HIV Infections
Conditions
Keywords
HIV infection, GSK3640254, Nucleoside Reverse Transcriptase Inhibitor, Dolutegravir, Abacavir (ABC)/Lamivudine (3TC), Emtricitabine (FTC)/tenofovir alafenamide (TAF), Maturation Inhibitor
Brief summary
This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses \[100, 150 and 200 milligrams {mg}\]), active controlled clinical trial. It aims to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine \[ABC/3TC\] or emtricitabine/tenofovir alafenamide \[FTC/TAF\]).
Interventions
DRUGGSK3640254
GSK3640254 was available as a 25 mg and 100 mg tablets to be administered via oral route.
DRUGABC/3TC
ABC/3TC was available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.
DRUGFTC/TAF
FTC/TAF was available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.
DRUGDolutegravir
Dolutegravir was available as a 50 mg tablet to be administered via oral route.
DRUGPlacebo
Placebo matching GSK3640254 was administered in the form of tablets via oral route.
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study treatment assignments was not blinded (GSK3640254 versus Dolutegravir control arm). However, the dose level of GSK3640254 in each of the treatment arms containing GSK3640254 was blinded to the research participants and all study personnel during the study. The Sponsor personnel remained blinded until the database lock for the Week 24 analysis.
Intervention model description
This is a randomized, multicenter, parallel group study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be 18 years of age inclusive, at the time of signing the informed consent. * Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy) received after the diagnosis of HIV-1 infection (for example \[e.g.\], use of Pre-exposure prophylaxis \[PreP\] meets inclusion. * Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (\>=)1000 c/mL. * Screening CD4+ T-cell count \>=250 cells/mm\^3. * Antiviral susceptibility to the NRTI backbone selected should be demonstrated * Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index (BMI) greater than (\>)18.5 kg/meter square (m\^2).Calculations utilized sex assigned at birth * Participants who are male at birth and participants who are female at birth. * Participants who are female at birth: Contraceptive use by participant who are female at birth should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • A participant who was female at birth was eligible to participate if they were not pregnant or breastfeeding, and one of the following conditions applies: * Was a participant of non-childbearing potential (PONCBP) * Or was a POCBP and using an acceptable contraceptive method during the study intervention period (at a minimum until after the last dose of study intervention). * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * For participants enrolled in France: a participant was eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria
* Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy. * 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. * Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion. * Known history of liver cirrhosis with or without viral hepatitis co-infection. * 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). * History of ongoing or clinically relevant hepatitis within the previous 6 months. * History of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation. * Any history of significant underlying psychiatric disorder, in the opinion of the Investigator or ViiV Medical Monitor, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder or a clinical assessment of suicidality based on the responses on the Columbia-Suicide Severity Rating Scale (eCSSRS). * Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment. * Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the Investigator or ViiV Medical Monitor (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant. * A pre-existing condition, in the opinion of the Investigator or ViiV Medical Monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease \[GERD\], gastric ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, or with the absorption, metabolism, and/or excretion of the study drugs or render the participant unable to take oral study treatment. * Myocardial infarction in the past 3 months. * Familial or personal history of long QT syndrome or sudden cardiac death. * Medical history, current or historical, of significant cardiac arrhythmias or Electrocardiogram (ECG) findings which, in the opinion of the Investigator or ViiV Medical Monitor, will interfere with the safety of the participant. * Active Treatment for a viral infection other than HIV-1, such as Hepatitis B, with an agent that is active against HIV-1 (were known to be infected with HIV-1 after treatment for Hepatitis B was completed). * Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening. * Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant. * Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication. * Participants who are unwilling to stop any medications as required by the local lab test for Helicobacter (H.) pylori. * Participants who require concomitant medications known to be associated with a prolonged Corrected QT interval (QTc). * Exposure to an experimental drug, human blood product, monoclonal antibody, or vaccine (which does not have emergency, conditional or standard market authorization) within 28 days prior to the first dose of study treatment. * Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention (including an investigational Coronavirus Disease (COVID) vaccine) or any other type of medical research. * Any evidence of viral resistance based on the NRTI backbone selected. * Historical evidence (prior to study screening period) of the presence of resistance- associated mutations gag A364V or A364A/V. * Creatinine Clearance \<50 