'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor

December 17, 2024 updated by: ViiV Healthcare
Dolutegravir (DTG) is a well-tolerated 2nd generation integrase strand transfer inhibitor (INSTI); rilpivirine (RPV) is a well-tolerated non- nucleoside reverse transcriptase inhibitors (NNRTI) and lamivudine (3TC) is a nucleoside reverse transcriptase inhibitors (NRTIs). This study aims to gather the real-world evidence to evaluate effectiveness of the two-drug regimen (2DR). This is a multi-site observational study in subjects who have started and/or who plan to initiate 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor. The study does not require any changes to the routine standard of care that subjects receive. Approximately 500 eligible subjects will be included from potential investigational sites across Europe and data from them will be collected either retrospectively or prospectively.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
774

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08041
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of HIV positive male or female subjects aged 18 years or over and who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014 onwards as a first-line treatment among naïve subjects, or a switching option for those with HIV RNA suppression on current treatment (stable switches), or a second-line treatment for those with virological failure on prior treatment.

Description

Inclusion Criteria:

  • HIV positive male or female subjects aged 18 years or over and who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014 onwards as a first-line treatment among naïve subjects, or a switching option for those with HIV RNA suppression on current treatment (stable switches), or a second-line treatment for those with virological failure on prior treatment.

Exclusion Criteria:

