Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011)
Condition: HIV-1 Infection
Intervention: Islatravir; Placebo to Islatravir; Doravirine; Placebo to Doravirine; Lamivudine; Placebo to Lamivudine; Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate; Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate; Doravirine/Islatravir
Intervention description: Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.; Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks; Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks; Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks; Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks; Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks; Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.; Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks; Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
Intervention MeSH terms: Tenofovir; Lamivudine; Islatravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Masking in Part 1, including matching placebo. Masking only to dose in Part 2. No masking in Parts 3 and 4.
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the safety, tolerability, antiretroviral activity, and
      pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and
      lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human
      immunodeficiency virus type 1 (HIV-1) infection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has HIV-1 infection

          -  Is naïve to anti-retroviral therapy (ART).

          -  Is clinically stable, with no signs or symptoms of acute infection, at the time of
             entry into the study

          -  Female is not pregnant, not breastfeeding, not a woman of childbearing potential
             (WOCBP); but if WOCBP agrees to follow the contraceptive guidance

          -  All participants, male and female, agree to use barrier methods of contraception when
             engaged in any sexual activity during treatment and for 6 weeks following treatment.

        Exclusion Criteria:

          -  Is a user of recreational or illicit drugs or has had a history of drug or alcohol
             abuse or dependence that may interfere with trial participation

          -  Has significant hypersensitivity or other contraindication to any of the components of
             the study drugs

          -  Has a history of malignancy ≤5 years prior

          -  Female expects to donate eggs at any time during the study

          -  Is breastfeeding or expecting to conceive

          -  A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of
             study treatment

          -  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 used systemic immunosuppressive therapy or immune modulators within 30 days prior
             to treatment in this study or is anticipated to need them during the course of the
             study

          -  Requires any of the following prohibited medications: Carbamazepine, Phenobarbital,
             Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan,
             Nafcillin, Pentostatin

          -  Is currently participating in or has participated in an interventional clinical trial
             with an investigational compound or device within 30 days of signing informed consent
             to participate in this current trial

          -  Has a documented or known virologic resistance to any approved HIV-1 reverse
             transcriptase inhibitor, protease inhibitor, integrase inhibitor

          -  Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV
             co-infection defined as hepatitis B surface antigen [HBsAg]-positive

          -  Has a current (active) diagnosis of acute hepatitis due to any cause

          -  Has previously been randomized in a study and received islatravir (MK-8591), DOR,
             Doravirine, Tenofovir, Lamivudine, or 3TC.