Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF
Condition: HIV-1 Infection
Intervention: FTC/TDF; F/TAF; Allowed third antiretroviral agent; FTC/TDF Placebo; F/TAF Placebo
Intervention description: 200/300 mg FDC tablets administered orally once daily; Tablets administered orally once daily; An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted lopinavir (LPV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV; Sustiva®), rilpivirine (RPV; Edurant®), nevirapine (NVP;Viramune®), raltegravir (RAL; Isentress®), dolutegravir (DTG;Tivicay®), and maraviroc (MVC; Selzentry®).; Tablets administered orally once daily; Tablets administered orally once daily
Intervention MeSH terms: Anti-Retroviral Agents
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 668.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HIV-1 Positive; Virologically-suppressed

Summary:

      This study will evaluate the efficacy of switching from emtricitabine/tenofovir disoproxil
      fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide
      (F/TAF) FDC in HIV-1 positive participants who are virologically suppressed on regimens
      containing FTC/TDF.

      This study will consist of a 96 week double-blind treatment period. After Week 96, all
      participants will continue on blinded study drug treatment and attend visits every 12 weeks
      until treatment assignments are unblinded. All participants will return for an unblinding
      visit and will be given the option to receive open-label F/TAF and attend visits every 12
      weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical
      development program.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Ability to understand and sign a written informed consent form, which must be obtained
             prior to initiation of study procedures

          -  Currently receiving antiretroviral regimen containing FTC/TDF in combination with one
             third agent for ≥ 6 consecutive months prior to screening.

          -  Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months preceding the screening
             visit (measured at least twice using the same assay) and not experienced two
             consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two
             consecutive) HIV-1 RNA below detectable levels on the current regimen in the past
             year.

          -  Plasma HIV-1 RNA should be < 50 copies/mL at the screening visit.

          -  Normal electrocardiogram (ECG)

          -  Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the
             Cockcroft-Gault formula for creatinine clearance

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper
             limit of the normal range (ULN)

          -  Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented
             Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total
             bilirubin up to 5 x ULN)

          -  Adequate hematologic function

          -  Serum amylase ≤ 5 × ULN

          -  Females of childbearing potential must agree to utilize highly effective contraception
             methods or be non-heterosexually active, or practice abstinence from screening
             throughout the duration of the study treatment and for 30 days following the last dose
             of the study drug.

          -  Females who have stopped menstruating for ≥ 12 months but do not have documentation of
             ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at
             screening within the post-menopausal range based on the Central Laboratory reference
             range.

          -  Females 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.

          -  Males 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.

        Key Exclusion Criteria:

          -  A new AIDS-defining condition diagnosed within the 30 days prior to screening

          -  Hepatitis C virus (HCV) antibody positive and HCV RNA detectable

          -  Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)

          -  Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg,
             osteoporosis)

          -  Females who are breastfeeding

          -  Positive serum pregnancy test

          -  Have an implanted defibrillator or pacemaker

          -  Current alcohol or substance use judged by the investigator to potentially interfere
             with study compliance

          -  A history of malignancy within the past 5 years (prior to screening) 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

          -  Individuals receiving ongoing therapy with any of the medications not to be used with
             FTC, TAF, TDF or other antiretroviral third agents.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.