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HIV-1-infectionPhase 1/2NCT06071767

Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1

A Phase 1/2 study testing ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 and MVA.tHIVconsv3 in people with HIV-1-infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 11 sites in 2 countries.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1-infection
What is being tested?
ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 and MVA.tHIVconsv3
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
36 participants
Where
11 sitesin 2 countries
Study dates
1 Apr 2024to 1 Aug 2029
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of written informed consent.
  • History of Initiation of combination ART within 90 days of acute HIV diagnosis
  • On ART for at least 12 months with no known ART interruption >28 consecutive days within 12 months prior to Step 1 Study Entry
  • ART with an integrase inhibitor-based regimen with two NRTIs or dolutegravir/lamivudine regimen for at least 6 weeks prior to Study Entry.
  • Willingness to participate in the ATI and willingness to restart ART according to study guidelines.
  • Willingness to adhere to protocol therapy and complete all study visits.
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  • Weight ≥50 kg and ≤150 kg at Screening.
  • CD4 cell count ≥450 cells/mm3 obtained within 60 days prior to Study Entry.
  • HIV-1 RNA <50 copies/mL (or below the assay limit of quantification if local assay lower limit of quantification is >50 copies/mL) for at least 1 year and within 60 days prior to Study Entry.
  • Select laboratory results within 60 days of study entry
  • For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 48 hours prior to or at study Entry.
  • Participants who are able to become pregnant and who are engaging in sexual activity that could lead to pregnancy must agree to use two methods of contraception, one of which must be a highly effective methods for contraception. Barrier methods of contraception are required for the second method of contraception.
  • Availability of results of HLA typing (required for randomization).
  • Completion of pre-entry leukapheresis or LVBD.

Who cannot join

  • Currently pregnant or breastfeeding or planning to become pregnant during study participation.
  • Prior receipt of anti-HIV broadly neutralizing antibody therapy.
  • Receipt of any non-HIV monoclonal antibody therapy within 1 year prior to study entry.
  • Prior receipt of a latency-reversing agent (LRA).
  • Receipt of HIV-1 or other investigational vaccines within 6 months prior to Study Entry.
  • Receipt of a live-virus vaccine within 60 days or any vaccination within 14 days prior to Study Entry.
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  • Receipt of any simian adenovirus-vectored vaccine (e.g., anti-COVID-19 AZD1222) within 12 months prior to Step 1 Study Entry.
  • Known allergy/sensitivity or any hypersensitivity to components of study treatments or their formulations.
  • Known severe chicken egg allergy.
  • Known history of a severe reaction or anaphylaxis to prior vaccinations or antibody preparations (e.g., intravenous immunoglobulin).
  • Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity).
  • Any history of anaphylaxis and related symptoms such as hives, respiratory difficulty, or angioedema.
  • Previous or current history of bleeding factor deficiency, coagulopathy or platelet disorder or on chronic anticoagulation.
  • History of inflammatory neurologic diseases.
  • History of pregnancy, head trauma or major surgery within 90 days prior to Step 1 Study Entry.
  • History of use of any immunomodulatory medications within the 6 months prior to Step 1 Study Entry.
  • Significant serious skin disease, such as but not limited to active rash, eczema, psoriasis, or urticaria.
  • Autoimmune disease (e.g., lupus, multiple sclerosis, and others) requiring ongoing immunosuppression.
  • Known history of CDC Stage 3 opportunistic infection (OI).
  • Any history of an HIV-associated malignancy.
  • Known or suspected active or untreated latent Mycobacterium tuberculosis infection.
  • Active or recent non-HIV-associated malignancy.
  • Serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry.
  • Known resistance to one or more drugs in two or more ARV drug classes.
  • History of or current clinical atherosclerotic cardiovascular disease
  • Current advanced liver disease.
  • Use of complementary or alternative medicines within 14 days prior study entry.

