A Trial to Evaluate the Safety and Tolerability of DV700P-RNA and DV701B1.1-RNA Immunization in Combination With Antiretroviral Analytical Treatment Interruption (ATI) in People Living With HIV for Elicitation of V3-glycan Antibodies

A Nonrandomized Phase 1 Clinical Trial to Evaluate the Safety and Tolerability of DV700P-RNA and DV701B1.1-RNA Immunization in Combination With Antiretroviral Analytical Treatment Interruption (ATI) in People Living With HIV for Elicitation of V3-glycan Antibodies

This phase 1 study will evaluate the safety, tolerability, and immune responses of two experimental mRNA HIV vaccines in adults living with HIV who are in overall good health. The study will enroll about 42 participants at multiple study sites. Researchers will assess whether these vaccines can start or strengthen antibody responses against HIV. The study will also evaluate how a closely monitored planned pause in antiretroviral therapy affects these immune responses.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV
• Intervention / Treatment: Biological: DV700P-RNA 100 mcg; Biological: DV701B1.1-RNA 100 mcg

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1427CEA
    • Fundacion Huesped CRS (Site ID: 31957)
    • Contact: Daniela P. Converso; Phone Number: 2013 54-1121209999; Email: daniela.converso@huesped.org.ar
• Peru
  • Lima, Peru, 15063
    • Barranco CRS (Site ID: 11301)
    • Contact: Consuelo T. Ramirez; Phone Number: 210 51-1-2067800
  • Lima, Peru, 15001
    • Via Libre CRS (Site ID: 31909)
    • Contact: Judith A. Jajaycucho Palomino; Phone Number: 156 51-01-2039900; Email: jjajaycucho@vialibre.org.pe
  • Lima, Peru, 15088
    • San Miguel CRS (Site ID: 11302)
    • Contact: Helen B. Chapa Garcia; Phone Number: 653 51-1-2067800; Email: hchapa@impactaperu.org
  • Provincia Constitucional del Callao
    • Bellavista, Provincia Constitucional del Callao, Peru, 07006
      • Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) (Site ID: 31970)
      • Contact: Fanny G. Rosas Benancio; Phone Number: 1007 51-1-4800401; Email: frosas@citbm.pe
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • Alabama CRS (Site ID: 31788)
      • Contact: Heather Logan; Phone Number: 205-873-8686; Email: heatherlogan@uabmc.edu
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • The Ponce de Leon Center CRS (Site ID: 5802)
      • Contact: Ericka Patrick; Phone Number: 404-616-6313; Email: erpatri@emory.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center / BIDMC VCRS (Site ID: 32077)
      • Contact: Jose Licona; Phone Number: 617-525-9433; Email: jlicona@partners.org
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Vaccine and Prevention CRS (Site ID: 30331)
      • Contact: Jennifer Han; Email: jhan23@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able and willing to provide informed consent.
• Age 18 to 60 years.
• Documented HIV infection.
• Lowest (nadir) CD4+ count between 250 and 450 cells/mm³.
• On stable combination antiretroviral therapy (ART) for at least 48 weeks prior to screening.
• Plasma HIV RNA <50 copies/mL for at least 48 weeks prior to enrollment, allowing limited transient increases.
• CD4+ count >450 cells/mm³ and CD4+ percentage ≥15%.
• Willing and able to comply with study visits and procedures.
• Agrees not to participate in another investigational study during participation unless approved.
• In general good health, with no clinically significant findings on physical exam or laboratory testing.
• Hemoglobin ≥11.0 g/dL (women) or ≥13.0 g/dL (men).
• Absolute neutrophil count ≥750/mm³.
• Platelet count ≥100,000/mm³.
• ALT <2.5 × upper limit of normal.
• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m².
• Serum creatinine ≤1.1 × upper limit of normal.
• Serum calcium >8.5 mg/dL.
• Blood pressure within acceptable limits.
• Agrees to use condoms during the specified period when ART is interrupted until HIV RNA is undetectable.
• No evidence of active hepatitis C infection.
• No evidence of active hepatitis B infection.
• For individuals of pregnancy potential: negative pregnancy test prior to enrollment and agreement to use effective contraception during the required study period.
• Agreement not to seek pregnancy during the required study period.

