HIV, HIV Infections
Conditions
Keywords
Human Immunodeficiency Virus (HIV)-1, Dolutegravir, Lamivudine, Bictegravir, Emtricitabine, Tenofovir alafenamide, Dovato, Biktarvy, Switch study, ≥ 50 years
Brief summary
The study aims at evaluating the maintenance of virologic suppression of dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC) at Week 48 post-switch from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in participants living with Human Immunodeficiency Virus Type 1 (HIV-1) who are of at least 50 years of age and above.
Interventions
DRUGDTG/3TC
DTG/3TC FDC will be administered once daily.
Sponsors
ViiV Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants living with HIV-1 with documented plasma HIV-1 RNA \<50 c/mL within 3 months prior to Screening. * Participants must have been on uninterrupted antiretroviral therapy (ART) for ≥1 year (except for brief periods \[less than 30 days\] where all ART was stopped due to tolerability and/or safety concerns). * Participants must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening. * Participants with plasma HIV-1 RNA \<50 c/mL at Screening. * Participants with no known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL). * Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor.
Exclusion criteria
* Women participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study. * Participants with any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease, EXCEPT cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/cubic millimetre (mm\^3) are not exclusionary. * Participants with signs and symptoms which, in the opinion of the Investigator, are suggestive of active severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection within 14 days prior to enrolment. * Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification. * Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: 1. Participants positive for HBsAg are excluded; 2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded; 3. Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. * Participants with unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). * Participants with history of liver cirrhosis with or without hepatitis viral co-infection. * Participants with untreated syphilis infection (positive rapid plasma reagin \[RPR\] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible. * Participants with history or presence of allergy or intolerance to the study treatment or their components or drugs of their class or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. * Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia. * Participants who in the investigator's judgment, poses a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk. * Participants with any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major Integrase strand transfer inhibitor (INSTI) resistance associated mutation in any available prior resistance genotype assay test result. All available historical resistance reports with HIV-1 reverse transcriptase or integrase genotypic data must be provided to ViiV after screening and before enrollment for review by ViiV Virology. * Participants with any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities. * Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN and bilirubin ≥1.5xULN (with greater than \[\>\]35 percentage \[%\] direct bilirubin). * Participant has estimated creatine clearance \<30 millilitres per minute (mL/min) per 1.73 square meter (m\^2) using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr\_R) method.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Greater Than or Equal to (>=)50 Copies/Millilitre (c/mL) at Week 48 | At Week 48 | Participants with HIV-1 RNA \>= 50 c/mL were evaluated. Virologic outcome was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the Week 48 Window. The analysis was done using the modified Snapshot algorithm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Plasma HIV-1 RNA >= 50 c/mL at Week 24 | At Week 24 | The number of participants with plasma HIV-1 RNA \>/=50 c/mL at Week 24 was analyzed using the Snapshot Algorithm. |
| Number of Participants With Plasma HIV-1 RNA >= 50 c/mL at Week 96 | At Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Number of Participants With Plasma HIV-1 RNA Less Than (<) 50 c/mL at Week 24 | At Week 24 | The number of participants with plasma HIV-1 RNA \<50 c/mL at Week 24 was analyzed using the Snapshot Algorithm. |
| Number of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 48 | At Week 48 | The number of participants with plasma HIV-1 RNA \< 50 c/mL at Week 48 was analyzed using the modified Snapshot Algorithm. |
| Number of Participants With Plasma HIV-1 RNA < 50 c/mL at Week 96 | At Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Absolute Values for Cluster of Differentiation 4 (CD4+) Cells Count at Week 24 | At Week 24 | — |
| Absolute Values for CD4+ Cells Count at Week 48 | At Week 48 | — |
| Absolute Values for CD4+ Cells Count at Week 96 | At Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Absolute Values for CD4: Cluster of Differentiation 8 (CD8) Ratio at Week 24 | At Week 24 | The CD4/CD8 ratio is defined as a numerical representation of the proportion of CD4+ T cells to CD8+ T cells in the blood. |
| Absolute Values for CD4:CD8 Ratio at Week 48 | At Week 48 | The CD4/CD8 ratio is defined as a numerical representation of the proportion of CD4+ T cells to CD8+ T cells in the blood. |
| Absolute Values for CD4:CD8 Ratio at Week 96 | At Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Change From Baseline in CD4+ Cells Count at Week 24 | At Week 24 compared to Baseline | — |
| Change From Baseline in CD4+ Cells Count at Week 48 | At Week 48 compared to Baseline | — |
| Change From Baseline in CD4+ Cells Count at Week 96 | At Week 96 compared to baseline | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Change From Baseline in CD4:CD8 Ratio at Week 24 | At Week 24 compared to Baseline | The CD4/CD8 ratio is defined as a numerical representation of the proportion of CD4+ T cells to CD8+ T cells in the blood. |
| Change From Baseline in CD4:CD8 Ratio at Week 48 | At Week 48 compared to Baseline | The CD4/CD8 ratio is defined as a numerical representation of the proportion of CD4+ T cells to CD8+ T cells in the blood. |
| Change From Baseline in CD4:CD8 Ratio at Week 96 | At Week 96 compared to baseline | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Number of Participants With Disease Progression (HIV-associated Conditions, AIDS, and Death) Through Week 24 | Up to Week 24 | Occurrence of disease progression was evaluated through HIV-associated conditions and incidence of disease progression to United States Centers for Disease Control and Prevention (CDC) stage 3 or death. |
| Number of Participants With Disease Progression (HIV-associated Conditions, AIDS, and Death) Through Week 48 | Up to Week 48 | — |
| Number of Participants With Disease Progression (HIV-associated Conditions, AIDS, and Death) Through Week 96 | Week 96 | — |
| Number of Participants With Viral Resistance After Meeting Confirmed Virologic Withdrawal (CVW) Criterion | Up to Week 48 | Confirmed virologic withdrawal criteria is defined as two consecutive assessments with HIV-1 RNA greater than or equal to (\>=)200 c/mL after Day 1 visit. |
| Number of Participants With Viral Resistance After Meeting CVW Criterion | From Week 48 to Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Number of Participants With Treatment Related Non-serious Adverse Events (AEs) | Up to Week 48 | A treatment related non-serious AE is defined as any untoward medical occurrence in a clinical study participant considered related to the study treatment. Any = occurrence of the event regardless of intensity grade |
| Number of Participants With Treatment Related Non-serious AEs | From Week 48 to Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Number of Participants With Any Serious Adverse Events (SAEs) | Up to Week 48 | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement. Any = occurrence of the event regardless of intensity grade. |
| Number of Participants With SAEs | From Week 48 to Week 96 | Data not available at the time of posting, will be updated at the final results disclosure stage. |
| Number of Participants With AEs Leading to Treatment Discontinuation | Up to Week 48 | — |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Mexico, Netherlands, Portugal, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Analysis presented includes data up to Primary Completion (Week 48 of the study). Additional results will be provided within one year of study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.2 Years STANDARD_DEVIATION 7.46 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 68 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants |
| Race/Ethnicity, Customized White | 125 Participants |
| Sex: Female, Male Female | 88 Participants |
| Sex: Female, Male Male | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 205 |
| other Total, other adverse events | 69 / 205 |
| serious Total, serious adverse events | 26 / 205 |
Outcome results
None listed