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States9 sites

  • Ponce de Leon Center CRS

    Atlanta, Georgia, 30308

  • Massachusetts General Hospital CRS (MGH CRS)

    Boston, Massachusetts, 02114

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27599

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Ohio State University CRS

    Columbus, Ohio, 43210

  • Houston AIDS Research Team CRS

    Houston, Texas, 77004

  • Penn Therapeutics CRS

    Philadelphia, Pennsylvania, 19104

  • University of California, San Diego AntiViral Research Center CRS

    San Diego, California, 92103

  • Washington University Therapeutics CRS

    St Louis, Missouri, 63110

Other trials in United States

Brazil2 sites

  • Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS

    Porto Alegre, Rio Grande do Sul, 91350-180

  • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

    Rio de Janeiro, Brazil

Other trials in Brazil

About this study

Official title: A Phase I/IIa Randomized, Placebo-Controlled Trial of Conserved-Mosaic T-cell Vaccine in a Regimen With Vesatolimod and Broadly Neutralizing Antibodies in Adults Initiated on Suppressive Antiretroviral Therapy During Acute HIV-1

The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) compared to placebo, to induce HIV-1 control during analytic treatment interruption (ATI).

Read the detailed description

A5374 is a phase I/IIa randomized, two-arm, double-blind placebo-controlled, multi-step strategy trial to evaluate safety and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) of the CD4 binding site and V3-loop base classes in individuals with HIV-1 who started suppressive antiretroviral therapy (ART) during acute HIV-1.

Participants will be screened for eligibility and have a pre-entry visit. After determination of eligibility, participants will be randomized prior to entry to either the active intervention arm (Arm A) or the placebo arm (Arm B) in a 2:1 ratio.

The study consists of four steps including an analytic treatment interruption (ATI) for all participants, and two subsequent optional steps including a second ATI for placebo participants.

  • Step 1: Study Intervention and ART (67 weeks)
  • Step 2: Analytic Treatment Interruption (up to 24 weeks)
  • Step 3: ART Restart (24 weeks)
  • Step 4: Continuation of ATI (up to 24 weeks)
  • Step 5 (optional): Study Intervention and ART (Placebo roll-over)
  • Step 6 (optional): Analytic Treatment Interruption 2 (ATI 2)

Each participant will complete Step 1 and Step 2. At any time on Step 2[mw1.1][KM1.2], participants on Arm A who meet criteria to restart ART will enter Step 3 and resume ART. Arm B (placebo) participants who have experienced virologic restart criteria may choose to enter Step 3 to resume ART or elect to enter Step 5 to resume ART and receive active study products. Participants who elect to enter Step 5 will undergo second ATI in Step 6. Participants who do not meet ART restart criteria after 24 weeks in Step 2 will enter Step 4 for an extended ATI.

Each participant will be enrolled for up to approximately 110 weeks. The total time on study for each participant is dependent on the time spent in the treatment interruption steps (Step 2 and 4).

Eligible participants participating in for Steps 5 and 6 will have up to 110 additional weeks on study.

Conditions
HIV-1-infection
Being tested
ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62, MVA.tHIVconsv3, MVA.tHIVconsv4, Vesatolimod (VES)
Keywords
Suppressive Antiretroviral Therapy, HIV, Acute HIV-1, HIV vaccine, T-cell vaccine, Therapeutic T-cell vaccine, ChAdOx1, MVA, Conserved region vaccine, HIVconsvX, Toll-like receptor 7 agonist, TLR7, Broadly neutralizing antibody, Antibodies, HIV antibody, HIV Broadly neutralizing antibody

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChAdOx1.tHIVconsv1Biological

    Administered as 0.4 mL intramuscularly (IM) at Week 0

  • ChAdOx1.HIVconsv62Biological

    Administered as 0.3 mL IM at Week 0

  • MVA.tHIVconsv3Biological

    Administered as 0.3 mL IM at Week 4

  • MVA.tHIVconsv4Biological

    Administered as 0.5 mL IM at week 4

  • Vesatolimod (VES)Drug

    VES 6 mg administered orally once every 2 weeks for two doses, then VES 8 mg once every 2 weeks for 8 doses. Dose escalation may be held or the 8 mg dose may be reduced for intolerability for weeks 6 through 24.

