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

NCT04019873 | Completed Results

• 1 other identifier: 207859
• Study Type: observational
• Target: 774
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Keywords

2DR; HIV; Lamivudine; COMBINE-2; Dolutegravir

Outcome Measures

Primary Outcomes (15)

• 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

  At Week 24

• Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 48 Weeks After 2DR Initiation

  At Week 48

• Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 96 Weeks After 2DR Initiation

  At Week 96

• Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 24

  At Week 24

• Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 48

  At Week 48

• Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 96

  At Week 96

• Number of Treatment-naïve Participants Experiencing Virologic Failure (VF) [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]

  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]

  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

  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

  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

  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]

  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]

  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]

  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 Outcomes (11)

• Number of Participants With HIV RNA Levels >=200 c/mL After 24 Weeks, 48 Weeks and 96 Weeks

  At Week 24, Week 48 and Week 96

• Number of Participants With Low Level Viremia

  At Week 24, Week 48 and Week 96

• Time to Virologic Suppression Among Treatment-naïve Participants and Treatment-experienced Viremic Participants, Who Achieved Suppression

  Up to Week 96

• Time to Virologic Failure in the Stable Switch Population

  Up to Week 96

• Number of Participants With Emergent Resistance Mutations Following Virologic Failure (VF) Events

  Up to Week 96

Study Arms (3)

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); Drug: Lamivudine (3TC); Drug: Rilpivirine (RPV)

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); Drug: Lamivudine (3TC); Drug: Rilpivirine (RPV)

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); Drug: Lamivudine (3TC); Drug: Rilpivirine (RPV)

Interventions

Dolutegravir (DTG) DRUG

DTG is a 2nd generation integrase strand transfer inhibitor. Subjects receiving DTG as a part of 2DR treatment will be included in the study.

Prior virological failure participants; Stable switch participants; Treatment-naïve participants

Lamivudine (3TC) DRUG

3TC is a nucleoside reverse transcriptase inhibitor. Subjects receiving 3TC as a part of 2DR treatment will be included in the study.

Prior virological failure participants; Stable switch participants; Treatment-naïve participants

Rilpivirine (RPV) DRUG

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; Stable switch participants; Treatment-naïve participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Barcelona, 08041, Spain

Location

MeSH Terms

Conditions

HIV Infections

Interventions

dolutegravir; Lamivudine; Rilpivirine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Nitriles; Organic Chemicals

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: July 15, 2019
• Study Start: November 18, 2019
• Primary Completion: April 14, 2023
• Study Completion: December 5, 2023
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)