A phase IIa randomized, placebo controlled, double blinded study to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 14

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/*l (up to 2 occasional determinations * 350 cells/*l are allowed);
6. Current CD4+ cell count * 450 cells/*l;
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).
a. 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.
b. 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. History of 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
13. Any other condition, which, in the opinion of the investigator, may interfere with the evaluation of the study objectives

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>* To evaluate the safety and tolerability of intranodal iHIVARNA-01 vaccination<br /><br>compared with placebo, focusing on the nature, frequency and severity of local<br /><br>adverse events (pain, cutaneous reactions including induration) and systemic<br /><br>adverse events (temperature, chills, headache, nausea, vomiting, malaise, and<br /><br>myalgia).<br /><br>* To evaluate the immunogenicity of an immunization schedule with<br /><br>HIV-TriMix-mRNA (iHIVARNA-01) to increase the frequency of HIV-specific T-cell<br /><br>responses between baseline and 2 and 14 weeks after the last injection as<br /><br>compared to the control groups, immunized with TriMix-mRNA only or WFI only.</p><br>

Secondary Outcome Measures