  • GS-5423Drug

    Also called 3BNC117-LS, Teropavimab

    Administered via intravenous (IV) infusion at week 7

  • GS-2872Drug

    Also called 10-1074-LS, Zinlirvimab

    Administered via IV infusion at week 7

  • MVA.tHIVconsv4Biological

    Administered 0.5 mL IM at week 60

  • PlaceboBiological

    Placebos for vaccines, VES, and bnAbs

Study groups in NCT06071767
Study groupRoleWhat they receive
Arm A: Active ChAdOx1 and MVA/HIVconsvX vaccines, vesatolimod and bnAbsExperimentalNot described
Receives: Biological: ChAdOx1.tHIVconsv1; Biological: ChAdOx1.HIVconsv62; Biological: MVA.tHIVconsv3; Biological: MVA.tHIVconsv4; Drug: Vesatolimod (VES); Drug: GS-5423; Drug: GS-2872
Arm B: Placebos for vaccines, vesatolimod and bnAbsPlacebo comparatorNot described
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of any serious adverse event (AE), Grade 3 or higher AE, or AE that leads to permanent discontinuation of study treatment regardless of grade, that is related to ChAdOx1-MVA/HIVconsvX vaccines, vesatolimod, GS-5423 or GS-2872

    Measured: Week 0 to Week 64

  2. Proportion of participants with viral control during an ATI defined as remaining off ART with HIV-1 RNA <1,000 copies/mL at Week 16 following ATI.

    Measured: Week 0 to Week 16 on Step 2

Secondary outcomes (13)

  1. Change in cell-associated HIV-1 RNA and DNA levels

    Measured: Weeks 0 to Week 24 on Step 2

  2. Change in plasma HIV-1 RNA viral load as measured by single copy assay (SCA)

    Measured: Weeks 0 to Week 24 on Step 2

  3. Change in intact proviral DNA levels (IPDA)

    Measured: Weeks 0 to Week 24 on Step 2

  4. HIV-1-specific T-cell responses to the conserved regions present in the vaccines as measured by IFN-γ ELISPOT - total frequency and breadth (number of recognized peptide pools out of 10).

    Measured: Week 0 to Week 24 on Step 2

  5. Change in soluble markers of systemic inflammation and immune activation: sCD163 (pg/mL)

    Measured: Weeks 0 to Week 24 on Step 2

  6. Change in soluble markers of systemic inflammation and immune activation: sCD14 (pg/mL)

    Measured: Weeks 0 to Week 24 on Step 2

  7. Change in soluble markers of systemic inflammation and immune activation: IL-6 (pg/mL)

    Measured: Weeks 0 to Week 24 on Step 2

  8. Change in soluble markers of systemic inflammation and immune activation: sTNFαR (pg/mL)

    Measured: Weeks 0 to Week 24 on Step 2

  9. Changes in soluble markers of systemic inflammation and immune activation: hsCRP (pg/mL)

    Measured: Weeks 0 to Week 24 on Step 2

  10. Time to first HIV-1 RNA ≥1000 copies/mL after ATI.

    Measured: Week 0 to Week 24 on Step 2

  11. Change in HIV-specific CD8+ T-cell-mediated viral inhibition as measured by in vitro virus inhibition assay (VIA) using representative viruses from major HIV-1 clades of group M.

    Measured: Weeks 0 to Week 24 on Step 2

  12. Occurrence of Medically Attended Adverse Events (MAAEs)

    Measured: Week 0 on Step 1 to 12 months following the last dose of study vaccination

  13. Occurrence of Adverse Events of Special Interest (AESIs)

    Measured: Week 0 on Step 1 to 12 months following the last dose of study vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2023
  2. Study start1 Apr 2024
  3. Primary completion29 Apr 2028 (estimated)
  4. Study completion1 Aug 2029 (estimated)

Why it stopped: Temporarily Closed (Paused) to Accrual and Study Agents/Products

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06071767
Sponsor's protocol ID
A5374
Other IDs
12025, HIV-CORE 009
Status last verified
Aug 2026
First submitted
5 Sep 2023
Last updated
2 Sep 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 and MVA.tHIVconsv3 in people with HIV-1-infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 11 sites in 2 countries.

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 14 inclusion and 27 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: paused, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Brazil. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Occurrence of any serious adverse event (AE), Grade 3 or higher AE, or AE that leads to permanent discontinuation of study treatment regardless of grade, that is related to ChAdOx1-MVA/HIVconsvX vaccines, vesatolimod, GS-5423 or GS-2872 (time frame: Week 0 to Week 64). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06071767.

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 2 Sep 2026.

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