Safety and Efficacy Study of Switching From Epzicom to Truvada
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); abacavir (ABC)/lamivudine (3TC)
Intervention description: FTC 200 mg/TDF 300 mg tablet, once a day; ABC 600 mg/3TC 300 mg tablet, once a day
Intervention MeSH terms: Tenofovir; Lamivudine; Emtricitabine; Abacavir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 312.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HIV 1

Summary:

      This protocol describes a prospective, randomized, open-label, multicenter study to evaluate
      the safety and efficacy of switching from fixed dose abacavir (ABC)/lamivudine (3TC) to fixed
      dose emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in virologically suppressed,
      human immunodeficiency virus type 1 (HIV-1) infected subjects maintained on a
      ritonavir-boosted protease inhibitor (PI/r)-containing antiretroviral (ARV) regimen. Duration
      of treatment is 48 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult (greater than or equal to 18 years) males or non-pregnant, non-lactating females

          -  HIV-1 infected subjects currently receiving a ritonavir-boosted protease inhibitor and
             fixed-dose ABC/3TC regimen continuously for greater than or equal to 3 months

          -  HIV infection as documented by a validated HIV antibody enzyme-linked immunosorbent
             assay (ELISA) and confirmed by one of the following:

               -  Immunoblot detection of HIV antibody

               -  Positive HIV-1 blood culture

               -  Positive HIV-1 serum P24 antigen

               -  HIV-1 plasma viremia greater than 1000 copies/mL by polymerase chain reaction
                  (PCR) or branched-chain deoxyribonucleic acid (bDNA) method

               -  Detection of proviral DNA by PCR

        (If confirmation of HIV infection is not available then repeat testing of HIV antibody will
        be required)

          -  Two consecutive plasma HIV-1 RNA concentration less than 200 copies/mL. The two HIV-1
             RNA determinations ensure that the subject has been virologically-suppressed for at
             least 3 months prior to study entry:

               -  The subject must have a plasma HIV-1 RNA level less than 200 copies/mL using the
                  AmpliPrep/Taqman HIV-1 Test or Roche Amplicor HIV-1 Monitor Test Version 1.5
                  Ultrasensitive method at least 3 months prior to the screening visit, as the
                  "qualifying HIV-1 RNA."

               -  HIV-1 RNA less than 200 copies/mL measured by bDNA (Chiron 3.0) may be used as a
                  qualifying HIV-1 RNA for entry to the study but not for the confirmatory HIV-1
                  RNA.

               -  The subject must have a confirmed second plasma HIV-1 RNA less than 200 copies/mL
                  at screening, as the "confirmatory HIV-1 RNA."

               -  The subject must not have a plasma HIV-1 RNA greater than or equal to 200
                  copies/mL between the qualifying and confirmatory HIV-1 RNA measurements.

          -  Subjects receiving lipid-lowering agents (LLA) will be allowed; however, LLAs must be
             stable for greater than or equal to 3 months prior to study entry.

          -  Adequate renal function defined as a calculated CLcr greater than or equal to 50
             mL/min according to the Cockcroft-Gault formula

          -  Negative serum pregnancy test (females of childbearing potential only)

          -  Hepatic transaminases alanine aminotransferase (ALT) and aspartate aminotransferase
             (AST) less than or equal to 5 X upper limit of normal

          -  Males and females (of childbearing potential, ie, a non-menopausal female or a female
             with menopause < 2 years, and who has not had a hysterectomy, bilateral oophorectomy,
             or medically documented ovarian failure; this definition includes a young woman who
             has not yet started menstruating), and must agree to avoid pregnancy by sexual
             abstinence, or utilization of a highly effective method of birth control throughout
             the study period and for 30 days following discontinuation of study drug

          -  The ability to understand and sign a written informed consent form, which must be
             obtained prior to initiation of any study procedures

        Exclusion Criteria:

          -  Subjects receiving ABC/3TC and a PI without ritonavir

          -  Subjects receiving other ARV agents (eg, 2 protease inhibitors boosted with low-dose
             ritonavir (ie, "double-boosted PI regimens"), nonnucleoside reverse transcriptase
             inhibitors [NNRTIs], integrase inhibitors, TDF, or other nucleoside reverse
             transcriptase inhibitor [NRTIs]) in addition to ABC/3TC and a ritonavir-boosted
             protease inhibitor

          -  Have known resistance to any of the study agents at any time in the past including
             NRTI resistance mutations (including but not limited to K65R, L74V/I, M184V/I, or
             thymidine analog mutations) and/or PI resistance mutations

          -  A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed (with the
             exception of CD4 criteria) within 30 days of baseline

          -  Previous therapy with agents with systemic myelosuppressive, pancreatoxic, hepatotoxic
             or cytotoxic potential within 3 months of study start or the expected need for such
             therapy at the time of enrollment

          -  Proven or suspected acute hepatitis in the 30 days prior to study entry

          -  Anticipated need to initiate drugs during the study that are contraindicated with
             protease inhibitors (except upon approval by Gilead)

          -  Receiving ongoing therapy with any of the following (administration of any of the
             following medications must be discontinued at least 30 days prior to the Baseline
             visit and for the duration of the study period):

               -  Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir,
                  cisplatin, foscarnet, intravenous pentamidine, other agents with significant
                  nephrotoxic potential)

               -  Adefovir dipivoxil

               -  Probenecid

               -  Systemic chemotherapeutic agents (ie, cancer treatment medications)

               -  Systemic corticosteroids

               -  Interleukin-2 (IL-2)

               -  Investigational agents (except upon approval by Gilead)

          -  Pregnant or lactating subjects

          -  Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting
             which may confer an inability to receive an orally administered medication

          -  Current alcohol or substance abuse judged by the investigator to potentially interfere
             with subject adherence

          -  Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma.
             Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received
             any systemic therapy for KS within 30 days of baseline and are not anticipated to
             require systemic therapy during the study.

          -  Active, serious infections (other than HIV-1 infection) requiring parenteral
             antimicrobial therapy within 15 days prior to screening

          -  Prior history of significant renal or bone disease

          -  Any other clinical condition or prior therapy that, in the opinion of the
             investigator, would make the subject unsuitable for the study or unable to comply with
             the dosing requirements

          -  Known hypersensitivity to the study drugs, the metabolites or formulation excipients