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
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
60 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Local reactogenicity following study product administration — 14 days following each vaccination 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
Systemic reactogenicity following study product administration — 14 days following each vaccination 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
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 — At Baseline (Week 0) and 2 weeks after last vaccination 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
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses — At Baseline (Week 0) and 2 weeks after last vaccination Magnitude of serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant viruses, as measured by TZM-bl pseudovirus assay
Response rate of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart — 6 weeks after last vaccination and 8 weeks 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
Magnitude of differential serum neutralizing antibody responses to precursor detection viruses after last vaccination and after ART restart — 6 weeks after last vaccination and 8 weeks 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
Trial sites (16)
Facility
City
Region
Status
Alabama CRS (Site ID: 31788)
Birmingham
Alabama
Recruiting
The Ponce de Leon Center CRS (Site ID: 5802)
Atlanta
Georgia
Recruiting
The Hope Clinic of the Emory Vaccine Center CRS (Site #: 31440)
Decatur
Georgia
Not Yet Recruiting
Beth Israel Deaconess Medical Center / BIDMC VCRS (Site ID: 32077)
Boston
Massachusetts
Recruiting
Columbia P&S CRS (Site#: 30329)
New York
New York
Not Yet Recruiting
University of Rochester Vaccines to Prevent HIV Infection CRS (Site#: 31467)
Rochester
New York
Not Yet Recruiting
Penn Prevention CRS (Site#: 30310)
Philadelphia
Pennsylvania
Not Yet Recruiting
Houston Advancing Research Team CRS (Site # 31473)
Houston
Texas
Not Yet Recruiting
Seattle Vaccine and Prevention CRS (Site ID: 30331)
Seattle
Washington
Recruiting
Fundacion Huesped CRS (Site ID: 31957)
Buenos Aires
Buenos Aires
Not Yet Recruiting
Via Libre CRS (Site ID: 31909)
Lima
Lima Province
Not Yet Recruiting
Barranco CRS (Site ID: 11301)
Lima
Lima Province
Not Yet Recruiting
San Miguel CRS (Site ID: 11302)
Lima
Lima Province
Not Yet Recruiting
Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) (Site ID: 31970)
Bellavista
Provincia Constitucional del Callao
Not Yet Recruiting
Seke South CRS/30294 University of Zimbabwe -Clinical Trials Research Centre (UZ-CTRC)
Harare
Zimbabwe
Not Yet Recruiting
Spilhaus CRS/30314 University of Zimbabwe -Clinical Trials Research Centre (UZ-CTRC)
Harare
Zimbabwe
Not Yet Recruiting
More National Institute of Allergy and Infectious Diseases (NIAID) trials in Israel
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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