Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adults Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184I
Condition: HIV-1 Infection
Intervention: E/C/F/TAF
Intervention description: 150/150/200/10 mg FDC tablets administered orally once daily
Intervention MeSH terms: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the efficacy of
      elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose
      combination (FDC) after switching from a stable regimen consisting of emtricitabine/tenofovir
      disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) plus a third antiretroviral
      (ARV) agent in participants harboring the archived nucleoside/nucleotide reverse
      transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in human
      immunodeficiency virus (HIV) -1 reverse transcriptase.

      This is a two part study. If the rate of virologic failure in Part 1 is deemed acceptable,
      once the internal data monitoring committee officially completes the interim review, the
      study will continue to Part 2.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Documented historical genotype report showing mutation M184V and/or M184I (mixtures
             are acceptable) in reverse transcriptase. Individuals must not have any primary
             integrase strand transfer inhibitor (INSTI) or primary protease inhibitor (PI)
             resistance mutations present on historical genotype; non-nucleoside reverse
             transcriptase inhibitor (NNRTI) mutations are allowed.

          -  Proviral deoxyribonucleic acid (DNA) test must not have additional exclusion
             resistance mutations against PIs, NRTIs and INSTIs

               -  Part 1: Historical genotype report must show mutation M184V and/or M184I in
                  reverse transcriptase WITHOUT any other NRTI resistance mutation (including
                  thymidine analogue-associated mutations [TAMs] [TAMs are: M41L, D67N, K70R,
                  L210W, T215Y/F, and K219Q/E/N/R], K65R, K70E, T69 insertion, and Q151M mutation
                  complex [A62V, V75I, F77L, F116Y, Q151M])

               -  Part 2 (after the interim efficacy review): Historical genotype report must show
                  M184V and/or M184I in reverse transcriptase WITH or WITHOUT 1 or 2 TAMs. Evidence
                  of K65R, K70E, T69 insertion and/or Q151M mutation complex will not be eligible

          -  Currently receiving an ARV regimen consisting of FTC/TDF or ABC/3TC in combination
             with one third ARV agent for ≥ 6 consecutive months preceding the screening visit

          -  Documented plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL for ≥ 6 months
             preceding the screening visit

          -  Plasma HIV-1 RNA levels < 50 copies/mL at screening visit

          -  Estimated glomerular filtration rate (GFR) ≥ 30 mL/min according to the
             Cockcroft-Gault formula for creatinine clearance

          -  A female individual is eligible to enter the study if it is confirmed that she is:

               -  not pregnant

               -  of non-childbearing potential

               -  stopped menstruating for ≥ 12 months

               -  of childbearing potential and agrees to utilize the protocol-specified method of
                  contraception or be non-heterosexually active or practice sexual abstinence from
                  screening throughout the duration of study treatment and for 30 days following
                  discontinuation of study drugs

          -  Male individuals must agree to use the protocol-specified method(s) of contraception
             during heterosexual intercourse or be non-heterosexually active, or practice sexual
             abstinence from screening 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:

          -  Individuals will have no evidence of previous virologic failure on a PI/r or
             INSTI-based regimen (with or without resistance to either class of ARV). Individuals
             may have evidence of prior virologic failure on only an NNRTI plus 2 NRTI-based
             regimen

          -  Individuals on a current PI/r-based regimen will have no evidence of previous use of
             any approved or experimental integrase strand transfer inhibitor (INSTI) (for any
             length of time)

          -  Hepatitis C infection that would require therapy during the study

          -  Hepatitis B surface antigen (HBsAg) positive

          -  Individuals with clinical evidence of decompensated cirrhosis (eg, ascites,
             encephalopathy, variceal bleeding)

          -  Have an implanted defibrillator or pacemaker

          -  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. Individuals with cutaneous KS are
             eligible, but must not have received any systemic therapy for KS within 30 days of Day
             1 and must not be anticipated to require systemic therapy during the study

          -  Active, serious infections (other than HIV-1 infection) requiring parenteral
             antibiotic or antifungal therapy within 30 days prior to Day 1

        NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.