Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
Condition: HIV-1; HIV Infections; Acquired Immunodeficiency Syndrome
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Intervention: E/C/F/TAF; DRV; Baseline DRV- containing ARV regimen
Intervention description: 150/150/200/10 mg FDC tablet administered orally once daily; 800 mg tablet administered orally once daily; Participants will take their baseline DRV- containing ARV regimen as prescribed.
Intervention MeSH terms: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 158.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV-1; HIV; Treatment-Experienced

Summary:

      The primary objective of this study is to evaluate the efficacy of
      elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose
      combination (FDC) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in
      virologically suppressed, HIV-1 positive participants with HIV-1 RNA <50 copies/mL at Week
      24.

      This study consists of 48 weeks of open-label phase followed by an optional Extension Phase
      in which all the participants will receive E/C/F/TAF+DRV.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Ability to understand and sign a written informed consent form

          -  History of at least two prior antiretroviral regimens, and history of resistance to at
             least two different classes of antiretroviral agents

          -  Plasma HIV-1 RNA levels < 50 copies/mL at screening. Virologically suppressed on the
             current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once
             daily continuously for ≥ 4 months preceding the screening visit and have maintained
             documented undetectable plasma HIV-1 RNA levels (< 50 copies/mL) and must have
             documentation of genotype/phenotype prior to current regimen which shows no darunavir
             associated resistance mutation.

          -  Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but
             not twice daily), or have never received integrase inhibitor, or have documentation of
             genotype/phenotype within 12 months prior to current regimen which must show no
             evidence of resistance to integrase inhibitors

          -  Normal ECG

          -  Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft
             Gault formula for creatinine clearance

          -  Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

          -  Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥
             50,000/mm^3; hemoglobin ≥ 8.5 g/dL)

          -  Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible
             if serum lipase is ≤ 5 × ULN)

          -  A female individual is eligible to enter the study if it is confirmed that she is:

               -  Not pregnant or nursing

               -  Of non-childbearing potential (i.e., women who have had a hysterectomy, have had
                  both ovaries removed or medically documented ovarian failure, or are
                  postmenopausal women > 54 years of age with cessation (for ≥ 12 months) of
                  previously occurring menses), or

               -  Of childbearing potential and agrees to utilize highly effective contraception
                  methods or be non-heterosexually active or practice sexual abstinence from
                  screening throughout the duration of study treatment and for 30 days following
                  the last study drug dose.

               -  Female individuals who utilize hormonal contraceptive as one of their birth
                  control methods must have used the same method for at least three months prior to
                  study dosing.

          -  Male individuals must agree to utilize a highly effective method of contraception
             during heterosexual intercourse or be non-heterosexually active, or practice sexual
             abstinence from first dose throughout the study period and for 30 days following the
             last study drug dose.

          -  Male individuals must agree to refrain from sperm donation from first dose until at
             least 30 days after the last study drug dose.

        Key Exclusion Criteria:

          -  A new AIDS-defining condition diagnosed within the 30 days prior to screening (except
             CD4 cell count and/or percentage criteria)

          -  Hepatitis B surface antigen (HBsAg) positive

          -  Individuals receiving drug treatment for Hepatitis C, or individuals who are
             anticipated to receive treatment for Hepatitis C during the course of the study.

          -  Must not have Q151M, T69ins, or > 3 thymidine analogue mutations (TAMS) present on
             documented historic genotype report

          -  Individuals experiencing decompensated cirrhosis

          -  Females who are breastfeeding

          -  Positive serum pregnancy test

          -  Have an implanted defibrillator or pacemaker

          -  Current alcohol or substance use that may interfere with individual's study compliance

          -  A history of malignancy within the past 5 years or ongoing malignancy other than
             cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive
             cutaneous squamous carcinoma.

          -  Active, serious infections (other than HIV-1 infection) requiring parenteral
             antibiotic or antifungal therapy within 30 days prior to Day 1 visit

          -  Any other clinical condition or prior therapy that would make the individual
             unsuitable for the study or unable to comply with dosing requirements

          -  Participation in any other clinical trial (including observational trials) without
             prior approval from the sponsor is prohibited while participating in this trial

          -  Individuals receiving ongoing therapy with any of the disallowed medications,
             including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or
             DRV; or individuals with any known allergies to the study drugs.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.