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

• 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.
• 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.
• 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.

Primary outcomes

• 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 outcomes

• 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]

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• 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 (Primary), Count of participants, Participants: Treatment-naïve Participants 19
• Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 48 Weeks After 2DR Initiation (Primary), Count of participants, Participants: Treatment-naïve Participants 19
• Number of Treatment-naïve Participants With HIV-RNA Levels <50 c/mL at 96 Weeks After 2DR Initiation (Primary), Count of participants, Participants: Treatment-naïve Participants 20
• Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 24 (Primary), Count of participants, Participants: Prior Virological Failure Participants 14
• Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 48 (Primary), Count of participants, Participants: Prior Virological Failure Participants 11
• Number of Treatment-experienced Viremic Participants With HIV-RNA Levels <50 c/mL at Week 96 (Primary), Count of participants, Participants: Prior Virological Failure Participants 10
• Number of Treatment-naïve Participants Experiencing Virologic Failure (VF) [Up to 24 Weeks] (Primary), Count of participants, Participants: Treatment-naïve Participants 0
• Number of Treatment-naïve Participants Experiencing VF [Up to 48 Weeks] (Primary), Count of participants, Participants: Treatment-naïve Participants 0
• Number of Treatment-naïve Participants Experiencing VF [Up to 96 Weeks] (Primary), Count of participants, Participants: Treatment-naïve Participants 0
• Number of Stable Switch Participants With VF Within the First 24 Weeks (Primary), Count of participants, Participants: Stable Switch Participants 1
• Number of Stable Switch Participants With VF Within the First 48 Weeks (Primary), Count of participants, Participants: Stable Switch Participants 3
• Number of Stable Switch Participants With VF Within the First 96 Weeks (Primary), Count of participants, Participants: Stable Switch Participants 10
• Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 24 Weeks] (Primary), Count of participants, Participants: Prior Virological Failure Participants 0
• Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 48 Weeks] (Primary), Count of participants, Participants: Prior Virological Failure Participants 1
• Number of Treatment-experienced Viremic Participants Experiencing VF [Up to 96 Weeks] (Primary), Count of participants, Participants: Prior Virological Failure Participants 3
• Number of Participants With HIV RNA Levels >=200 c/mL After 24 Weeks, 48 Weeks and 96 Weeks (Secondary), Count of participants, Participants: Treatment-naïve Participants 0; Stable Switch Participants 1; Prior Virological Failure Participants 2
• Number of Participants With Low Level Viremia (Secondary), Count of participants, Participants: Treatment-naïve Participants 1; Stable Switch Participants 6; Prior Virological Failure Participants 0
• Time to Virologic Suppression Among Treatment-naïve Participants and Treatment-experienced Viremic Participants, Who Achieved Suppression (Secondary), Median, Months: Treatment-naïve Participants NA (NA to NA); Prior Virological Failure Participants NA (NA to NA)
• Time to Virologic Failure in the Stable Switch Population (Secondary), Median, Months: Stable Switch Participants NA (NA to NA)
• Number of Participants With Emergent Resistance Mutations Following Virologic Failure (VF) Events (Secondary), Count of participants, Participants: Treatment-naïve Participants 0; Stable Switch Participants 0; Prior Virological Failure Participants 0
• 6 more outcome measures not shown.

Adverse events

Time frame: Non-serious AEs and serious AEs were collected from the day of the first exposure to the 2DR (date when 2DR was prescribed) until week 96, or at the earliest of the following events: date of last study contact, date of 2DR treatment discontinuation (except if the participant was switched to another 2DR), or the date of lost to follow-up.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2018-06-18)
• Statistical Analysis Plan (PDF, 2021-05-16)

• GSK Clinical Trials, Study director, ViiV Healthcare