Effects of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Participants (MK-1439A-028)
Condition: HIV-1; Central Nervous System
Intervention: Doravirine, Tenofovir, Lamivudine - Blinded; Doravirine, Tenofovir, Lamivudine - Open-Label; ATRIPLA^TM; Placebo to ATRIPLA™; Placebo to Doravirine, Tenofovir, Lamivudine
Intervention description: A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded period; A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; also an additional 96 weeks during the Open-Label extension period 1; a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2; and a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3.; A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded period; A single placebo to ATRIPLA™ tablet administered orally, once daily for 12 weeks during the Blinded period; A single placebo to doravirine, tenofovir, lamivudine tablet administered orally, once daily for 12 weeks during the Blinded period
Intervention MeSH terms: Tenofovir; Lamivudine; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study aims to evaluate a switch from fixed dose combination (FDC) treatment with
      ATRIPLA^TM for 12 weeks prior to screening to FDC treatment with Doravirine, Tenofovir,
      Lamivudine (MK-1439A) in virologically-suppressed, human immunodeficiency virus type 1
      (HIV-1)-infected participants. The primary hypothesis is that switching from ATRIPLA^TM to
      Doravirine, Tenofovir, Lamivudine results in a lower proportion of participants with at least
      one CNS toxicity of at least Grade 2 intensity at Week 12 than continuation of ATRIPLA^TM
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  is taking ATRIPLA™, generic versions of ATRIPLA™, or the components of ATRIPLA™
             (EFV,TDF plus emtricitabine),

          -  has documentation of HIV-1 ribonucleic acid (RNA) < 50 copies/mL during the 12 weeks
             prior to screening while on ATRIPLA™.

          -  has plasma HIV-1 RNA levels below the limits of quantification (BLoQ) at the screening
             visit.

          -  if genotyped prior to starting initial antiretroviral regimen, must have no known
             resistance to any of the study agents

          -  has at least one EFV-associated CNS toxicities of Grade 2 or worse intensity both at
             the time of screening and at Study Day 1

          -  is highly unlikely to become pregnant or to impregnate a partner

          -  To be eligible for study extension 1, participants from Immediate Switch Group (ISG)
             must have completed Study Week 24, and benefited from study participation;
             participants from Deferred Switch Group (DSG) must have completed Study Week 36, and
             benefited from study participation as determined by the investigator

          -  To be eligible for study extension 2, participants from ISG must have completed Study
             Week 120, and benefited from study participation; participants from DSG must have
             completed Study Week 132, and benefited from study participation as determined by the
             investigator

        Exclusion Criteria:

          -  is a user of recreational or illicit drugs or has had a recent history of drug or
             alcohol abuse or dependence.

          -  has ongoing Grade 4 CNS toxicity during screening period that requires a prompt change
             in ART

          -  has been treated for a viral infection other than HIV-1, such as hepatitis B, with an
             agent that is active against HIV-1 including, but not limited to, adefovir,
             emtricitabine, entecavir, lamivudine or tenofovir.

          -  has documented or known resistance to study drugs including doravirine, lamivudine,
             and/or tenofovir

          -  has participated in, or anticipates participating in a study with an investigational
             compound/device within 30 days prior to signing informed consent

          -  has used systemic immunosuppressive therapy or immune modulators or anticipates using
             them within 30 days prior to this study

          -  requires or anticipates requiring any of the prohibited medications

          -  has significant hypersensitivity or other contraindication to any of the components of
             the study drugs

          -  has a current (active) diagnosis of acute hepatitis due to any cause.

          -  has evidence of decompensated liver disease manifested by the presence of or a history
             of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other
             signs or symptoms of advanced liver diseases, or has liver cirrhosis and a Child-Pugh
             Class C score or Pugh-Turcotte (CPT) score > 9.

          -  is pregnant, breastfeeding, or expecting to conceive.

          -  female is expecting to donate eggs (at any time during the study) or male is expecting
             to donate sperm (at any time during the study).