Exclusion Criteria:

• Current use of ART that includes non-nucleoside reverse transcriptase inhibitors (NNRTIs).
• Use of long-acting ART within 3 months prior to enrollment.
• Known resistance to any component of the current ART regimen (excluding M184V/I mutation).
• Resistance to one or more drugs in two or more ART classes (excluding M184V/I mutation).
• Initiation of ART during acute HIV infection (within 1 year of HIV acquisition, if known).
• History of advanced HIV-related illness (CDC Category C), except recurrent pneumonia, within 10 years prior to screening, or history of CD4 count <200 cells/mm³ within the past 10 years.
• History of severe HIV-related conditions, including opportunistic infections, HIV-associated cancers, lymphoma, neurocognitive disease, or progressive multifocal leukoencephalopathy.
• Active or recent non-HIV-related cancer requiring systemic treatment within 36 months or expected need for treatment within 12 months (excluding minor skin cancers).
• Active hepatitis B or hepatitis C infection.
• Significant liver disease, including cirrhosis or advanced fatty liver disease.
• Untreated or incompletely treated active or latent tuberculosis.
• Pregnancy or breastfeeding.
• Body mass index (BMI) ≥40 kg/m², unless approved.
• Diabetes mellitus, except well-controlled type 2 diabetes as allowed.
• History of or current atherosclerotic cardiovascular disease, including heart attack, angina, stroke, or peripheral arterial disease.
• Previous receipt of an investigational HIV vaccine (prior placebo recipients allowed).
• Receipt of a non-HIV investigational vaccine within 1 year, unless approved or licensed.
• Conditions causing impaired immune function or use of immunosuppressive medications within the specified timeframe.
• Prior receipt of anti-HIV monoclonal antibody therapy.
• Receipt of certain vaccines within restricted timeframes prior to enrollment (including live or mRNA vaccines within 4 weeks).
• Receipt of other vaccines within 14 days prior to enrollment.
• History of myocarditis or pericarditis.
• Recent initiation of allergy immunotherapy within 1 year (unless stable or approved).
• Recent use of investigational agents within restricted timeframes prior to enrollment.
• History of severe allergic reaction to mRNA vaccines or polyethylene glycol-containing products.
• History of angioedema.
• Idiopathic urticaria within the past year.
• Chronic urticaria or urticaria within the past year.
• History of urticaria associated with vaccination.
• Bleeding disorders or use of systemic anticoagulants.
• Conditions associated with increased risk of clotting or bleeding.
• History of seizures within the past 3 years or use of anti-seizure medications within that period.
• Absence of spleen or impaired splenic function.
• Active duty or reserve military personnel (U.S.).
• Any clinically significant medical, psychiatric, or substance use condition that may affect safety or study participation.
• Uncontrolled or severe asthma.
• History of immune-mediated medical conditions, except limited stable or resolved conditions as allowed.
• Allergy to local anesthetics (e.g., lidocaine).
• Difficulty with venous access that would interfere with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Participants will receive: Week 0: DV700P-RNA; Week 8: DV700P-RNA; Week 16: DV701B1.1-RNA	Biological: DV700P-RNA 100 mcg; Intramuscular injection; Biological: DV701B1.1-RNA 100 mcg; Intramuscular injection
Experimental: Group 2; Participants will receive: Week 0: DV700P-RNA; Week 8: DV701B1.1-RNA	Biological: DV700P-RNA 100 mcg; Intramuscular injection; Biological: DV701B1.1-RNA 100 mcg; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local reactogenicity following study product administration	Incidence and severity of solicited local reactogenicity signs and symptoms (injection site pain, erythema, and swelling), graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events	14 days following each vaccination
Systemic reactogenicity following study product administration	Incidence and severity of solicited systemic reactogenicity signs and symptoms (fever, fatigue, myalgia, arthralgia, headache, chills, nausea), graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events	14 days following each vaccination
Number and description of serious adverse events (SAEs)		Through study completion, expected to be up to 88 weeks
Number and description of medically attended adverse events (MAAEs)		Through study completion, expected to be up to 88 weeks
Number and description of adverse events of special interest (AESIs)		Through study completion, expected to be up to 88 weeks
Number and description of adverse events leading to study product discontinuation or participant withdrawal		Through study completion, expected to be up to 88 weeks
Number and description of adverse events (AEs) following study product administration		30 days following each vaccination
Response rate of differential serum neutralizing antibody responses to precursor detection viruses	Proportion of participants with serum antibody responses demonstrating differential neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay	At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses	Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay	At Baseline (Week 0) and 2 weeks after last vaccination
Response rate of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart	Proportion of participants with serum antibody responses demonstrating differential neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay	6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart	Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay	6 weeks after last vaccination and 8 weeks after ART restart

