes fit?

The registry lists secondary questions about virologic control, resistance among participants experiencing virologic failure, time to virologic failure, and outcomes in subgroups defined by resistance history, prior integrase inhibitor exposure, and time on lamivudine or emtricitabine. It also lists baseline resistance-associated mutations detected by next-generation sequencing at 1, 5, and 20% thresholds. These outcomes address distinct questions and may use different outcome definitions or analysis populations. Their results are not reported in the registry record.

General statistical explanation: when a study assesses multiple outcomes or subgroups, the chance of finding an apparently notable result among them can increase if no approach to multiplicity is specified. The registry record does not report a multiplicity strategy or a statistical analysis plan. It is therefore not possible to determine from the record whether or how the investigators adjusted interpretation for multiple testing.

What is the role of planning illustrations?

The record describes sample-size illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It distinguishes illustrations for participants per arm for 80% power and other planning levels from time-to-event illustrations expressed as total events. These are planning illustrations, not the trial’s own sample-size justification, and they are not observed power. The actual study is single-group, so hypothetical equal allocation between two arms does not describe its design. The registry record does not report the trial’s sample-size justification.

General statistical explanation: power is a design-stage quantity that depends on assumptions about the effect to detect, variability, analysis method, and design. It does not describe the probability that a particular observed result is true. A sample-size calculation also cannot compensate for missing outcome data or the absence of a comparator. The assumptions in a planning exercise should therefore be kept separate from the evidence generated by the enrolled study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including virologic control, viral resistance among participants experiencing virologic failure, time to virologic failure, and several subgroup questions. It also lists outcomes concerning time virologically suppressed and baseline resistance-associated mutations detected by next-generation sequencing at 1, 5, and 20% thresholds. The record lists 16 outcome measures and no analyses. A statistical plan for handling multiple outcomes or subgroup comparisons is not reported in the registry record.

General statistical explanation: when many outcomes or subgroups are examined, interpreting each result as if it were the only planned analysis can overstate the strength of evidence. A prespecified hierarchy or multiplicity adjustment can help manage that issue, but the registry record does not report whether such methods were used. No outcome-specific estimates are reported for the secondary questions, so their results cannot be evaluated.

The primary outcome description states that eight participants had no data at Week 48. The reasons listed are one loss to follow-up, one protocol deviation involving M184V at screening, two investigator decisions—one for lung cancer and one after M184V was detected in plasma RNA population genotyping at transient rebound—one consent withdrawal, and three withdrawals for adverse events. The record says the participant with M184V detected at transient rebound was suppressed with dolutegravir/lamivudine and did not fulfil criteria for virologic withdrawal.

The record also says it was prespecified to report participants who discontinued with a last available HIV-1 RNA at least 50 copies/mL in that category at Week 48. General statistical explanation: missing-data handling can influence an endpoint estimate, especially when reasons for missingness may relate to outcomes. The registry description does not report a complete analysis population, a formal missing-data method, or sensitivity analyses. It is therefore not possible to assess how alternative handling of missing Week 48 outcomes would affect the estimate.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: proliferative cystitis (0.6%), nephritic colic (0.6%), fracture of the left oleacron (0.6%), cutaneous abscess (0.6%), lung adenocarcinoma lsd and t4 n2 m1c (0.6%).

For the Dovato group, the registry reports 167 participants at risk for serious adverse events and 17 participants affected. It reports 167 participants at risk for other adverse events and 65 affected. One death is recorded. The registry record does not state in this summary whether the death was related to treatment, nor does it establish a causal relationship between the treatment and any reported event.

The listed serious adverse event terms include proliferative cystitis, nephritic colic, fracture of the left oleacron, cutaneous abscess, lung adenocarcinoma LSD and T4 N2 M1c, and depression. Each is displayed as 0.6%. These figures describe the registry’s listed serious-event terms; they should not be treated as a complete account of every safety outcome or as estimates of comparative risk.

General statistical explanation: safety counts are easier to interpret when the event definition, observation period, and whether counts refer to participants or events are clear. The registry reports participants affected and a participant-at-risk count for the groups shown, but this summary does not provide event timing, exposure-adjusted rates, or a comparator group. A single-group safety count can describe what was reported during the study, but cannot by itself determine whether an event was caused by treatment or whether its frequency differs from another regimen.

The record does not report further detail about event severity beyond the serious-event designation, duration, management, or causal assessment. The serious-event figures should therefore be read as descriptive registry counts with the limits of the reported information.

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

The study’s design and endpoint address a specific question: whether virologic suppression was maintained at Week 48 after a switch to dolutegravir plus lamivudine in people with past or suspected lamivudine resistance who did not have resistance-associated mutations detected by baseline proviral DNA population sequencing. The record identifies the treatment, population, timeframe, and some outcome-classification rules.

