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

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

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).

Study Overview

• Status: Completed
• Conditions: Aids, Cdc Group I
• Intervention / Treatment: Biological: AFO-18; Drug: Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau, Guinea-Bissau
    • Hospital Nacional Simao Mendes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HIV-1 seropositive with measurable viral load >10e3 copies/ml and CD4+ T-cell count >400 CD4+ cells/µl.
2. Not in Antiretroviral Therapy (>1 year).
3. Male or female with age between 18 and 50 years.
4. 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
5. Expected to follow the instructions.
6. Written informed consent after oral and written information.

Exclusion Criteria:

1. Vaccinated with other vaccines within 3 months before the first vaccination.
2. Treated with immune modulating medicine within 3 month before the first immunization.
3. Other important active chronic infectious diseases likely to influence the HIV-1 infection, like HIV-2, HBV, HCV and TB
4. Significant medical disease as judged by the investigators, for example severe asthma/COLD, badly regulated heart disease, insulin-dependent diabetes mellitus.
5. Severe allergy or earlier anaphylactic reactions.
6. Active autoimmune diseases.
7. Simultaneous treatment with other experimental drugs.
8. Laboratory parameters outside the 'normal' range for the area and which are considered clinically significant.
9. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Statens Serum Institut
• Collaborators: European and Developing Countries Clinical Trials Partnership (EDCTP); Ministry of the Interior and Health, Denmark
• Investigators: Study Director: Anders Fomsgaard, DMSc, Statens Serum Institut; Principal Investigator: Zacarias Jose da Silva, PhD, Bandim Health Project, Bissau, Guinea-Bissau

Publications and helpful links

General Publications

• Roman VR, Jensen KJ, Jensen SS, Leo-Hansen C, Jespersen S, da Silva Te D, Rodrigues CM, Janitzek CM, Vinner L, Katzenstein TL, Andersen P, Kromann I, Andreasen LV, Karlsson I, Fomsgaard A. Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau. AIDS Res Hum Retroviruses. 2013 Nov;29(11):1504-12. doi: 10.1089/AID.2013.0076. Epub 2013 Jun 21.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 9, 2010
• First Posted (Estimate): June 10, 2010

Study Record Updates

• Last Update Posted (Estimate): August 8, 2013
• Last Update Submitted That Met QC Criteria: August 2, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Therapeutic vaccine; AIDS vaccines; HIV-1 vaccine; Cellular immunity
• Other Study ID Numbers: HIV-BIS NCP03/2009; EDCTP_MSI.2009.10800.001 (Other Grant/Funding Number: EDCTP_MSI.2009.10800.001)