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Env-specific and V3-glycan-specific B cells	Frequency of total Env-specific and V3-glycan-specific B cells, as assessed by flow cytometry	At Baseline (Week 0) and 2 weeks after last vaccination
Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences	Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences, as assessed by B-cell sorting and BCR sequencing	At Baseline (Week 0) and 2 weeks after last vaccination
Frequency of Env-specific and V3-glycan-specific B cells after last vaccination and after ART restart	Frequency of total Env-specific and V3-glycan-specific B cells, as assessed by flow cytometry	6 weeks after last vaccination and 8 weeks after ART restart
Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences after last vaccination and after ART restart	Frequency of mutation of V3-glycan-specific B-cell receptor (BCR) sequences, as assessed by B-cell sorting and BCR sequencing	6 weeks after last vaccination and 8 weeks after ART restart
Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers	Proportion of participants with serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)	At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers	Magnitude of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)	At Baseline (Week 0) and 2 weeks after last vaccination
Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers	Epitope specificity of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)	At Baseline (Week 0) and 2 weeks after last vaccination
Response rate of neutralization activity against heterologous tier 2 viruses	Proportion of participants with neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay	At Baseline (Week 0) and 2 weeks after last vaccination
Magnitude of neutralization activity against heterologous tier 2 viruses	Magnitude of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay	At Baseline (Week 0) and 2 weeks after last vaccination
Breadth of neutralization activity against heterologous tier 2 viruses	Breadth of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay	At Baseline (Week 0) and 2 weeks after last vaccination
Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart	Proportion of participants with serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)	6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart	Magnitude of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)	6 weeks after last vaccination and 8 weeks after ART restart
Epitope specificity of serum IgG binding antibodies to autologous HIV Env stabilized trimers after last vaccination and after ART restart	Epitope specificity of serum IgG binding antibody responses to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)	6 weeks after last vaccination and 8 weeks after ART restart
Response rate of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart	Proportion of participants with neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay	6 weeks after last vaccination and 8 weeks after ART restart
Magnitude of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart	Magnitude of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay	6 weeks after last vaccination and 8 weeks after ART restart
Breadth of neutralization activity against heterologous tier 2 viruses after last vaccination and after ART restart	Breadth of neutralizing responses against heterologous tier 2 viruses, as measured by TZM-bl pseudovirus assay	6 weeks after last vaccination and 8 weeks after ART restart
Change in HIV Env sequence characteristics during ATI	Comparison of HIV envelope (Env) sequence evolution during analytic treatment interruption (ATI) between participants who develop V3-glycan-specific antibodies and those who do not	During ATI
Change in HIV gag sequence characteristics during ATI	Comparison of HIV gag sequence evolution during analytic treatment interruption (ATI) between participants who develop V3-glycan-specific antibodies and those who do not	During ATI

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Duke University; Department of Health and Human Services (HHS)

Study record dates

Study Major Dates

• Study Start (Estimated): June 2, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HVTN 808; 39218 (Other Identifier: DAIDS Document ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No