iHIVARNA Clinical Trial in HIV Infected Individuals
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: iHIVARNA-01; TriMix; Placebo
Intervention description: Therapeutic vaccination, followed by treatment interruption; Therapeutic vaccination, followed by treatment interruption; Therapeutic vaccination, followed by treatment interruption
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; mRNA; Lentivirus infection; Virus disease; Sexually transmitted disease; Immunodeficiency syndrome

Summary:

      iHIVARNA-01 is a novel therapeutic vaccine for the treatment of HIV-1-infected patients based
      on in vivo modification of DCs. It consists of HIVACAT-TriMix: mRNA encoding a mixture of APC
      activation molecules (CD40L, a constitutively active variant of TLR4 and CD70) and the HIV
      target antigens contained in HIVACAT to be administered through the intranodal route.
      iHIVARNA-01 aims to achieve the 'functional cure' of HIV infection, i.e. controlling viral
      replication in the absence of anti-retroviral therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. ≥ 18 years of age;

          2. Voluntarily signed informed consent;

          3. Proven HIV-1 infection (with documented antibodies against HIV-1 and a detectable
             plasma HIV-1 RNA before initiation of therapy);

          4. On stable treatment with cART regimen (antiretroviral therapy consisting of at least
             three registered antiretroviral agents) for at least 3 years;

          5. Nadir CD4+ ≥ 350 cells/μl (up to 2 occasional determinations ≤ 350 cells/μl are
             allowed);

          6. Current CD4+ cell count ≥ 450 cells/μl;

          7. HIV-RNA below 50 copies/mL in the last 6 months prior to randomization, during at
             least two measurements (occasional so called 'blips' ≤ 500 copies/mL are permitted);

          8. If sexually active, willing to use a reliable method of reducing the risk of
             transmission to their sexual partners during treatment interruption (including PrEP).

               1. For heterosexually active female, using an effective method of contraception with
                  partner (combined oral contraceptive pill; injectable or implanted contraceptive;
                  IUD/IUS; consistent record with condoms; physiological or anatomical sterility
                  (in self or partner) from 14 days prior to the first vaccination until 4 months
                  after the last vaccination.

        For heterosexually active male, using an effective method of contraception with their
        partner from the first day of vaccination until 4 months after the last vaccination. -

        Exclusion Criteria:

          1. Treatment with non-cART regimen prior to cART regimen;

          2. Previous failure to antiretroviral and/or mutations conferring genotypic resistance to
             antiretroviral therapy;

          3. Non-subtype B HIV infection;

          4. Active Hepatitis B virus and/or Hepatitis C virus co-infection;

          5. History of a CDC class C event (see appendix A);

          6. Pregnant female (screened with a positive pregnancy test), lactating or intending to
             become pregnant during the study;

          7. Active malignancy ≤ 30 days (extended period on the clinical assessment of the
             investigator) prior to screening;

          8. Active infection with fever (38°C or above) ≤ 10 days of screening and/or first
             vaccination;

          9. Therapy with immunomodulatory agents (e.g. systemic corticosteroids), including
             cytokines (e.g. IL-2), immunoglobulins and/or cytostatic chemotherapy ≤ 90 days prior
             to screening. This does not include seasonal influenza, hepatitis B and/or other
             travel related vaccines;

         10. Congenital, acquired or induced coagulation disorders, such as thrombocytopenia
             (thrombocytes < 150x109/L) and/or current use of anti-coagulant medication (e.g.
             coumarins, inhibitors of Xa); Usage of NSAIDs (including acetylsalicylic acid) is
             allowed, however it is advised to interrupt therapy 10 days ahead of vaccination;

         11. Usage of any investigational drug ≤ 90 days prior to study entry;

         12. An employee of the investigator or study site, with direct involvement in the proposed
             study or other studies under the direction of that investigator or study site, or is a
             family member of an employee or the investigator Any other condition, which, in the
             opinion of the investigator, may interfere with the evaluation of the study objectives