HIV InfectionsPhase 1HVRRICANENCT04301154
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
A Phase 1 study testing HIVIS DNA/MVA-CMDR, HIVIS DNA + Cervarix and MVA-CMDR and Cervarix in people with HIV Infections, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 1 site in South Africa.
Trial 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 Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- HIVIS DNA/MVA-CMDR, HIVIS DNA + Cervarix and MVA-CMDR and Cervarix
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSouth Africa
- Study dates
- 18 Feb 2022to 16 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV perinatally infected
- Know their HIV+ status
- Initiated ART prior to 6 months of age
- Male and female ≥ 9 years old
- In generally good health
- Plasma viral load < 200 copies/ml on ART at screening
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- CD4 count above 400 cells/mm3 at screening
- Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study
- Negative urine β-HCG (human chorionic gonadotropin) pregnancy test for any female of childbearing age (post-menarche)
- Availability for follow-up for planned duration of the study
- 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.
- 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.
- 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
Who cannot join
- Participants who experienced virological failure necessitating ART modifications
- Participants who had ART interruption that lasted >2 weeks
- Prior or current pancreatitis or history of alcohol abuse.
- Systemic cortisone treatment within the past 30 days
- Participants coinfected with chronic hepatitis B (Hepatitis B surface antigen, HBsAg+) or hepatitis C (Hepatitis C antibody, HCV Ab+) at screening
- Participants with signs of autoimmune diseases
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- Participants with history of myocarditis
- Participants on any immune modulating or investigational drug
- Pregnant or breastfeeding female
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Stellenbosch University
Tygerberg Hills, Cape Town, 7505
About this study
Official title: 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
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
Read the 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.
- Conditions
- HIV Infections
- Being tested
- HIVIS DNA/MVA-CMDR, HIVIS DNA + Cervarix and MVA-CMDR, Cervarix
- Keywords
- HIV reservoir, Perinatally HIV Infected Children, Vaccine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIVIS DNA/MVA-CMDRBiological
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.
HIVIS DNA + Cervarix and MVA-CMDRBiological
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.
CervarixBiological
Cervarix by IM needle injection at weeks 0, 4 and 24.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (n=10): HIVIS DNA / MVA-CMDR | Experimental | Arm 1 (n=10) will receive 1500 micrograms (0.5ml) 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.
Participants who have been randomized to receive HIVIS DNA and MVA-CMDR alone (ARM 1) will be administered Cervarix after week 72, the last study follow-up visit, if required. Receives: Biological: HIVIS DNA/MVA-CMDR |
| Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR | Experimental | Arm 2 (n=10) will receive 0.5 ml of 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. Receives: Biological: HIVIS DNA + Cervarix and MVA-CMDR |
| Arm 3 (n=5): Cervarix | Experimental | Arm 3 (n=5) will receive 0.5 ml of Cervarix by IM needle injection at weeks 0, 4 and 24. Receives: Biological: Cervarix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Solicited and unsolicited serious adverse events
Safety
Measured: through study completion, an average of 1 year
Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells)
Efficacy
Measured: Change from Baseline at week 24, 36, 48, 60, 72
HIV DNA (copies/106 CD4+ T cells)
Efficacy
Measured: Change from Baseline at week 28, 48
Secondary outcomes (9)
Solicited and unsolicited non-serious adverse events
Safety
Measured: through study completion, an average of 1 year
Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA
Efficacy
Measured: Week 24, 36, 48, 60, 72
IUPM from total CD4+ T cells in blood by QVOA
Efficacy
Measured: Week 24, 36, 48, 60, 72
Plasma HIV RNA by SCA
Efficacy
Measured: Week 24, 36, 48, 60, 72
HIV-specific CD8+ and CD4+ T cells
Immunogicity
Measured: Week 28, 48
ADCC
Immunogicity
Measured: Week 28, 48
Binding and neutralizing Ab
Immunogicity
Measured: Week 28, 48