It does not report a complete primary efficacy estimate, its denominator, or an interval describing its precision. Although the endpoint description gives details for participants placed in the HIV-1 RNA at least 50 copies/mL category and notes eight participants without Week 48 data, those details do not provide a complete account of the primary outcome. The registry record therefore does not establish the overall frequency of maintained suppression or the uncertainty around that frequency.

The study is single-group and open-label, with no concurrent comparator. Its observations cannot be read as a randomized estimate of how the regimen compares with another treatment. The registry record also does not report a statistical analysis plan, a sample-size justification, interim analyses, or a reported primary hypothesis test. Without those details and a complete endpoint estimate, statistical significance and precision cannot be assessed.

The stated hypothesis about minority resistance-associated mutations is a research question, not a reported result. The listed secondary outcomes describe questions about virologic failure, resistance, time to events, subgroups, and sequencing thresholds, but their results are not reported in the registry record. The posted information supports a description of the trial’s design and outcome-classification details, not a conclusion that the regimen did or did not maintain suppression, nor a comparative claim about treatment effects.

13. Why This Trial Matters Statistically

This trial is statistically informative because it focuses on a population defined by both treatment history and resistance testing. The registry distinguishes past confirmed or suspected lamivudine resistance from mutations detected by proviral DNA population sequencing at baseline. It also states a hypothesis concerning archived minority mutations identified by next-generation sequencing. This makes clear that resistance characterization and assay approach are central to the research question.

The design also illustrates why the form of a study matters as much as the endpoint. A single-group study can describe outcomes after a treatment switch, but it does not create a concurrent comparison with another regimen. That distinction limits the kinds of treatment-effect claims that can be made from the design, independent of how carefully outcomes are counted.

The Week 48 endpoint description highlights another important issue: outcome classification can incorporate information from participants who discontinue, including last available measurements. That approach may preserve clinically relevant information, but interpretation depends on the prespecified category rules and on transparent reporting of denominators and missing data. The record reports some of those rules and the reasons for missing Week 48 data, yet does not report a complete primary outcome estimate.

The listed secondary questions also show the complexity of studying virologic outcomes across resistance histories, prior treatment exposures, and sequencing thresholds. Each additional question can be useful, but interpretation depends on clear definitions, adequate information, and a reported plan for multiple analyses. The registry record does not provide those results or the statistical plan. The trial therefore matters as an example of a focused and technically specific clinical question for which the registry design and classification details are available, while the reported statistical evidence remains incomplete.

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 principal limitation for interpreting this trial from the registry record is that the primary Week 48 outcome is not reported as a complete estimate with a clear denominator and measure of precision. The record gives some classification details, but does not report a complete count or proportion of participants maintaining suppression. A confidence interval and primary p-value are not reported in the registry record.

The single-group, open-label design has no concurrent comparator. Outcomes in the treated group therefore cannot establish a comparative treatment effect. The record also does not report a formal statistical analysis plan, sample-size justification, interim analyses, or an analysis population definition. The listed planning illustrations are not a substitute for the study’s own design justification.

Week 48 data were unavailable for eight participants, and the record lists several different reasons. The outcome description also combines a scheduled Week 48 window with classification based on last available HIV-1 RNA for certain discontinuations. The record does not report a full missing-data analysis or sensitivity analyses to show how alternative handling might affect the endpoint estimate.

The treatment period is described as 96 weeks, while the primary outcome timeframe is Week 48. The registry lists secondary outcomes extending to other virologic and resistance questions, but their results are not reported in the registry record. The record does not provide enough information to evaluate the precision or multiplicity of those additional analyses.

Finally, the population and resistance question are specific: the primary question concerns people with past confirmed or suspected resistance whose baseline proviral DNA population sequencing did not detect resistance-associated mutations. The registry record does not provide further details on how broadly the enrolled participants represent other populations with HIV infection or other resistance profiles.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Lamivudine/Dolutegravir in Virologically Suppressed Subjects With Expected or Confirmed Resistance to Lamivudine — NCT04880785.
• Registry record last updated 2026-09-09; status last verified 2026-07.
• Results first posted 2026-09-09.
• 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.

18. Record Summary

The registry record identifies NCT04880785 as a completed phase II study of dolutegravir plus lamivudine in people with HIV infection and past or suspected lamivudine resistance. It describes the study as phase IIa, open-label, single-arm, and multicentric, with enrollment of 167 participants. The regimen was dolutegravir 50 mg with lamivudine 300 mg once daily during 96 weeks.

The primary outcome concerns maintenance of virologic suppression at Week 48 in participants whose baseline proviral DNA population sequencing did not detect lamivudine resistance-associated mutations. The record reports eight participants without Week 48 data and gives details on the classification of some discontinuations. It does not report a complete primary outcome estimate or its precision.

The registry lists multiple secondary outcomes relating to virologic control, resistance, time to failure, subgroups, and sequencing thresholds. Their results and a formal statistical analysis plan are not reported in the registry record. The study has no concurrent comparator, so its reported design supports descriptive interpretation of the treated group rather than a randomized comparison.