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.

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.