mL/minute. * Alanine aminotransferase (ALT) \>=3 times upper limit of normal (ULN) or ALT \>=2 times ULN and total bilirubin \>=1.5 times ULN. * Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and reflex HBV deoxyribonucleic acid (DNA) as follows: 1. Participants positive for HBsAg were excluded; 2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA on reflex testing were excluded. * Positive Hepatitis C antibody test result at Screening and positive on reflex to Hepatitis C RNA. * Positive test results for H. pylori; * Known or suspected active COVID-19 infection or contact with an individual with known COVID-19, within 14 days of study enrollment * Untreated syphilis infection (positive rapid plasma reagin \[RPR\] at Screening) without documentation of treatment. * Presence of moderate-to-severe hepatic impairment (Class B or C) as determined by Child-Pugh classification. * Any acute laboratory abnormality at Screening, which, in the opinion of the investigator or ViiV Medical Monitor, would preclude participation in the study of an investigational compound. * Urine Drug Screen positive (showing presence of): Amphetamines, Barbiturates, Cocaine, 3,4-Methyl enedioxy methamphetamine (MDMA) or Phencyclidine, or non-prescribed opiates, oxycodone, benzodiazepines, methadone, methamphetamines or tricyclic antidepressants. * Any clinically relevant Grade 4 laboratory abnormality at Screen, including results for creatine phosphokinase (CPK) and lipid abnormalities that lack a compelling explanation from the Investigator. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 28 days. * Exposure to more than 4 new investigational drugs or vaccines (exclusive of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential indication within 12 months prior to the first dosing day; * Treatment with radiation therapy or cytotoxic chemotherapeutic agents or any systemic immunosuppressive agent within 30 days of study drug administration or anticipated need for such treatment within the study; * ECG Heart Rate \<50 beats per minute (bpm) or \>100 bpm, or QT duration corrected for heart rate by Fridericia's formula (QTcF) \>450 milliseconds (msec). * For Portugal only: HIV-2 infection (either determined by prior testing, medical history, or obtained locally during the Screening window).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | At Week 24 | Percentage of participants with plasma HIV-1 RNA \<50 c/mL at week 24 was assessed using the Food and Drug Administration (FDA) snapshot algorithm to demonstrate the antiviral activity of GSK3640254 given in combination with either ABC/3TC or FTC/TAF compared to the reference treatment of DTG given in combination with either ABC/3TC or FTC/TAF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) and at Weeks 24 and 48 | Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log10) values for plasma HIV-1 RNA have been presented. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) and at Weeks 24 and 48 | Plasma samples were collected for quantitative analysis of HIV-1 RNA. log10 values for plasma HIV-1 RNA have been presented. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Baseline (Day 1) and at Weeks 24 and 48 | Blood samples were collected and CD4+ cell count was assessed using flow cytometry. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Baseline (Day 1) and at Weeks 24 and 48 | Blood samples were collected and CD4+ cell count was assessed using flow cytometry. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Number of Participants With Serious Adverse Events (SAEs) and Deaths | From Day 1 up to end of continued access to treatment post-study termination (Day 922) | An SAE was defined as any serious adverse event that, at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or any other situation according to medical or scientific judgment. |
| Number of Participants With Adverse Events (AEs) Leading to Treatment Discontinuation | From Day 1 up to end of continued access to treatment post-study termination (Day 922) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants who discontinued study treatment due to AEs are presented. |
| Number of Participants With AEs Based on Maximum Severity Grades | From Day 1 up to end of continued access to treatment post-study termination (Day 922) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The severity of AEs was defined as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.1 and was categorized into grades as following: Grade 1 - mild, Grade 2 - moderate, Grade 3 - severe, Grade 4 - Potentially life threatening and Grade 5 - Fatal. Higher grade indicates more severe condition. |
| Number of Participants With AEs of Special Interest (AESI) | From Day 1 up to end of continued access to treatment post-study termination (Day 922) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with AESI (gastrointestinal (GI), nervous system, and psychiatric AEs) are presented. |
| Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 | At Week 48 | Percentage of participants with plasma HIV-1 RNA \<50 c/mL at week 48 was assessed using the FDA snapshot algorithm to demonstrate the antiviral activity of GSK3640254 given in combination with either ABC/3TC or FTC/TAF compared to the reference treatment of DTG given in combination with either ABC/3TC or FTC/TAF. |
| Number of Participants With Phenotypic Resistance | Baseline (Day 1) and at Weeks 24 and 48 | Plasma samples were collected for resistance testing. Phenotypic testing was conducted in participants meeting PDVF criteria. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Week 2 | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254. Observed plasma concentration at the end of the dosing interval was determined directly from the concentration-time data. |
| Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | At Weeks 24 and 48 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254. Observed plasma concentration at the end of the dosing interval was determined directly from the concentration-time data. |
| Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval (AUC [0-tau]) of GSK3640254 at Steady State | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2 | Blood samples were collected at indicated time points for PK analysis of GSK3640254. |
| Maximum Observed Concentration (Cmax) of GSK3640254 at Steady State | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2 | Blood samples were collected at indicated time points for PK analysis of GSK3640254. |
| Observed Pre-dose Plasma Concentration (C0) of GSK3640254 at Steady State | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2 | Blood samples were collected at indicated time points for PK analysis of GSK3640254. Observed pre-dose plasma concentration was determined directly from the concentration-time data. |
| Time to Cmax (Tmax) of GSK3640254 at Steady State | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2 | Blood samples were collected at indicated time points for PK analysis of GSK3640254. Tmax was determined directly from the concentration-time data. |
| Steady State Oral Clearance (CLt/F) of GSK3640254 | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2 | Blood samples were collected at indicated time points for PK analysis of GSK3640254. |
| Number of Participants With Genotypic Resistance | Baseline (Day 1) and at Weeks 24 and 48 | Plasma samples were collected for resistance testing. Genotypic testing was conducted in participants meeting protocol-defined virologic failure (PDVF) criteria. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at specified time points have been analyzed. |
Countries
Argentina, Canada, France, Germany, Italy, Portugal, Russia, South Africa, Spain, Switzerland, United States
Participant flow
Recruitment details
This study assessed efficacy, safety and resistance of GSK3640254 in combination with ABC/3TC or FTC/TAF compared to dolutegravir + ABC/3TC or FTC/TAF in HIV-1 infected, treatment-naïve adults. The study was terminated by the sponsor at Week 48 as the sponsor determined further development of GSK3640254-containing daily oral regimen would not be differentiated enough from existing 2-drug daily oral regimens. Thus, secondary analyses at Week 96 and Week 144 were not evaluated.
Pre-assignment details
The changes from the planned subsequent analyses were presented as pre-specified in Statistical Analysis Plan. Safety analysis is presented based on the Entire Duration of Treatment Exposure period, which was defined from Day 1 up to end of continued access to treatment post-study termination (Day 922).
Participants by arm
| Arm | Count |
|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF Participants with human immunodeficiency virus type 1 (HIV-1), orally received one 100 mg tablet per day of GSK3640254 and two tablets per day of matching placebo in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day of 600 mg abacavir (ABC) / 300 mg lamivudine (3TC) OR 200 mg emtricitabine (FTC) / 25 mg tenofovir alafenamide (TAF) orally. | 40 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF Participants with HIV-1, orally received 150 mg (one 100 mg tablet + two 25 mg tablets per day) of GSK3640254 in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally. | 43 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF Participants with HIV-1, orally received two 100 mg tablets (200 mg) per day of GSK3640254 and one tablet per day of matching placebo in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally. | 42 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF Participants with HIV-1, orally received one 50 mg tablet per day of DTG in an open label setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally. | 36 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 5 | 2 |
| Overall Study | Lost to Follow-up | 2 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 0 | 2 |
| Overall Study | Study terminated by sponsor | 30 | 33 | 28 | 27 |
| Overall Study | Subject reached protocol-defined stopping criteria | 4 | 2 | 7 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | GSK3640254 150 mg + ABC/3TC or FTC/TAF | GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF |
|---|---|---|---|---|---|
| Age, Continuous | 35.0 YEARS STANDARD_DEVIATION 10.25 | 35.3 YEARS STANDARD_DEVIATION 9.85 | 33.7 YEARS STANDARD_DEVIATION 10.59 | 38.1 YEARS STANDARD_DEVIATION 12.54 | 32.8 YEARS STANDARD_DEVIATION 6.2 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized ASIAN | 5 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 26 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants |
| Race/Ethnicity, Customized MISSING | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized MIXED RACE | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized WHITE | 124 Participants | 29 Participants | 32 Participants | 31 Participants | 32 Participants |
| Sex: Female, Male Female | 38 Participants | 10 Participants | 12 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 123 Participants | 26 Participants | 30 Participants | 34 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 43 | 0 / 42 | 0 / 36 |
| other Total, other adverse events | 37 / 40 | 38 / 43 | 38 / 42 | 28 / 36 |
| serious Total, serious adverse events | 2 / 40 | 7 / 43 | 2 / 42 | 2 / 36 |
Outcome results
Primary
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24
Percentage of participants with plasma HIV-1 RNA \<50 c/mL at week 24 was assessed using the Food and Drug Administration (FDA) snapshot algorithm to demonstrate the antiviral activity of GSK3640254 given in combination with either ABC/3TC or FTC/TAF compared to the reference treatment of DTG given in combination with either ABC/3TC or FTC/TAF.
