Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018)
Condition: HIV-1
Intervention: Doravirine; Darunavir; Ritonavir; TRUVADA™ or EPZICOM™/KIVEXA™
Intervention description: Doravirine 100 mg tablet administered p.o., q.d.; Darunavir 800 mg tablet administered p.o., q.d.; Ritonavir 100 mg tablet administered p.o., q.d.; The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate, p.o., q.d., or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o., q.d.
Intervention MeSH terms: Ritonavir; Darunavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 769.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy
      and safety of doravirine will be determined relative to a protease inhibitor (PI).
      Participants will receive double-blind treatment during the 96-week Base Study. Eligible
      participants in either of the Base Study groups will continue to receive the
      doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1.
      Eligible participants who are deriving benefit will continue in Study Extension 2 to receive
      the doravirine-containing regimen open label until doravirine becomes locally available or
      for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine
      100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in
      combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants
      with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is
      established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir
      (800 mg/100 mg) q.d. will be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is HIV-1 positive and has HIV treatment indicated based on physician assessment.

          -  Has received no (0 days of) antiretroviral therapy (ART), including investigational
             antiretroviral agents.

          -  Is considered clinically stable with no signs or symptoms of active infection for at
             least 2 weeks prior to the start of treatment.

          -  Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate
             a partner because they are not of reproductive potential, or agree to practice
             abstinence or use acceptable contraception for up to 14 days after the last dose of
             study drug.

          -  Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96
             visit, 2) derived benefit from participation through Week 96 in the opinion of the
             investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of
             treatment with the Study Extension regimen.

          -  Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192
             visit, 2) derived benefit from participation through Week 192 in the opinion of the
             investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with
             the Study Extension regimen.

        Exclusion Criteria:

          -  Uses or has had a recent history of using recreational or illicit drugs.

          -  Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an
             agent that is active against HIV-1.

          -  Has documented or known resistance to study drugs including doravirine, darunavir,
             ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.

          -  Has participated in a study with an investigational compound/device within the prior
             month, or anticipates doing so during this study.

          -  Has used systemic immunosuppressive therapy or immune modulators within the prior 30
             days, or anticipates doing so during this study.

          -  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.

          -  Is pregnant, breastfeeding or expecting to conceive at any time during the study.

          -  Female who expects to donate eggs, or male who expects to donate sperm at any time
             during the study.