HIV-1 Infections and Infestations Unspecified human immunodeficiency virus [HIV] disease
Conditions
Interventions
The clinical staff and participants are blinded throughout the trial. The immunological laboratory is blinded during the study.
Priming injections: Injections of seven plasmids contai
Sponsors
Swedish Institute for Infectious Disease Control (SMI) (Sweden)
Muhimbili University of Health and Allied Sciences (MUHAS) (Tanzania)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Both males and females, age: 18 to 40 years 2. Willing to undergo counselling and HIV testing 3. Have a negative antigen/antibody ELISA for HIV infection 4. Able to give informed consent 5. Literacy corresponding to a minimum of 7 years of primary education 6. Resident in Dar es Salaam, and willing to remain so for the duration of the study 7. At low risk of HIV infection, defined as the absence of an identifiable risk factor/ behaviour: 7.1. Sexual partner with HIV 7.2. Sexual partner with unknown HIV serostatus who is also unwilling to use protective condoms consistently in all sexual relations 7.3. Sexual partner is known to be at high risk for HIV 7.4. More than one sexual partner in the last 6 months 7.5. History of being an alcoholic (as medically defined or more than 35 units /week) 7.6. History of STI within the past 6 months 8. Verbal assurances that adequate birth control measures are used not to conceive/father a child during the study and up to 4 months after the last vaccine injection 9. Have a negative urinary pregnancy test 10. Be willing to practice safe sex for the duration of the study to avoid sexually transmitted infections including HIV. 11. Good health as determined by medical history, physical examination, clinical judgment and by key laboratory parameters (reference ranges are in accordance with data generated at MUHAS for haematology values, and that generated at Mbeya (MMRP) for biochemical parameters. Exclusion by presence of Diabetes mellitus will be based on the WHO cut-off value of a fasting blood glucose 10.5g/dl 11.2. White blood cell count >1,300/mm^3 11.3. Granulocytes >6.4/mm^3 11.4. Lymphocytes >1.0/mm^3 11.5. Platelets >120,000/mm^3 11.6. CD4 >400 cells/mm^3 11.7. Random blood glucose 2.5-7.0 mmol/L; if elevated, then a fasting blood glucose =1+, obtain complete urinalysis (UA). If microscopic UA confirms evidence of haematuria or if proteinuria >=1+, the volunteer is ineligible)
Exclusion criteria
Exclusion criteria: 1. Active tuberculosis or other systemic infectious process elicited by review of systems, physical examination and laboratory detection, such as detection of Hepatitis B surface antigen, or active syphilis 2. Have a history of immunodeficiency, chronic illness requiring continuous or frequent medical intervention 3. Autoimmune disease by history and physical examination 4. Severe eczema 5. Have a 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. 6. History of grand-mal epilepsy, or currently taking anti-epileptics 7. Have received blood or blood products or immunoglobulins in the past 3 months 8. Are receiving immunosuppressive therapy such as systemic corticosteroids or cancer chemotherapy. 9. Have used experimental therapeutic agents within 30 days of study entry 10. Have received any live, attenuated vaccine within 60 days of study entry. (Note: Medically indicated subunit or killed vaccines {e.g., hepatitis A or hepatitis B] are not exclusionary but should be given at least 2 weeks before or after HIV immunisation to avoid potential confusion of adverse reactions) 11. Have previously received an HIV candidate vaccine 12. History of severe local or general reaction to vaccination defined as: 12.1. Local: Extensive, indurated redness and swelling involving most of the major circumference of the arm, not resolving within 72 hours 12.2. General: Fever >=39.5°C within 48 hours, anaphylaxis, bronchospasm, laryngeal oedema, collapse, convulsions or encephalopathy within 72 hours 13. Are lactating mothers 14. Are study site employees who are involved in the protocol and may have direct access to the immunogenicity results 15. Unlikely to comply with protocol as judged by the principal investigator or his designate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety: 1.1. Samples for routine biochemistry and haematology (see inclusion criteria) were obtained at screening, before and 2 weeks after each immunisation, and 3 month after the last DNA and MVA immunisation 1.2. 12-lead electrocardiograms were performed before and 2 weeks after the MVA injection 1.3. Clinical adverse reactions and vital signs at 10 and 30 minutes, in addition a contact was made by telephone 1-3 days after each injection 1.4. A 7-day diary card (including standardised measurements of body temperature) was filled in and presented at the visit 2 weeks after each injection, when direct questions were asked on the basis of the diary card 2. Specific reactivity to HIV-1 peptides in IFN-gamma enzyme-linked immunosorbent spot (ELISpot), performed on fresh peripheral blood mononuclear cell (PBMC) before the first DNA and the MVA immunisation and 2 weeks after the last DNA and MVA immunisation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The following will be performed on fresh PBMC before the first DNA and the MVA immunisation and 2 weeks after the last DNA and MVA immunisation: 1.1. Specific reactivity to HIV-1 peptides in IL-2 ELISpot 1.2. Lymphoproliferation to inactivated whole HIV-1 virions 2. A qualitative and quantitative presence of necessary infrastructure and human capacity to conduct HIV-related vaccine studies at MUHAS | — |
Countries
Tanzania
Outcome results
None listed