Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024)
Condition: HIV-1 Infection
Intervention: Doravirine, Tenofovir, Lamivudine; Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor; Baseline regimen of cobicistat-boosted elvitegravir; Baseline regimen of a non-nucleoside reverse transcriptase inhibitor; Baseline regimen of two nucleoside reverse transcriptase inhibitors
Intervention description: Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg; Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) administered according to the product circular; Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular; Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular; Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
Intervention MeSH terms: Ritonavir; HIV Protease Inhibitors; Tenofovir; Lamivudine; Cobicistat; Elvitegravir; Reverse Transcriptase Inhibitors; Protease Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 673.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The multicenter, open label, randomized study will evaluate the safety and efficacy of a
      switch to MK-1439A (MK-1439 [doravirine] plus lamivudine and tenofovir disoproxil fumarate)
      in HIV-1-infected participants virologically suppressed on a protocol-specified
      antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir,
      lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as
      assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) <50
      copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age on the day of signing the informed consent.

          -  Understand the study procedures and voluntarily agree to participate by giving written
             informed consent for the trial.

          -  Have plasma HIV-1 RNA levels below the limit of quantification (BLoQ) (<40 copies/mL
             by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the
             screening visit.

          -  Receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted protease
             inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or
             a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2
             NRTIs (and no other antiretroviral therapy) continuously for >= 6 months.

          -  Receiving first or second retroviral regimen (participants receiving a NNRTI at
             Screening must be on their first retroviral regimen)

          -  No history of using an experimental NNRTI

          -  Has a genotype prior to starting his/her initial antiretroviral regimen and no known
             resistance to any of the study agents

          -  Not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at
             the time of enrollment

          -  Has the following laboratory values at screening within 30 days prior to the treatment
             phase of this study: Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN), Serum
             aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 5.0 x ULN,
             and Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male)

          -  Has a calculated creatinine clearance at the time of screening ≥ 50 mL/min, based on
             the Cockcroft-Gault equation

          -  Male or female participant not of reproductive potential or, if of reproductive
             potential, agrees to avoid becoming pregnant or impregnating a partner while receiving
             study drug and for 14 days after the last dose of study drug by complying with one of
             the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable
             contraception during heterosexual activity

          -  For inclusion in Study Extension 1 (optional): completed the Week 48 visit; considered
             to have derived benefit from study participation up to Week 48; considered to be a
             clinically appropriate candidate for an additional 2 years treatment with study drug

          -  For inclusion in Study Extension 2 (optional): completed the Week 144 visit;
             considered to have derived benefit from study participation up to Week 144; considered
             to be a clinically appropriate candidate for an additional 2 years treatment with
             study drug

        Exclusion Criteria:

          -  Uses recreational or illicit drugs or has a recent history of drug or alcohol abuse or
             dependence

          -  Received treatment for a viral infection other than HIV-1, such as hepatitis B, with
             an agent that is active against HIV-1 such as adefovir, emtricitabine, lamivudine, or
             tenofovir

          -  Has documented or known resistance to study drugs including doravirine, lamivudine,
             and/or tenofovir

          -  Participated in a study with an investigational compound or device within 30 days or
             anticipates doing so during the course of this study

          -  Used systemic immunosuppressive therapy or immune modulators within 30 days or
             anticipates needing them during the course of this study (short courses of
             corticosteroids will be allowed)

          -  Current, active diagnosis of acute hepatitis due to any cause (participants with
             chronic hepatitis B and C may enter the study as long as they fulfill all entry
             criteria, have stable liver function tests, and have no significant impairment of
             hepatic function)

          -  Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh
             Class C score or Pugh-Turcotte score >9

          -  Pregnant, breastfeeding, or expecting to conceive at any time during the study

          -  Female and is expecting to donate eggs or male and is expecting to donate sperm during
             the study