  • No specific exclusion criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Treatment-naïve participants
Participants received a two-drug regimen (2DR) consisting of an integrase inhibitor plus a reverse transcriptase inhibitor, as a first-line treatment for Human Immunodeficiency Virus (HIV) infection.
Drug: Dolutegravir (DTG)
DTG is a 2nd generation integrase strand transfer inhibitor. Subjects receiving DTG as a part of 2DR treatment will be included in the study.
Drug: Lamivudine (3TC)
3TC is a nucleoside reverse transcriptase inhibitor. Subjects receiving 3TC as a part of 2DR treatment will be included in the study.
Drug: Rilpivirine (RPV)
RPV is a non-nucleoside reverse transcriptase inhibitor. Subjects receiving RPV as part of 2DR treatment will be included in the study.
Stable switch participants
Participants received a two-drug regimen (2DR) consisting of an integrase inhibitor plus a reverse transcriptase inhibitor, as a switching treatment option for HIV infection, whilst virologically suppressed (whilst having HIV RNA suppression) on current treatment.
Drug: Dolutegravir (DTG)
DTG is a 2nd generation integrase strand transfer inhibitor. Subjects receiving DTG as a part of 2DR treatment will be included in the study.
Drug: Lamivudine (3TC)
3TC is a nucleoside reverse transcriptase inhibitor. Subjects receiving 3TC as a part of 2DR treatment will be included in the study.
Drug: Rilpivirine (RPV)
RPV is a non-nucleoside reverse transcriptase inhibitor. Subjects receiving RPV as part of 2DR treatment will be included in the study.
Prior virological failure participants
Participants received a two-drug regimen (2DR) consisting of an integrase inhibitor plus a reverse transcriptase inhibitor, as a second-line treatment for HIV infection, due to virological failure (VF) on prior treatment.
Drug: Dolutegravir (DTG)
DTG is a 2nd generation integrase strand transfer inhibitor. Subjects receiving DTG as a part of 2DR treatment will be included in the study.
Drug: Lamivudine (3TC)
3TC is a nucleoside reverse transcriptase inhibitor. Subjects receiving 3TC as a part of 2DR treatment will be included in the study.
Drug: Rilpivirine (RPV)
RPV is a non-nucleoside reverse transcriptase inhibitor. Subjects receiving RPV as part of 2DR treatment will be included in the study.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Treatment-naïve Participants With Human Immunodeficiency Virus Ribonucleic Acid (HIV-RNA) Levels Less Than (<)50 Copies/Milliliter (c/mL) at 24 Weeks After 2DR (Two-drug Regimen) Initiation
Time Frame: At Week 24
At Week 24
Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 48 Weeks After 2DR Initiation
Time Frame: At Week 48
At Week 48
Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 96 Weeks After 2DR Initiation
Time Frame: At Week 96
At Week 96
Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 24
Time Frame: At Week 24
At Week 24
Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 48
Time Frame: At Week 48
At Week 48
Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 96
Time Frame: At Week 96
At Week 96
Number of Treatment-naïve Participants Experiencing Virologic Failure (VF) [Up to 24 Weeks]
Time Frame: Up to 24 weeks
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA level greater than or equal to [>=] 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL>=200 copies/mL after at least 24 weeks of treatment).
Up to 24 weeks
Number of Treatment-naïve Participants Experiencing VF [Up to 48 Weeks]
Time Frame: Up to 48 weeks
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA level greater than or equal to [>=] 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL>=200 copies/mL after at least 48 weeks of treatment).
Up to 48 weeks
Number of Treatment-naïve Participants Experiencing VF [Up to 96 Weeks]
Time Frame: Up to 96 weeks
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA level greater than or equal to [>=] 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL>=200 copies/mL after at least 96 weeks of treatment).
Up to 96 weeks
Number of Stable Switch Participants With VF Within the First 24 Weeks
Time Frame: Up to Week 24
VF was defined as 2 consecutive HIV RNA >=50 c/mL or 1 HIV RNA >50c/mL followed by study treatment discontinuation or missing value.
Up to Week 24
Number of Stable Switch Participants With VF Within the First 48 Weeks
Time Frame: Up to Week 48
VF was defined as 2 consecutive HIV RNA >=50 c/mL or 1 HIV RNA >50c/mL followed by study treatment discontinuation or missing value.
Up to Week 48
Number of Stable Switch Participants With VF Within the First 96 Weeks
Time Frame: Up to Week 96
VF was defined as 2 consecutive HIV RNA >=50 c/mL or 1 HIV RNA >50c/mL followed by study treatment discontinuation or missing value.
Up to Week 96
Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 24 Weeks]
Time Frame: Up to 24 weeks
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA >= 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL >=200 copies/mL after at least 24 weeks of treatment). Treatment-experienced viremic participants refers to individuals who have previously undergone HIV treatment but had virological failure in prior treatment.
Up to 24 weeks
Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 48 Weeks]
Time Frame: Up to 48 weeks
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA >= 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL >=200 copies/mL after at least 48 weeks of treatment). Treatment-experienced viremic participants refers to individuals who have previously undergone HIV treatment but had virological failure in prior treatment.
Up to 48 weeks
Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 96 Weeks]
Time Frame: Up to 96 weeks
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA >= 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL >=200 copies/mL after at least 96 weeks of treatment). Treatment-experienced viremic participants refers to individuals who have previously undergone HIV treatment but had virological failure in prior treatment.
Up to 96 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With HIV RNA Levels >=200 c/mL After 24 Weeks, 48 Weeks and 96 Weeks
Time Frame: At Week 24, Week 48 and Week 96
At Week 24, Week 48 and Week 96
Number of Participants With Low Level Viremia
Time Frame: At Week 24, Week 48 and Week 96
Low level viremia was defined as virologic load >=50 and <200 c/mL.
At Week 24, Week 48 and Week 96
Time to Virologic Suppression Among Treatment-naïve Participants and Treatment-experienced Viremic Participants, Who Achieved Suppression
Time Frame: Up to Week 96
Suppression of VL was evaluated at 24 weeks, 48 weeks and 96 weeks and time to virologic suppression was planned to be evaluated until 96 weeks.
Up to Week 96
Time to Virologic Failure in the Stable Switch Population
Time Frame: Up to Week 96
VF was defined as virologic rebound (after achieving suppression, 2 consecutive HIV RNA level greater than or equal to [>=] 50 copies/mL or 1 HIV RNA level >=50 copies/mL followed by study treatment discontinuation) or virologic non-response (2 consecutive VL>=200 copies/mL after at least 48 weeks of treatment).
Up to Week 96
Number of Participants With Emergent Resistance Mutations Following Virologic Failure (VF) Events
Time Frame: Up to Week 96
Up to Week 96
Number of Participants Who Discontinue Their Baseline 2DR and Who Stable Switch to a Different Regimen While Virologically Suppressed (HIV RNA <50 Copies/mL) at Switch
Time Frame: Up to Week 96
A stable switch was defined as a switching option for participants with HIV RNA suppression on current treatment with viral load <50 c/mL at time of switch.
Up to Week 96
Number of Participants Who Discontinue Their Baseline 2DR and Who Switch Following Virologic Failure
Time Frame: Up to Week 96
Virologic rebound or virologic non-response in participants, was considered as virologic failure.
Up to Week 96
Number of Participants Who Discontinue Their Baseline 2DR Who Are Switching for Safety or Other Reasons
Time Frame: Up to Week 96
Safety reasons include tolerability, toxicity and other reasons.
Up to Week 96
Number of Participants With AEs and SAEs
Time Frame: Up to Week 96
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward event resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Determination of an event as AE or SAE was at the discretion of the treating clinician and taken from the medical record.
Up to Week 96
Cluster of Differentiation (CD)4+ and CD8+ T Cell Counts
Time Frame: At baseline (Week 0), Week 24, Week 48 and Week 96
At baseline (Week 0), Week 24, Week 48 and Week 96
CD4/CD8 Ratio
Time Frame: At baseline (Week 0), Week 24, Week 48 and Week 96
At baseline (Week 0), Week 24, Week 48 and Week 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ViiV Healthcare

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: GSK Clinical Trials, ViiV Healthcare

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 18, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 14, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 5, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 19, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 15, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 207859

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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