Global gene expression on PBMCs by RNA seq
immune response
Measured: Week 28, 48
Gene expression on HIV-specific CD8+ and CD4+ T cells
immune response
Measured: Week 28, 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2020
- Study start18 Feb 2022
- Primary completion16 Oct 2023
- Study completion16 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Merlin Robb, MD, Study chair, Henry M. Jackson Foundation for the Advancement of Military Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04301154
- Sponsor's protocol ID
- RV534
- Acronym
- HVRRICANE
- Status last verified
- Aug 2025
- First submitted
- 2 Mar 2020
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04301154
- Acronym / sponsor ID
- HVRRICANE / RV534
- Conditions
- HIV Infections
- Keywords
- HIV reservoir, Perinatally HIV Infected Children, Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Henry M. Jackson Foundation for the Advancement of Military MedicineUniversity, hospital or other
- Collaborators
- 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
- Study start
- 18 Feb 2022 (actual)
- Primary completion
- 16 Oct 2023 (actual)
- Study completion
- 16 Oct 2023 (actual)
- First posted
- 10 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (n=10): HIVIS DNA / MVA-CMDR | Experimental | Biological: HIVIS DNA/MVA-CMDRArm 1 (n=10) will receive 1500 micrograms (0.5ml) 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. Participants who have been randomized to receive HIVIS DNA and MVA-CMDR alone (ARM 1) will be administered Cervarix after week 72, the last study follow-up visit, if required. |
| Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR | Experimental | Biological: HIVIS DNA + Cervarix and MVA-CMDRArm 2 (n=10) will receive 0.5 ml of 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. |
| Arm 3 (n=5): Cervarix | Experimental | Biological: CervarixArm 3 (n=5) will receive 0.5 ml of Cervarix by IM needle injection at weeks 0, 4 and 24. |
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- HIV perinatally infected
- Know their HIV+ status
- Initiated ART prior to 6 months of age
- Male and female ≥ 9 years old
- In generally good health
Key exclusion criteria (9 listed)
- Participants who experienced virological failure necessitating ART modifications
- Participants who had ART interruption that lasted >2 weeks
- Prior or current pancreatitis or history of alcohol abuse.
- Systemic cortisone treatment within the past 30 days
- Participants coinfected with chronic hepatitis B (Hepatitis B surface antigen, HBsAg+) or hepatitis C (Hepatitis C antibody, HCV Ab+) at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIVIS DNA/MVA-CMDRHIVIS 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. | Biological | Arm 1 (n=10): HIVIS DNA / MVA-CMDR |
| HIVIS DNA + Cervarix and MVA-CMDRCervarix 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. | Biological | Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR |
| CervarixCervarix by IM needle injection at weeks 0, 4 and 24. | Biological | Arm 3 (n=5): Cervarix |
Primary outcome
Solicited and unsolicited serious adverse events
Time frame: 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)
Time frame: Change from Baseline at week 24, 36, 48, 60, 72
Efficacy
HIV DNA (copies/106 CD4+ T cells)
Time frame: Change from Baseline at week 28, 48
Efficacy
9 secondary outcomes
Solicited and unsolicited non-serious adverse events
Time frame: through study completion, an average of 1 year
Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA
Time frame: Week 24, 36, 48, 60, 72
IUPM from total CD4+ T cells in blood by QVOA
Time frame: Week 24, 36, 48, 60, 72
Plasma HIV RNA by SCA
Time frame: Week 24, 36, 48, 60, 72
HIV-specific CD8+ and CD4+ T cells
Time frame: Week 28, 48
ADCC
Time frame: Week 28, 48
Binding and neutralizing Ab
Time frame: Week 28, 48
Global gene expression on PBMCs by RNA seq
Time frame: Week 28, 48
Gene expression on HIV-specific CD8+ and CD4+ T cells
Time frame: Week 28, 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Merlin Robb, MD study chair
Henry M. Jackson Foundation for the Advancement of Military Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HIVIS DNA/MVA-CMDR, HIVIS DNA + Cervarix and MVA-CMDR and Cervarix in people with HIV Infections, run by Henry M. Jackson Foundation for the Advancement of Military Medicine at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Solicited and unsolicited serious adverse events (time frame: through study completion, an average of 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.