DV700P-RNA and DV701B1.1-RNA HIV vaccines with ART interruption in adults with HIV

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.