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

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.