HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease

Study Overview
=================
Brief Summary
-----------------
Treatment: Immunization with peptide-mix and adjuvant. The vaccine should induce cellular immunity against HIV-1. Target group: Untreated healthy individuals with chronic HIV-1 infection. Purpose: The primary purpose is to evaluate tolerability and safety of the vaccine. The secondary purpose is to evaluate the clinical effect of the vaccination treatment as measured by induction of immunity, lowering of viral load, induction of escape mutations in the virus and improvement in the patient CD4 lymphocyte blood counts. The third purpose is to evaluate the feasibility of conducting a therapeutic HIV immunization study in a poorly-resourced African setting. Design: The experiment is designed as a blinded, placebo-controlled phase 1 clinical trial in HIV-1 infected individuals in West Africa. Numbers of individuals: Phase I: 20 fully evaluable HIV-1-infected patients should enter the study (15 vaccine treated and 5 placebo(saline) treated controls).

Detailed Description
-----------------
The HIV infection does not leave lifelong immunity, but leads to break down of the immune system, opportunistic infections and death. The immunity obtained by the infection itself can only partially contain the HIV infection. The purpose with a targeted therapeutic vaccination is therefore in addition to the existing immunity to induce a broader, more powerful and more rationally or better directed immunity than the one induced by the natural HIV-1 infection. This would potentially lower the viral load in the blood making it more difficult to spread the virus to others and prolong the time to AIDS disease and medical treatment. There is a need for new rational vaccination possibilities, able to prevent (HIV) disease, postpone the need for antiretroviral medical treatment, prolong the life, and limit spread of HIV-1 in the population. The present protocol seak to introduce such a new immune treatment principle for HIV-1 infected individuals. In this study, individuals with chronic HIV-1 infection will be vaccinated with selected synthetic HIV immune-peptides representing new discovered conserved target´s on the virus. The vaccine should induce new immunity against several epitope targets on their HIV, whereby the HIV infection may be controlled for a longer time by the immune system. The purpose of the study is primarily to evaluate the safety and tolerability of the vaccine and secondary to evaluate the immunological and antiviral response in the vaccinated individuals.

Official Title
-----------------
Phase I Study: HIV-1 Peptide Immunisation of Individuals in West Africa to Prevent Disease

Conditions
-----------------
Aids, Cdc Group I

Intervention / Treatment
-----------------
* Biological: AFO-18
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV-1 seropositive with measurable viral load >10e3 copies/ml and CD4+ T-cell count >400 CD4+ cells/µl. Not in Antiretroviral Therapy (>1 year). Male or female with age between 18 and 50 years. Normal values for the area of liver and kidney enzymes, blood cell count with differential counts (e.g. white blood cells, lymphocytes, platelets/thrombocytes) and Hemoglobin Expected to follow the instructions. Written informed consent after oral and written information. Exclusion Criteria: Vaccinated with other vaccines within 3 months before the first vaccination. Treated with immune modulating medicine within 3 month before the first immunization. Other important active chronic infectious diseases likely to influence the HIV-1 infection, like HIV-2, HBV, HCV and TB Significant medical disease as judged by the investigators, for example severe asthma/COLD, badly regulated heart disease, insulin-dependent diabetes mellitus. Severe allergy or earlier anaphylactic reactions. Active autoimmune diseases. Simultaneous treatment with other experimental drugs. Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant. Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AFO-18<br>18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01) | Biological: AFO-18<br>* 18 peptides representing CD8 and CD4 epitopes mainly on HIV-1 in an adjuvants (CAF01)<br>* Other names: HIV-1 peptides;|
| Placebo Comparator: Saline<br>Saline | Drug: Saline<br>* 1.2 ml saline intramuscularly<br>* Other names: NaCl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability and Safety of the Treatment. | We report here the numbers of participants with vaccine related adverse events degree 3 or 4. Our goal for safety and tolerability was: Fewer than or 3 patients of the 15 vaccine treated show treatment related (reaction 3) side-effects of degree 3 or 4. | up to 6 months after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction of New T-cell Immune Response by the Vaccine | induction of new T-cell immune response against one or more of the vaccine epitopes using Interferon gamma Enzyme Linked Immuno spot assay (IFNg-ELISPOT assay)measuring Spot forming Unis per 1 million periferal blood mononuclear cells (SFU/1 mio PBMCs) above treshold (> 50 sfu/mio PBMC). | up to 6 months after last immunisation | 
| Lowering of HIV-1 RNA Viral-load in HIV-1 Immune Responders More Than 1 Log | changes (lowering) in Plasma HIV-1 RNA viral-load (measured by Quantitative RT-PCR kit, ROCHE) of more than 1 log | up to 6 months post immunization | 
| Increase in Blood CD4 T-cell Counts | Analyzed: Participants (minus drop-outs and withdrawn) with measured blood CD4 T-cell counts (cells/microliter). Reported: Numbers of participants obtaining an increase in measured blood CD4 T-cell counts post vaccination of >100 CD4 Tcell per microliter | up to 6 months post vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AIDS vaccines, HIV-1 vaccine, Therapeutic vaccine, Cellular immunity