Emtricitabine/Tenofovir Alafenamide as Salvage ART
Condition: HIV
Intervention: FTC/TAF
Intervention description: Tenofovir alafenamide (TAF) is an investigational oral prodrug of tenofovir. This trial will explore the safety and efficacy of TAF in a fixed combination with emtricitabine (FTC) (F/TAF, Gilead Sciences Inc.) as part of a salvage antiretroviral regimen for HIV-1-infected adults and adolescents (greater than or equal to 14 years) who experienced virologic failure.
Intervention MeSH terms: Tenofovir; Emtricitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 14 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: TAF; F/TAF; antiretroviral therapy; TDF; directly observed therapy

Summary:

      Background:

      HIV attacks the immune system. Antiretroviral therapy (ART) is a combination of drugs used
      for treating HIV infection. For some people, ART drugs stop working against their HIV.
      Researchers want to see if a different form of the drug tenofovir (an ART drug currently
      approved by the FDA), combined with another drug, may help people whose HIV is resistant to
      ART. This combination pill is called F/TAF

      Objective:

      To study the safety and efficacy of the drug F/TAF, when used with other ART, for people
      whose HIV infection has been hard to control with available medicines.

      Eligibility:

      People age 14 years and older who have HIV infection and are enrolled in the DOTCOM
      (14-I-0009) protocol.

      Design:

      Participants will be screened with physical exam, medical history, and blood and urine tests.

      Participants will stay in the hospital for at least 10 days. For the first 9 days, they will
      take F/TAF by mouth along with their usual ART drugs.

      In the hospital, they will repeat the screening tests.

      Participants will have a DEXA scan, an x-ray that measures calcium and other minerals in the
      bones. Participants will lie on a soft table while the scanner passes over the lower spine
      and hips.

      Participants will get a supply of F/TAF and some new ART drugs to take at home.

      Participants will have follow-up visits in 1, 2, 4, 8, and 12 weeks. After the 12-week visit,
      they will come back about every 3 months for about 1 year.

      At these visits, participants will repeat the screening tests. They will discuss any problems
      taking their ART drugs. They may have another DEXA scan.
    

Eligibility criteria:

        INCLUSION

          -  Age greater than or equal to 14 years

          -  Documented HIV-1 infection (written documentation of positive standard ELISA or rapid
             HIV-1/HIV-2 antibody test with confirmatory Western Blot, or documentation of repeated
             HIV RNA of > 1,000 copies/mL)

          -  Concurrent enrollment in the DOTCOM (14-I-0009) protocol

          -  For females of childbearing potential, willingness to use effective contraception for
             the duration of the study

          -  Willingness to be hospitalized for 10-15 days (with potential for day passes)

          -  Willingness to have blood samples stored for future research that may include genetic
             testing

          -  Multiple ART failure as defined by at least one of the following criteria:

               -  HIV RNA > 1000 copies/mL and documented virologic failure on at least 1 prior ART
                  regimen and at least 2 consecutive HIV RNA plasma measurements of > 1,000
                  copies/mL, including the last documented value, while on the currently prescribed
                  ART regimen for at least 6 months; or

               -  Documented extensive resistance to at least 3 antiretroviral (ARV) drug classes,
                  and persistent plasma viremia (HIV RNA > 1,000 copies/mL for > 6 months) despite
                  multiple regimen changes. The patient may be enrolled even if they have been
                  prescribed their current regimens for less than 6 months.

          -  Where neither TDF nor ABC are optimal NRTI options as defined by at least one of the
             following criteria:

               -  Presence of the M184V mutation plus TDF-associated resistance mutations based on
                  genotypic/phenotypic testing, specifically K65R alone, or with TAMs (such as 41L,
                  67N, 70R, 210W, 215Y/F, or 219Q/E) with or without other NRTI-associated
                  mutations; or

               -  FTC/TDF is not considered an option due to impaired renal function (eGFR by
                  Cockroft-Gault equation [eGFR(CG)]=30-60 mL/min), or risk of renal impairment
                  because of conditions such as uncontrolled hypertension, diabetes mellitus, or
                  history of renal toxicity while receiving a TDF-based regimen; and where ABC/3TC
                  is contraindicated (ie, presence of HLA B*5701 allele or history of
                  hypersensitivity reaction to ABC), or is a suboptimal option (eg, presence of
                  ABC-associated resistance mutation(s) or in patients with HBV co-infection).

        EXCLUSION

          -  Severe renal impairment (eGFR(CG) <30 mL/min)

          -  Acute medical illness stemming from a significant co-morbidity (eg, malignancy
             requiring chemotherapy, treatment of an acute opportunistic infection or acute renal
             failture). Enrollment may be deferred up to 3 months to allow a condition to resolve
             or stabilize.

          -  Pregnancy; however if a patient becomes pregnant while enrolled in the protocol, she
             may continue participation throughout her pregnancy.

          -  Breastfeeding

          -  Concomitant use of one of the following medications: carbamazepine, oxcarbazepine,
             phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bisphosphonate, St. John s
             wort, echinacea, milk thistle, sho-saiko-to, and probenecid.

          -  Any illness or condition that, in the investigator's opinion, may substantially
             increase the risk of participation in the study, or compromise the scientific
             objectives.