Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: Etravirine (Intelence); Truvada
Intervention description: Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day; Etravirine 400 mg (four 100 mg or two 200 mg tablets) taken orally once a day with one pill of Truvada (200 mg of emtricitabine and 300 mg of tenofovir) taken orally once a day
Intervention MeSH terms: Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Etravirine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; Infection; Treatment Naive; Adults; Once; Daily; Etravirine; HIV-1 Infection

Summary:

      The main study is a single arm, open-label, prospective study to assess antiretroviral
      activity and tolerability of etravirine (TMC-125) 400 mg once daily, given with fixed-dose
      tenofovir/emtricitabine, in treatment-naïve HIV-1-infected men and women. There are also a
      genital secretions pharmacokinetic (PK) sub-study and a metabolic sub-study. The purpose of
      the genital secretions PK sub-study is to gain information about drug levels and HIV-1 RNA in
      genital secretions when subjects are taking etravirine. The purpose of the metabolic
      sub-study is to learn about the effects of etravirine on body composition, as well as lipid
      and glucose levels.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection as documented by any licensed ELISA test and confirmed by Western Blot
             or other confirmatory test at any time prior to study entry. Acceptable alternative
             confirmatory tests are plasma HIV-1 RNA, HIV-1 culture, HIV-1 antigen, or a second
             antibody test by a method other than ELISA. Alternatively, if an HIV-antibody test
             result is not available, two HIV-1 RNA values >2000 copies/mL, drawn at least 24 hours
             apart, performed by any laboratory that has clinical laboratory improvement amendments
             (CLIA) certification, or its equivalent, may be used to document infection.

          -  Age 18 years or older.

          -  Able to provide informed consent.

          -  In the opinion of the investigator, able to comply with study medication and
             procedures.

          -  Plasma HIV-1 RNA ≥ 1000 copies/mL as measured by any FDA-approved test for quantifying
             HIV-1 RNA within 90 days prior to study entry.

          -  Less than or equal to 10 days of cumulative exposure to antiretroviral therapy.

          -  For all women of reproductive potential, a negative urine or serum β-human chorionic
             gonadotropin (β-HCG) pregnancy test performed within 48 hours prior to study entry.

               -  All study volunteers, both male and female, must agree not to participate in a
                  conception process (i.e., active attempt to become pregnant or to impregnate,
                  sperm donation, in vitro fertilization) while receiving study medications and for
                  6 weeks after stopping study medications.

               -  If participating in sexual activity that could lead to conception, study
                  volunteers must agree to use at least one method of reliable contraception which
                  must be a barrier method (i.e., a condom without spermicide, a diaphragm, or
                  cervical cap) throughout the study and for 6 weeks thereafter.

        NOTE: Acceptable documentation of lack of reproductive potential for a woman is
        self-reported history of being postmenopausal for at least 24 months, or having had
        surgical sterilization (hysterectomy, or bilateral oophorectomy, or bilateral tubal
        ligation) or of male partner's azoospermia. Acceptable documentation for a man is
        self-reported history of azoospermia.

          -  Hemoglobin ≥ 7.5 g/dL within 45 days prior to study entry.

          -  Absolute neutrophil count ≥ 500/mm³ within 45 days prior to study entry.

          -  Platelets ≥ 50,000/mm³ within 45 days prior to study entry.

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3X upper limit of
             normal (ULN) or bilirubin ≤ 2.5 ULN within 45 days prior to study entry.

          -  Glomerular filtration rate (GFR) > 59 as calculated by Modification of Diet in Renal
             Disease (MDRD) equation within 45 days prior to study entry.

        Exclusion Criteria:

          -  Prior receipt of etravirine, dapivirine, or rilpivirine (Edurant), or Complera.

          -  Evidence of any of the resistance-associated mutations listed below on genotype
             testing performed within 90 days of study entry. Any pending resistance testing
             ordered prior to study entry must be available for review by the investigator prior to
             enrollment. Major resistance mutations include:

               1. Any of the following nonnucleoside reverse transcriptase inhibitor (NNRTI)
                  mutations: V90I, A98G, L100I, K101E/H/P/Q, K103H/S/T, V106A/I/M, V108I,
                  E138A/G/K/Q, V179D/E/F/G/I/T, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y,
                  P225H, F227C/L, M230I/L, P236L, K238N/T, K103N.

               2. Any of the following NRTI mutations: M184V/I, K70E/R, K65R, M41L, 69 insert,
                  L210W, T215Y/F, K219Q/E, L74V.

          -  Pregnancy

          -  Breastfeeding

          -  Any condition which, in the opinion of the investigator, would be likely to interfere
             with ability to take the study medications appropriately and comply with the study
             protocol.

          -  Use of any systemic antineoplastic or immunomodulatory treatment, systemic
             corticosteroids, investigational vaccines, interleukins, interferons, growth factors,
             or intravenous immunoglobulin (IVIG) within 30 days prior to study entry.

        NOTE: Routine standard of care, including hepatitis B, influenza, pneumococcus, and tetanus
        vaccines are permitted.

          -  Current active illness requiring systemic treatment and/or hospitalization until the
             individual completes therapy or, in the opinion of the investigator, is clinically
             stable on therapy for at least 7 days prior to study entry.

          -  Life expectancy of less than 6 months.

          -  Acute viral hepatitis.

          -  Known allergy/hypersensitivity to components of the study drugs or their formulations.

          -  Use of any medications that are prohibited during the study period (see Section 8.1 of
             the protocol - Prohibited Medications).

          -  Refusal by an individual who is taking anti-depressant medications to allow the
             investigator or Primary HIV Care provider to communicate with his/her
             psychiatrist/Mental Health clinician regarding the initiation of study medications in
             those cases where co-administration of study drugs may alter anti-depressant drug
             levels.