Entecavir Intensification for Persistent HBV Viremia in HIV-HBV Infection
Condition: HIV Infections; Hepatitis B
MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis B; Viremia; Hepatitis
Intervention: Entecavir with continued standard of care antiretroviral therapy; continued standard of care with tenofovir in addition to emtricitabine or lamivudine
Intervention description: 1 mg by mouth daily; continued standard of care with tenofovir in addition to emtricitabine or lamivudine
Intervention MeSH terms: Tenofovir; Lamivudine; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Entecavir; Anti-Retroviral Agents
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; Hepatitis B; treatment experienced

Summary:

      This study will evaluate HIV-HBV infected individuals who have evidence of HBV replication in
      the blood after taking 48 weeks of more of the HBV active medication tenofovir in combination
      with emtricitabine or lamivudine. Eligible participants will be randomized to receive 24
      weeks of entecavir (ETV) 1 mg versus continued standard of care antiretroviral therapy. After
      24 weeks, individuals on entecavir or who remain HBV viremic on standard of care will receive
      ETV o for an additional 24 weeks. The hypothesis is that intensification with entecavir will
      reduce HBV DNA at 24 weeks more than continued antiretroviral therapy without entecavir.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability and willingness to provide written informed consent

          -  HIV infection, documented in patient medical record. Acceptable forms of documentation
             include positive HIV antibody or detectable HIV RNA.

          -  Chronic HBV infection, defined as HBsAg positivity. Both hepatitis B "e" antigen
             (HBeAg) positive and negative subjects will be eligible.

          -  Detectable HBV DNA ( > 160 copies/ml) after 48 weeks of therapy with TDF in
             conjunction with either 3TC or FTC

          -  Compensated liver disease, defined as a Child-Pugh-Turcot(CPT) Score <7 at the time of
             enrollment.

        Note: If Bilirubin in elevated, direct and indirect bilirubin levels will be evaluated. If
        only indirect bilirubin elevated, direct bilirubin will be used for CPT score. If BOTH
        direct and indirect bilirubin are elevated, total bilirubin will be used for the CPT score.

          -  Stable antiretroviral therapy with no changes in the prior 8 weeks due to
             antiretroviral failure. HIV therapy modification for reasons other than virologic
             failure and without change in the tenofovir(TDF), lamivudine(3TC) or
             emtricitabine(FTC) moiety of the antiretroviral therapy will be permitted. HIV therapy
             must include TDF in conjunction with 3TC or FTC, and at least one other anti-HIV
             agent.

          -  HIV RNA of <75 copies/ml within 8 weeks of study enrollment.

          -  Estimated creatinine clearance by Cockcroft-Gault of ≥ 50 ml/min

          -  Serum alpha-fetoprotein (AFP) of ≤50 ng/ml within 8 weeks of study entry, or if
             elevated > 50 ng/ml, an imaging study demonstrating no evidence of hepatic tumor
             within 8 weeks of enrollment.

          -  Female study volunteers must not participate in a conception process (e.g., active
             attempt to become pregnant). If participating in sexual activity that could lead to
             pregnancy, the female study volunteer must use the following forms of contraception
             while receiving study-specific medication(s) and for 30 days after stopping the
             medication. One of the following methods MUST be used appropriately:

               -  Condoms1 (male or female) with or without a spermicidal agent

               -  Diaphragm or cervical cap with spermicide

               -  intrauterine device(IUD)

               -  Hormonal-based method

                    1. Condoms are recommended because their appropriate use is the only
                       contraception method effective for preventing HIV transmission.

        Note: Subjects with concomitant Hepatitis C infection will be permitted to enroll.

        Exclusion Criteria:

          -  Allergy or sensitivity to study drug

          -  Pregnancy, breastfeeding or unwillingness/inability to adhere to contraceptive methods
             for the duration of the study

          -  Prisoners or subjects who are incarcerated.

          -  Evidence of malignancy that would make the subject, in the opinion of the
             investigator, unsuitable for the study. This includes any systemic antineoplastic or
             immunomodulatory treatment or radiation within 24 weeks prior to study entry or the
             expectation that such treatment will be needed at any time during the study.

          -  Receipt of systemic corticosteroids within 90 days prior to study entry (as this
             medication may increase HBV replication).

          -  Investigational anti-HIV agents will be allowed on a case-by-case basis with the
             approval of the protocol team.

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.

          -  Any active medical, psychiatric or social circumstance that in the opinion of the
             investigator puts the subject at potential risk from study participation or makes
             adherence to the study protocol unlikely.

          -  Receipt of the following drugs with anti-HBV activity within 90 days prior to study
             entry or anticipated receipt during the course of the study including: adefovir(ADV),
             telbivudine, alpha interferon, penciclovir (Denavir) (except if given for < 4 weeks),
             famciclovir (Famvir), diaminopurine dioxolane (DAPD), clevudine (L-FMAU), thymosin
             alpha 1, ganciclovir (treatment limited to < 7 days is acceptable) (Cytovene),
             L-deoxythymidine, and L-deoxythymidine compounds and other investigational agents with
             anti-HBV activity.

          -  Receipt of nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin,
             cidofovir [Vistide], foscarnet [Foscavir], cisplatin, intravenous pentamidine
             [Pentam], oral tacrolimus [Prograf], cyclosporine [Sandimmune]) or the competitor of
             renal excretion, probenecid (Benemid), within 8 weeks prior to study entry or expected
             use of these agents during the course of the study. (Topical tacrolimus is allowed.)