'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
- 1
- 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 Subjects receiving 2DR treatment Lamivudine (3TC) Data will be collected from HIV positive male or female adult subjects who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014. Subjects receiving 2DR treatment Dolutegravir (DTG) Data will be collected from HIV positive male or female adult subjects who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014. Subjects receiving 2DR treatment Rilpivirine (RPV) Data will be collected from HIV positive male or female adult subjects who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014.
- Primary Outcome Measures
Name Time Method Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 48 Week 48 Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels \<50 c/mL at Week 48 will be assessed.
Number of subjects who lose virologic control within the first 24 weeks after switching to a 2-DR Week 24 Virologic control is defined as 2 consecutive HIV RNA levels \>50 c/mL or HIV RNA \>50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.
Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 copies/milliliter (c/mL) at Week 24 Week 24 Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels \<50 c/mL at Week 24 will be assessed.
Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 96 Week 96 Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels \<50 c/mL at Week 96 will be assessed.
Number of subjects who lose virologic control within the first 48 weeks after switching to a 2-DR Week 48 Virologic control is defined as 2 consecutive HIV RNA levels \>50 c/mL or HIV RNA \>50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.
Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 96 Week 96 Number of treatment-experienced subjects with HIV-RNA levels \<50 c/mL at Week 96 will be assessed.
Number of subjects who lose virologic control within the first 96 weeks after switching to a 2-DR Week 96 Virologic control is defined as 2 consecutive HIV RNA levels \>50 c/mL or HIV RNA \>50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.
Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 24 Week 24 Number of treatment-experienced subjects with HIV-RNA levels \<50 c/mL at Week 24 will be assessed.
Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 48 Week 48 Number of treatment-experienced subjects with HIV-RNA levels \<50 c/mL at Week 48 will be assessed.
- Secondary Outcome Measures
Name Time Method Number of subjects with resistance profile in case of virologic failure Up to Week 96 Subjects with virologic rebound or virologic non-response will be considered as failure. Results of all HIV resistance tests performed before and during antiretroviral treatment will be evaluated to analyze resistance profile in case of virologic failure.
Number of subjects with HIV RNA >200 c/mL after 48 weeks Week 48 Subjects will be assessed for HIV RNA \>200 c/mL after Week 48.
Number of subjects with HIV RNA >200 c/mL after 96 weeks Week 96 Subjects will be assessed for HIV RNA \>200 c/mL after Week 96.
Number of subjects with low level viremia Up to Week 96 Low level viremia is defined as virologic load \>50 and \<200 c/mL. Number of subjects with low level viremia will be assessed at indicated time points.
Number of subjects with stable switch while virologically suppressed Up to Week 96 A switching option for those with HIV RNA suppression on current treatment will be called as 'Stable switch'. Number of subjects with stable switch while virologically suppressed will be analyzed.
Time to virologic suppression Up to Week 96 Virologic suppression is defined as viral load \< 50 c/mL at the end of 6months/12months/18 months or as pre-specified.
Number of subjects with HIV RNA >200 c/mL after 24 weeks Week 24 Subjects will be assessed for HIV RNA \>200 c/mL after Week 24.
Time to virologic failure Up to Week 96 Time to virologic failure in the stable switch Population will be assessed. Subjects with virologic rebound or virologic non-response will be considered as failure.
Number of subjects with Switch after Failure Up to Week 96 Subjects with virologic rebound or virologic non-response will be considered as failure. Number of subjects with Switch after Failure will be analyzed.
Number of subjects switching for safety reasons Up to Week 96 Number of subjects switching for safety reasons including tolerability, toxicity and other reasons will be evaluated.
Number of subjects with adverse events (AEs) and serious AEs (SAEs) Up to Week 96 An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, 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 will be categorized as SAE.
cluster of differentiation (CD)4+ and CD8+ T cell counts Up to Week 96 All available CD4 and CD8 results since first starting 2DR treatment will be collected to analyze CD4+ and CD8+ T cell counts.
CD4/CD8 ratio at each time point Up to Week 96 All available CD4 and CD8 results since first starting 2DR treatment will be collected to analyze CD4/CD8 ratio at each time point
Number of factors associated with plasma HIV-RNA > 50 c/mL Up to Week 96 If number of failure allows, analysis to assess factors associated with success at week 96 in naïve and treatment experienced populations and with virologic failure in population switching with HIV RNA suppression will be analyzed.
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Barcelona, Spain