HIV Infections
Conditions
Keywords
HIV reservoir, Perinatally HIV Infected Children, Vaccine
Brief summary
Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens with or without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth
Detailed description
HIVIS DNA and MVA-CMDR vaccines induce immune responses important for clearing infected cells: broad HIV-specific CD8+ cytotoxic T cells, potent antibodydependent cellular cytotoxicity (ADCC), and binding antibody (Ab) and neutralizing antibody (NAb). The study include early treated children because of their healthy immunity and small HIV reservoirs. Giving licensed vaccine, Cervarix®, against human papilloma virus (HPV) that contains toll-like receptor (TLR) 4 agonist with HIVIS DNA could increase DNA antigen loading on dendritic cells and promote adaptive immune responses to the HIV vaccine.
Interventions
BIOLOGICALHIVIS DNA/MVA-CMDR
HIVIS DNA IM by needle-free injection at weeks 0 and 4 followed by intramuscular (IM) needle injection of 1 X 108 IU/mL (1ml) MVA-CMDR at weeks 24 and 36 in the same arm as HIVIS DNA.
BIOLOGICALHIVIS DNA + Cervarix and MVA-CMDR
Cervarix IM by needle injection followed by 1500 micrograms (0.5ml) per injection of HIVIS DNA IM by a needle-free injection device in the skin above (proximal to) the Cervarix injection (within 1.5 cm). They will receive 1 X 108 IU/mL (1ml) MVA-CMDR IM by needle injection at weeks 24 and 36 in the same arm as HIVIS DNA. They will also receive 0.5 ml Cervarix at the time of the first MVACMDR injection in the opposite arm from the MVA injection at week 24.
BIOLOGICALCervarix
Cervarix by IM needle injection at weeks 0, 4 and 24.
Sponsors
Bambino Gesù Hospital and Research Institute
PENTA Foundation
Johns Hopkins University
University of Miami
Leidos Biomedical Research, Inc.
Case Western Reserve University
Karolinska Institutet
Walter Reed Army Institute of Research (WRAIR)
Armed Forces Research Institute of Medical Sciences, Thailand
University of Padova
Chulalongkorn University
Henry M. Jackson Foundation for the Advancement of Military Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. HIV perinatally infected 2. Know their HIV+ status 3. Initiated ART prior to 6 months of age 4. Male and female ≥ 9 years old 5. In generally good health 6. Plasma viral load \< 200 copies/ml on ART at screening 7. CD4 count above 400 cells/mm3 at screening 8. Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study 9. Negative urine β-HCG (human chorionic gonadotropin) pregnancy test for any female of childbearing age (post-menarche) 10. Availability for follow-up for planned duration of the study 11. Passing a test of understanding is required for participants ≥ 18 years old or the parent(s)/legal representative of participants \< 18 years old before consent. 12. Written informed consent from participants ≥ 18 years old or parent(s)/legal representative of participants \< 18 years old. Assent by participants aged 9-17 years old will also be required. 13. Laboratory criteria within 8 weeks prior to enrollment * Hb \>11.0 g/dl * White blood cell count \>3000 cells/mm3 * Platelets \>125,000/ mm3 * ALT \<1.5 x upper limit of normal * Creatinine \<1.5 x upper limit of normal
Exclusion criteria
1. Participants who experienced virological failure necessitating ART modifications 2. Participants who had ART interruption that lasted \>2 weeks 3. Prior or current pancreatitis or history of alcohol abuse. 4. Systemic cortisone treatment within the past 30 days 5. Participants coinfected with chronic hepatitis B (Hepatitis B surface antigen, HBsAg+) or hepatitis C (Hepatitis C antibody, HCV Ab+) at screening 6. Participants with signs of autoimmune diseases 7. Participants with history of myocarditis 8. Participants on any immune modulating or investigational drug 9. Pregnant or breastfeeding female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Solicited and unsolicited serious adverse events | through study completion, an average of 1 year | Safety |
| Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells) | Change from Baseline at week 24, 36, 48, 60, 72 | Efficacy |
| HIV DNA (copies/106 CD4+ T cells) | Change from Baseline at week 28, 48 | Efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma HIV RNA by SCA | Week 24, 36, 48, 60, 72 | Efficacy |
| HIV-specific CD8+ and CD4+ T cells | Week 28, 48 | Immunogicity |
| ADCC | Week 28, 48 | Immunogicity |
| Solicited and unsolicited non-serious adverse events | through study completion, an average of 1 year | Safety |
| Global gene expression on PBMCs by RNA seq | Week 28, 48 | immune response |
| Gene expression on HIV-specific CD8+ and CD4+ T cells | Week 28, 48 | immune response |
| Binding and neutralizing Ab | Week 28, 48 | Immunogicity |
| Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA | Week 24, 36, 48, 60, 72 | Efficacy |
| IUPM from total CD4+ T cells in blood by QVOA | Week 24, 36, 48, 60, 72 | Efficacy |
Countries
South Africa
Outcome results
None listed