A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: GSK3640254; Dolutegravir; Lamivudine capsules; Lamivudine tablets
Intervention description: GSK3640254 was available as 25 mg or 100 mg tablets administered orally.; DTG was available as 50 mg tablets administered orally.; 3TC was available as 300 mg capsules administered orally as a blinded treatment.; 3TC was available as 300 mg tablets administered orally as an unblinded treatment.
Intervention MeSH terms: Lamivudine; Dolutegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a randomized, parallel-group study.
Masking: Double (Participant, Investigator)
Masking description: 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 through the Week 24 primary endpoint.
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Human immunodeficiency virus-1; GSK3640254; Dolutegravir; Lamivudine; Treatment-naive

Summary:

      The purpose of this study was to evaluate the efficacy of GSK3640254 + DTG relative to
      lamivudine (3TC) + DTG in treatment-naïve adult participants living with human
      immunodeficiency virus (HIV)-1. The participants were randomized to one of the three doses of
      blinded GSK3640254 (100, 150, or 200 milligrams [mgs]) or a reference arm of blinded 3TC-each
      in combination with open label DTG.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy)
             received after a known diagnosis of HIV-1 infection.

          -  Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to
             (>=)1000 c/mL.

          -  Screening CD4+ T-cell count >=250 cells per millimeter^3 (cells/cubic millimeter).

          -  Body weight >=50.0 kilograms (kg) (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs.)
             for women and body mass index (BMI) >18.5 kilograms per meter^2 (kg/meter square).
             Calculations will utilize sex assigned at birth.

        Exclusion Criteria:

          -  Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3
             disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy.

          -  Presence of primary HIV infection, evidenced by acute retroviral syndrome (example
             [e.g.], fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months)
             documented viremia without antibody production and/or evidence of recent (within 3
             months) documented seroconversion.

          -  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.

          -  Any history of significant underlying psychiatric disorder.

          -  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.

          -  A pre-existing condition, in the opinion of the Investigator or 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 interventions or render the participant unable to take oral
             study treatment.

          -  Familial or personal history of long QT syndrome or sudden cardiac death.

          -  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).

          -  Participants who require concomitant medications known to be associated with a
             prolonged corrected QT (QTc) interval.

          -  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.