Doravirine/Islatravir (DOR/ISL) in Pediatric Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are <18 Years of Age and Weigh ≥35 kg (MK-8591A-028)
Condition: HIV-1 Infection
MeSH terms: Infections
Intervention: DOR/ISL
Intervention description: 100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.
Intervention MeSH terms: Islatravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      This is a phase 2, single-group, multi-site, open-label study of an islatravir/doravirine
      (ISL/DOR, MK-8591A) fixed dose combination (FDC) for the treatment of human immunodeficiency
      virus type 1 (HIV-1) infection in pediatric participants who are virologically suppressed
      (VS) on antiretroviral therapy (ART) for ≥3 months or are treatment-naive (TN). The primary
      purposes of the study are 1) to examine the steady-state pharmacokinetics (PK) of ISL in
      plasma; 2) the steady-state PK of ISL-triphosphate (ISL-TP) in peripheral blood mononuclear
      cells (PBMCs); and 3) to examine the safety and tolerability of ISL/DOR.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is HIV-1 positive, is <18 years of age, and weighs ≥35 kg at screening.

          -  VS Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA <50 copies/mL
             and has been receiving continuous, stable oral 2-drug or 3-drug combination ART ± PK
             booster with documented viral suppression for ≥3 months prior to providing documented
             informed consent/assent and has no history of prior virologic treatment failure on any
             past or current regimen.

          -  TN Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA ≥500 copies/mL
             and is naive to ART defined as having received <=10 days of prior therapy with any
             antiretrovirals following HIV-1 diagnosis other than pre-exposure prophylaxis (PrEP)
             or potentially exposed person (PEP).

          -  If female, is not pregnant or breastfeeding, and is either 1) not a woman of
             childbearing potential (WOCBP) or 2) is a WOCBP and is using acceptable contraception
             or is abstinent.

        Exclusion Criteria:

          -  Has HIV-2 infection.

          -  Has hypersensitivity or other contraindication to any of the components of the study
             drugs as determined by the investigator.

          -  Has an active diagnosis of hepatitis due to any cause, including active hepatitis B
             virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV
             deoxyribonucleic acid [DNA] positive).

          -  Has a history of malignancy ≤5 years prior to providing documented informed consent
             except for adequately treated basal cell or squamous cell skin cancer, in situ
             cervical cancer, or cutaneous Kaposi's sarcoma.

          -  Has a history or current evidence of any condition (including active tuberculosis
             infection), therapy, laboratory abnormality or other circumstance (including drug or
             alcohol use or dependence) that might, in the opinion of the investigator, confound
             the results of the study or interfere with the participant's participation for the
             full duration of the study, such that it is not in the best interest of the
             participant to participate.

          -  Is taking or is anticipated to require systemic immunosuppressive therapy, immune
             modulators, or any prohibited therapies from 45 days prior to Day 1 through the study
             treatment period.

          -  Is currently taking long-acting cabotegravir-rilpivirine.

          -  Is currently participating in or has participated in an interventional clinical study
             with an investigational compound or device from 45 days prior to Day 1 through the
             study treatment period.

          -  Has a documented or known virologic resistance to DOR/ISL (DOR resistance
             substitutions in reverse transcriptase: V106A/M, V108I, Y188L, H221Y, P225H, F227C/L,
             M230I/L, L234I, P236L, or Y318F; ISL resistance substitution in reverse transcriptase:
             M184V/I).

          -  Has exclusionary laboratory values.

          -  Is female and expecting to conceive or donate eggs at any time during the study.