Time frame: At Week 24
Population: The analysis was performed on the Intent-to-Treat Exposed (ITT-E) population which included all randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 82.5 Percentage of participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 90.7 Percentage of participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 76.2 Percentage of participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24 | 91.7 Percentage of participants |
95% CI: [-24, 5.7]
95% CI: [-13.5, 11.6]
95% CI: [-31.2, 0.3]
Secondary
Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48
Blood samples were collected and CD4+ cell count was assessed using flow cytometry. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Day 1) and at Weeks 24 and 48
Population: The analysis was performed on the ITT-E population which included all randomized participants who received at least one dose of study intervention. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 480.3 Cells per cubic millimeter | Standard Deviation 171.72 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 48 | 749.9 Cells per cubic millimeter | Standard Deviation 328.28 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 24 | 717.5 Cells per cubic millimeter | Standard Deviation 222.91 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 509.7 Cells per cubic millimeter | Standard Deviation 207.13 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 48 | 702.6 Cells per cubic millimeter | Standard Deviation 258.65 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 24 | 643.5 Cells per cubic millimeter | Standard Deviation 202.27 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 24 | 689.8 Cells per cubic millimeter | Standard Deviation 316.64 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 478.7 Cells per cubic millimeter | Standard Deviation 204.04 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 48 | 747.3 Cells per cubic millimeter | Standard Deviation 313.15 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 514.1 Cells per cubic millimeter | Standard Deviation 240.88 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 48 | 705.2 Cells per cubic millimeter | Standard Deviation 221.18 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Counts at Weeks 24 and 48 | Week 24 | 724.8 Cells per cubic millimeter | Standard Deviation 403.99 |
Secondary
Absolute Values of HIV-1 RNA at Weeks 24 and 48
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log10) values for plasma HIV-1 RNA have been presented. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Day 1) and at Weeks 24 and 48
Population: The analysis was performed on the ITT-E population which included all randomized participants who received at least one dose of study intervention. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 48 | 1.602 Log 10 copies per milliliter | Standard Deviation 0.0536 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 24 | 1.619 Log 10 copies per milliliter | Standard Deviation 0.126 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.351 Log 10 copies per milliliter | Standard Deviation 0.5712 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 48 | 1.605 Log 10 copies per milliliter | Standard Deviation 0.0647 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.353 Log 10 copies per milliliter | Standard Deviation 0.6705 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 24 | 1.607 Log 10 copies per milliliter | Standard Deviation 0.0663 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 24 | 1.610 Log 10 copies per milliliter | Standard Deviation 0.0679 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 48 | 1.594 Log 10 copies per milliliter | Standard Deviation 0.0233 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.165 Log 10 copies per milliliter | Standard Deviation 0.6505 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 24 | 1.592 Log 10 copies per milliliter | Standard Deviation 0.0126 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.247 Log 10 copies per milliliter | Standard Deviation 0.6765 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Absolute Values of HIV-1 RNA at Weeks 24 and 48 | Week 48 | 1.590 Log 10 copies per milliliter | Standard Deviation 0 |
Secondary
Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval (AUC [0-tau]) of GSK3640254 at Steady State
Blood samples were collected at indicated time points for PK analysis of GSK3640254.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2
Population: The analysis was performed on the Intensive PK Population. Only those participants who received GSK3640254 and had data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval (AUC [0-tau]) of GSK3640254 at Steady State | 14995.7576 Hour*nanogram/ milliliter (h*ng/mL) | Geometric Coefficient of Variation 49.8 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval (AUC [0-tau]) of GSK3640254 at Steady State | 21212.2480 Hour*nanogram/ milliliter (h*ng/mL) | Geometric Coefficient of Variation 44.5 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval (AUC [0-tau]) of GSK3640254 at Steady State | 30708.2546 Hour*nanogram/ milliliter (h*ng/mL) | Geometric Coefficient of Variation 40.1 |
Secondary
Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48
Blood samples were collected and CD4+ cell count was assessed using flow cytometry. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Weeks 24 and 48
Population: The analysis was performed on the ITT-E population which included all randomized participants who received at least one dose of study intervention. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 480.3 Cells per cubic millimeter | Standard Deviation 171.72 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 48 | 292.4 Cells per cubic millimeter | Standard Deviation 264.16 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 24 | 241.3 Cells per cubic millimeter | Standard Deviation 191.26 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 509.7 Cells per cubic millimeter | Standard Deviation 207.13 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 48 | 189.2 Cells per cubic millimeter | Standard Deviation 216.1 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 24 | 129.3 Cells per cubic millimeter | Standard Deviation 233.07 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 24 | 202.3 Cells per cubic millimeter | Standard Deviation 271.98 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 478.7 Cells per cubic millimeter | Standard Deviation 204.04 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 48 | 243.0 Cells per cubic millimeter | Standard Deviation 233.24 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Baseline (Day 1) | 514.1 Cells per cubic millimeter | Standard Deviation 240.88 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 48 | 190.6 Cells per cubic millimeter | Standard Deviation 180.19 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Change From Baseline in CD4+ Cell Counts at Weeks 24 and 48 | Change from Baseline to Week 24 | 198.5 Cells per cubic millimeter | Standard Deviation 285 |
Secondary
Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48
Plasma samples were collected for quantitative analysis of HIV-1 RNA. log10 values for plasma HIV-1 RNA have been presented. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1) and at Weeks 24 and 48
Population: The analysis was performed on the ITT-E population which included all randomized participants who received at least one dose of study intervention. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.351 Log 10 copies per milliliter | Standard Deviation 0.5712 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 48 | -2.675 Log 10 copies per milliliter | Standard Deviation 0.564 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 24 | -2.718 Log 10 copies per milliliter | Standard Deviation 0.5501 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.353 Log 10 copies per milliliter | Standard Deviation 0.6705 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 48 | -2.762 Log 10 copies per milliliter | Standard Deviation 0.6784 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 24 | -2.784 Log 10 copies per milliliter | Standard Deviation 0.6615 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 24 | -2.565 Log 10 copies per milliliter | Standard Deviation 0.6513 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.165 Log 10 copies per milliliter | Standard Deviation 0.6505 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 48 | -2.580 Log 10 copies per milliliter | Standard Deviation 0.6941 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Baseline (Day 1) | 4.247 Log 10 copies per milliliter | Standard Deviation 0.6765 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 48 | -2.717 Log 10 copies per milliliter | Standard Deviation 0.6672 |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Change From Baseline in Plasma HIV-1 RNA at Weeks 24 and 48 | Change from Baseline to Week 24 | -2.629 Log 10 copies per milliliter | Standard Deviation 0.6835 |
Secondary
Maximum Observed Concentration (Cmax) of GSK3640254 at Steady State
Blood samples were collected at indicated time points for PK analysis of GSK3640254.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2
Population: The analysis was performed on the Intensive PK Population. Only those participants who received GSK3640254 have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Maximum Observed Concentration (Cmax) of GSK3640254 at Steady State | 929.8 ng/mL | Geometric Coefficient of Variation 45.9 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Maximum Observed Concentration (Cmax) of GSK3640254 at Steady State | 1337.3 ng/mL | Geometric Coefficient of Variation 47.7 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Maximum Observed Concentration (Cmax) of GSK3640254 at Steady State | 2094.5 ng/mL | Geometric Coefficient of Variation 39.2 |
Secondary
Number of Participants With Adverse Events (AEs) Leading to Treatment Discontinuation
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants who discontinued study treatment due to AEs are presented.
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 922)
Population: The analysis was performed on the Safety Population, which included all randomized participants who were exposed to study intervention with the exception of any participants with documented evidence of not having consumed any amount of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Adverse Events (AEs) Leading to Treatment Discontinuation | 2 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Adverse Events (AEs) Leading to Treatment Discontinuation | 4 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Adverse Events (AEs) Leading to Treatment Discontinuation | 5 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Adverse Events (AEs) Leading to Treatment Discontinuation | 2 Participants |
Secondary
Number of Participants With AEs Based on Maximum Severity Grades
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The severity of AEs was defined as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.1 and was categorized into grades as following: Grade 1 - mild, Grade 2 - moderate, Grade 3 - severe, Grade 4 - Potentially life threatening and Grade 5 - Fatal. Higher grade indicates more severe condition.
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 922)
Population: The analysis was performed on the Safety Population, which included all randomized participants who were exposed to study intervention with the exception of any participants with documented evidence of not having consumed any amount of study intervention. The data presented here is not cumulative data but the number of participants experiencing the adverse event based on maximum grade at the indicated timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 5 | 0 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 1 | 12 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 2 | 19 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 3 | 5 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 4 | 1 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 2 | 17 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 3 | 5 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 1 | 14 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 4 | 2 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 5 | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 1 | 17 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 2 | 17 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 5 | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 3 | 3 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 4 | 1 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 3 | 3 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 2 | 10 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 1 | 15 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 4 | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs Based on Maximum Severity Grades | Grade 5 | 0 Participants |
Secondary
Number of Participants With AEs of Special Interest (AESI)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with AESI (gastrointestinal (GI), nervous system, and psychiatric AEs) are presented.
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 922)
Population: The analysis was performed on the Safety Population, which included all randomized participants who were exposed to study intervention with the exception of any participants with documented evidence of not having consumed any amount of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Gastrointestinal) | 15 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Psychiatric) | 4 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Nervous system) | 7 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Gastrointestinal) | 18 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Psychiatric) | 3 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Nervous system) | 5 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Nervous system) | 7 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Gastrointestinal) | 14 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Psychiatric) | 4 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Gastrointestinal) | 14 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Psychiatric) | 4 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With AEs of Special Interest (AESI) | AESI (Nervous system) | 3 Participants |
Secondary
Number of Participants With Genotypic Resistance
Plasma samples were collected for resistance testing. Genotypic testing was conducted in participants meeting protocol-defined virologic failure (PDVF) criteria. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only those participants with data available at specified time points have been analyzed.
Time frame: Baseline (Day 1) and at Weeks 24 and 48
Population: The analysis was performed on the PDVF Population, which included participants with A. virologic non-response (Decrease from Baseline \[Day 1\] in plasma HIV-1 RNA of ˂1.0 log10 c/mL unless plasma HIV-1 RNA is \<200 c/mL by Week 12; confirmed plasma HIV-1 RNA levels ≥200 c/mL at or after Week 24; plasma HIV-1 RNA ≥50 c/mL on repeat testing of Week 24 results and prior to Week 28) and B. virologic rebound (confirmed plasma HIV-1 RNA ≥200 c/mL after confirmed consecutive plasma HIV-1 RNA \<50 c/mL).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Baseline (Day 1) | 0 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 48 | 0 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 24 | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Baseline (Day 1) | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 48 | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 24 | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 24 | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Baseline (Day 1) | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 48 | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Baseline (Day 1) | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 48 | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Genotypic Resistance | Weeks 24 | 0 Participants |
Secondary
Number of Participants With Phenotypic Resistance
Plasma samples were collected for resistance testing. Phenotypic testing was conducted in participants meeting PDVF criteria. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Day 1) and at Weeks 24 and 48
Population: The analysis was performed on the PDVF Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Baseline (Day 1) | 0 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 48 | 0 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 24 | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Baseline (Day 1) | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 48 | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 24 | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 24 | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Baseline (Day 1) | 0 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 48 | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Baseline (Day 1) | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 48 | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Phenotypic Resistance | Weeks 24 | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Deaths
An SAE was defined as any serious adverse event that, at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or any other situation according to medical or scientific judgment.
Time frame: From Day 1 up to end of continued access to treatment post-study termination (Day 922)
Population: The analysis was performed on the Safety Population, which included all randomized participants who were exposed to study intervention with the exception of any participants with documented evidence of not having consumed any amount of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Serious Adverse Events | 2 Participants |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Deaths | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Deaths | 0 Participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Serious Adverse Events | 7 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Serious Adverse Events | 2 Participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Deaths | 0 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Serious Adverse Events | 2 Participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Number of Participants With Serious Adverse Events (SAEs) and Deaths | Deaths | 0 Participants |
Secondary
Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Week 2
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254. Observed plasma concentration at the end of the dosing interval was determined directly from the concentration-time data.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2
Population: The analysis was performed on the Intensive PK Population, which included all participants who received at least one dose of GSK3640254, had evaluable drug concentrations reported and where samples were collected according to the intensive PK sampling scheme. Only those participants who received GSK3640254 have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Week 2 | 430.5361 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 56.5 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Week 2 | 604.8387 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 44.2 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Week 2 | 805.2209 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 43.7 |
Secondary
Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254. Observed plasma concentration at the end of the dosing interval was determined directly from the concentration-time data.
