Clinical trial NCT04019873: 'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor
Official title: 'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: 2DR
HIV
Lamivudine
COMBINE-2
Dolutegravir
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2019-07-15
Enrollment: 774
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: At Week 24
measure: Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 48 Weeks After 2DR Initiation
timeFrame: At Week 48
measure: Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 96 Weeks After 2DR Initiation
timeFrame: At Week 96
measure: Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 24
timeFrame: At Week 24
measure: Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 48
timeFrame: At Week 48
measure: Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 96
timeFrame: At Week 96
measure: Number of Treatment-naïve Participants Experiencing Virologic Failure (VF) [Up to 24 Weeks]
timeFrame: Up to 24 weeks
measure: Number of Treatment-naïve Participants Experiencing VF [Up to 48 Weeks]
timeFrame: Up to 48 weeks
measure: Number of Treatment-naïve Participants Experiencing VF [Up to 96 Weeks]
timeFrame: Up to 96 weeks
measure: Number of Stable Switch Participants With VF Within the First 24 Weeks
timeFrame: Up to Week 24
measure: Number of Stable Switch Participants With VF Within the First 48 Weeks
timeFrame: Up to Week 48
measure: Number of Stable Switch Participants With VF Within the First 96 Weeks
timeFrame: Up to Week 96
measure: Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 24 Weeks]
timeFrame: Up to 24 weeks
measure: Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 48 Weeks]
timeFrame: Up to 48 weeks
measure: Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 96 Weeks]
timeFrame: Up to 96 weeks
Secondary outcomes:
measure: Number of Participants With HIV RNA Levels >=200 c/mL After 24 Weeks, 48 Weeks and 96 Weeks
timeFrame: At Week 24, Week 48 and Week 96
measure: Number of Participants With Low Level Viremia
timeFrame: At Week 24, Week 48 and Week 96
measure: Time to Virologic Suppression Among Treatment-naïve Participants and Treatment-experienced Viremic Participants, Who Achieved Suppression
timeFrame: Up to Week 96
measure: Time to Virologic Failure in the Stable Switch Population
timeFrame: Up to Week 96
measure: Number of Participants With Emergent Resistance Mutations Following Virologic Failure (VF) Events
timeFrame: Up to Week 96
measure: 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
timeFrame: Up to Week 96
measure: Number of Participants Who Discontinue Their Baseline 2DR and Who Switch Following Virologic Failure
timeFrame: Up to Week 96
measure: Number of Participants Who Discontinue Their Baseline 2DR Who Are Switching for Safety or Other Reasons
timeFrame: Up to Week 96
measure: Number of Participants With AEs and SAEs
timeFrame: Up to Week 96
measure: Cluster of Differentiation (CD)4+ and CD8+ T Cell Counts
timeFrame: At baseline (Week 0), Week 24, Week 48 and Week 96
measure: CD4/CD8 Ratio
timeFrame: At baseline (Week 0), Week 24, Week 48 and Week 96
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: