'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT04019873
- Lead Sponsor
- ViiV Healthcare
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 774
- 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.
- No specific exclusion criteria
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Treatment-naïve participants Dolutegravir (DTG) 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. Treatment-naïve participants Lamivudine (3TC) 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. Treatment-naïve participants Rilpivirine (RPV) 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. Stable switch participants Dolutegravir (DTG) 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. Stable switch participants Lamivudine (3TC) 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. Stable switch participants Rilpivirine (RPV) 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. Prior virological failure participants Dolutegravir (DTG) 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. Prior virological failure participants Lamivudine (3TC) 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. Prior virological failure participants Rilpivirine (RPV) 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.
- Primary Outcome Measures
Name Time Method 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] 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).
Number of Treatment-naïve Participants Experiencing VF [Up to 48 Weeks] 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).
Number of Treatment-naïve Participants Experiencing VF [Up to 96 Weeks] 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).
Number of Stable Switch Participants With VF Within the First 24 Weeks 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.
Number of Stable Switch Participants With VF Within the First 48 Weeks 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.
Number of Stable Switch Participants With VF Within the First 96 Weeks 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.
Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 24 Weeks] 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.
Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 48 Weeks] 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.
Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 96 Weeks] 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.
- Secondary Outcome Measures
Name Time Method 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 Low level viremia was defined as virologic load \>=50 and \<200 c/mL.
Time to Virologic Suppression Among Treatment-naïve Participants and Treatment-experienced Viremic Participants, Who Achieved Suppression 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.
Time to Virologic Failure in the Stable Switch Population 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).
Number of Participants With Emergent Resistance Mutations Following Virologic Failure (VF) Events 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 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.
Number of Participants Who Discontinue Their Baseline 2DR and Who Switch Following Virologic Failure Up to Week 96 Virologic rebound or virologic non-response in participants, was considered as virologic failure.
Number of Participants Who Discontinue Their Baseline 2DR Who Are Switching for Safety or Other Reasons Up to Week 96 Safety reasons include tolerability, toxicity and other reasons.
Number of Participants With AEs and SAEs 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.
Cluster of Differentiation (CD)4+ and CD8+ T Cell Counts At baseline (Week 0), Week 24, Week 48 and Week 96 CD4/CD8 Ratio At baseline (Week 0), Week 24, Week 48 and Week 96
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Barcelona, Spain