Time frame: At Weeks 24 and 48
Population: The analysis was performed on the Sparse PK Population, which included all participants who received at least one dose of GSK3640254, had evaluable drug concentrations reported and had samples collected according to the sparse PK sampling scheme. Only those participants who received GSK3640254 and had data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | Week 24 | 396.5117 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 62.5 |
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | Week 48 | 310.9877 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 135.4 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | Week 24 | 519.6041 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 84.9 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | Week 48 | 568.0656 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 13.4 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | Week 24 | 922.9638 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 51.6 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Plasma Concentration at the End of the Dosing Interval (Ctau) of GSK3640254 at Steady State - Weeks 24 and 48 | Week 48 | 812.4745 Nanogram/ milliliter (ng/mL) | Geometric Coefficient of Variation 49.1 |
Secondary
Observed Pre-dose Plasma Concentration (C0) of GSK3640254 at Steady State
Blood samples were collected at indicated time points for PK analysis of GSK3640254. Observed pre-dose plasma concentration was determined directly from the concentration-time data.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2
Population: The analysis was performed on the Intensive PK Population. Only those participants who received GSK3640254 have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Pre-dose Plasma Concentration (C0) of GSK3640254 at Steady State | 435.9 ng/mL | Geometric Coefficient of Variation 54.6 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Observed Pre-dose Plasma Concentration (C0) of GSK3640254 at Steady State | 603.2 ng/mL | Geometric Coefficient of Variation 59.5 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Observed Pre-dose Plasma Concentration (C0) of GSK3640254 at Steady State | 865.2 ng/mL | Geometric Coefficient of Variation 43.4 |
Secondary
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48
Percentage of participants with plasma HIV-1 RNA \<50 c/mL at week 48 was assessed using the FDA snapshot algorithm to demonstrate the antiviral activity of GSK3640254 given in combination with either ABC/3TC or FTC/TAF compared to the reference treatment of DTG given in combination with either ABC/3TC or FTC/TAF.
Time frame: At Week 48
Population: The analysis was performed on the ITT-E population which included all randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 | 85.0 Percentage of participants |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 | 83.7 Percentage of participants |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 | 76.2 Percentage of participants |
| Dolutegravir (DTG) 50 mg + ABC/3TC or FTC/TAF | Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 | 77.8 Percentage of participants |
Secondary
Steady State Oral Clearance (CLt/F) of GSK3640254
Blood samples were collected at indicated time points for PK analysis of GSK3640254.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2
Population: The analysis was performed on the Intensive PK Population. Only those participants who received GSK3640254 and had data available at specified time points have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Steady State Oral Clearance (CLt/F) of GSK3640254 | 6.6686 Liter/ hour | Geometric Coefficient of Variation 49.8 |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Steady State Oral Clearance (CLt/F) of GSK3640254 | 7.0714 Liter/ hour | Geometric Coefficient of Variation 44.5 |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Steady State Oral Clearance (CLt/F) of GSK3640254 | 6.5129 Liter/ hour | Geometric Coefficient of Variation 40.1 |
Secondary
Time to Cmax (Tmax) of GSK3640254 at Steady State
Blood samples were collected at indicated time points for PK analysis of GSK3640254. Tmax was determined directly from the concentration-time data.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 10, and 24 hours post-dose at Week 2
Population: The analysis was performed on the Intensive PK Population. Only those participants who received GSK3640254 have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3640254 100 mg+ Placebo+ ABC/3TC or FTC/TAF | Time to Cmax (Tmax) of GSK3640254 at Steady State | 3.0000 Hour |
| GSK3640254 150 mg + ABC/3TC or FTC/TAF | Time to Cmax (Tmax) of GSK3640254 at Steady State | 3.4167 Hour |
| GSK3640254 200 mg+ Placebo+ ABC/3TC or FTC/TAF | Time to Cmax (Tmax) of GSK3640254 at Steady State | 3.4583 Hour |