HIV Infections and Infestations Human immunodeficiency virus [HIV] disease
Conditions
Interventions
The clinical staff, volunteers and laboratory staff are all blinded during the study. The volunteers are randomly allocated to four arms (B1 - B4). Priming injections in arms B1 to B3 are conducted wi
Sponsors
Swedish Institute for Infectious Disease Control (SMI) (Sweden)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women 18 to 40 years of age 2. Negative antibody/antigen test for HIV infection 3. Willing to undergo HIV testing 4. Residents in Stockholm, at low risk of HIV and willing to remain so for the duration of the study 5. Low risk of HIV infection defined as: 5.1. No history of injecting drug use in the previous ten years 5.2. No gonorrhoea, chlamydia or syphilis during the last six months 5.3. No high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months 6. Willing to undergo a genital infection screening if need arises 7. Participants will agree to practice effective contraception from study entry until 4 months after the last immunization 8. Willing to practice safer sex for the duration of the study to avoid sexually transmitted infections 9. Good health as determined by medical history, physical examination and clinical judgment 10. No grade 1 or higher routine laboratory parameters 10.1. Hb >10.5g/dL 10.2. White blood cell count 1500/mm3 10.4. Lymphocytes >1.0 10.5. Platelets >120.000/mm3 10.6. CD4 >400/mm3 10.7. Glucose 2.5-7.0 mmol/L 10.8. Bilirubin <1.25xULN 10.9. Aspartate Aminostransferase (AST) <1.25xUNL 10.10. Alanine Aminotransferase (ALT) <1,25xUNL 10.11. Alkaline Phosphatase (ALP) <1.25xUNL 10.12. Creatinine <1.0xUNL 10.13. Complete urinalysis (UA). If microscopic UA confirms evidence of hematuria or proteinuria = 1+, the volunteer is ineligible) 11. Availability for the duration of the study 12. Able to give fully informed consent at screening visits 1 and 2
Exclusion criteria
Exclusion criteria: 1. Have active tuberculosis or other systemic infectious process, such as laboratory detection of tuberculosis bacteria, Hepatitis antigen, acute Hepatitis C, acute or active syphilis 2. Have a history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention, autoimmune disease, severe eczema 3. Have history of psychiatric, medical and/or substance abuse problems during the past 6 months that the investigator believes would adversely affect the volunteer's ability to participate in the trial 4. History of grand-mal epilepsy, or currently taking anti-epileptics 5. Have received blood products or immunoglobulin in the past 3 months 6. Are receiving ongoing therapy with immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy 7. Have used experimental therapeutic agents within 30 days of study entry 8. Have ECG deviations that indicate heart disease or would make interpretation of vaccine induced effect difficult 9. Have received any live, attenuated vaccine within 60 days of study entry (NOTE: Medically indicated subunit or killed vaccines [e.g., Hepatitis or influenza] are not exclusionary but should be given at least 2 weeks before or after HIV immunization to avoid potential confusion of adverse reactions) 10. Have previously received an HIV vaccine 11. History of severe local or general reaction to vaccination defined as 11.1. Local: extensive, indurated redness and swelling involving most of the antero-lateral thigh or the major circumference of the arm, not resolving within 72 hours 11.2. General: fever >= 39.5oC within 48 hours; anaphylaxis; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours. 12. Are study site employees who are involved in the protocol and may have access to the immunogenicity results 13. Unlikely to comply with protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety of immunization will be assessed by clinical signs and standard biochemical and haematological laboratory tests where any worsening of the severity grade will be considered for causality with the vaccine. The immunization will be evaluated by assessing local (pain, cutaneous reactions including indurations), general (fever, chills, headache, nausea, vomiting, malaise, myalgia) and other unsolicited adverse events within 28 days. Any grade III or IV event will be taken as an indication that the group of patients tolerate this schedule less well. The primary safety parameters will be graded: 1. Local adverse event Grade 3 or above (pain, cutaneous reactions including indurations) 2. Systemic adverse event Grade 3 or above (temperature, chills, headache, nausea, vomiting, malaise, or myalgia) 3. Other clinical or laboratory adverse events Grade 3 or above confirmed at examination or on repeat testing Any event attributable to vaccine leading to discontinuation of the immunisation regimen must be documented. Data on local and systemic events listed above will be solicited with specific questions or using a diary card for 7 days following each immunisation. Data on other clinical events and laboratory events will be collected with an open question at each visit and through routinely scheduled investigations. | — |
Secondary
| Measure | Time frame |
|---|---|
| A qualitative evaluation of cellular responses against peptides representing the different immunogens will be performed primarily by the ELISPOT technique. Additional testing will be performed by intracellular cytokine staining quantifying IFN-?, IL-2, TNF-a and MIP-1ß production by CD4 and CD8 T cells, lymphoproliferation against inactivated HIV using fresh cells and multi-colour intracellular cytokine staining using cryopreserved cells for assessment of multiple T cell effector functions including immunophenotyping of responding cells. Testing for binding antibodies and, if binding antibodies are present, also neutralizing antibodies will be performed. Group B1 will be compared with the ID only group (group A) in the HIVIS study (ISRCTN32604572) for evaluation of the lower dose of HIV DNA (0.6 vs 1.0 mg). Group B2 will be compared with Group B1 for evaluation of the lower dose of HIV DNA with and without electroporation. Group B3 will be compared to the group B2 for the evaluation of HIV DNA as a boost compared to boosting with HIV MVA. Group B4 will be compared to groups B1-B3 to show if priming with additional HIV-related plasmids will increase immunogenicity to any of the included antigens. | — |
Countries
Sweden
Outcome results
None listed