Safety and Efficacy of Neutralizing Antibodies and Vaccination for Induction of HIV Remission

Exclusion Criteria

• •Participants who meet any of the following criteria will be excluded from the study:
• •1. Weight \<50 kg or \> 115 kg
• •2. Presence of HLA allele associated with viral control including HLA B\*57:01 or HLA B\*58:01 (based on archived data from RV254)
• •3. Anyone with contraindication to intramuscular injections, placement of intravenous lines, and blood draws
• •4. Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to entry.
• •5. Any clinically significant acute or chronic medical condition, that in the opinion of the investigator would preclude participation including cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological disorders, that in the opinion of the investigator would preclude participation (e.g., history of seizure disorders, cardiovascular disease, bleeding/clotting disorder, autoimmune disease, malignancy, poorly controlled asthma, active tuberculosis or other systemic infections, etc.)
• •1. Participants with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) including untreated syphilis, gonorrhea or chlamydia infection or temperature ≥38.0ºC within 24 hours prior to the first dose of IP will not enter baseline. Participant will be referred for treatment, and participant is eligible for repeat screening and potential study entry once treatment is successfully completed
• •2. Major surgery (per the Investigator's judgment) within 12 weeks before screening or plan to have major surgery during the time of study participation
• •• surgical procedures to be conducted under local or loco-regional anesthesia and not judged as major by the Investigator may participate.
• •3. Current or history of an HIV-associated malignancy (including Kaposi's sarcoma), and any type of lymphoma, or virus-associated cancers
• •4. Current or history of non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the 36 months prior to screening
• •• Minor surgical removal of localized skin cancers (squamous cell carcinoma, basal cell carcinoma) or carcinoma in situ of the cervix is not exclusionary
• •5. Current or history of clinical atherosclerotic cardiovascular disease, as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following: acute myocardial infarction, acute coronary syndromes, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), peripheral arterial disease presumed to be of atherosclerotic origin
• •6. Current or history of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up)
• •7. Current or history of advanced liver disease (non-alcoholic fatty liver disease, steatohepatitis, or alcoholic liver disease) with known or suspected cirrhosis or fibrosis score ≥F2.
• •8. Current or history of TTS, or heparin-induced thrombocytopenia and thrombosis syndrome.
• •9. Current or history of acute polyneuropathy e.g. Guillain-Barré syndrome
• •10. Current or history of CDC Category C event
• •6. Active or chronic hepatitis B virus infection (detectable HBsAg, HBV DNA, or both)
• •7. Hepatitis C infection (HCV antibody positive)
• •8. Receipt of a licensed or Emergency Use Authorization vaccine within 4 weeks prior to study screening or plans to receive live attenuated vaccines within 4 weeks or any other licensed or Emergency Use Authorization vaccine within 2 weeks prior to or 2 weeks after any of the study investigational product administrations.
• •9. Receipt of an investigational study agent within 12 months prior to study screening
• •10. Previous receipt of immunoglobulin (IgG) therapy Note: Individuals who received IgGs as prophylactic therapy (i.e., for HBV or rabies exposure) \>12 months prior to screening will not be excluded.
• •11. Previous receipt of humanized or human monoclonal antibody whether licensed or investigational Note: Individuals who received monoclonal antibody for the prevention and/or treatment of SARS-CoV-2/COVID-19 \>12 months prior to screening will not be excluded.
• •12. Previous participation in a candidate HIV vaccine study or immune prophylaxis for HIV-1 infection with confirmed receipt of active product or with unknown receipt of active product vs placebo (i.e. remains blinded to what was actually received).
• •13. History of use of any immunomodulatory medications within 6 months of study entry including systemic corticosteroids (\>14 days), immunosuppressants, anti-cancer drugs, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect Note: Topical or inhaled corticosteroids are not prohibited.
• •14. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines, vaccine products, neomycin, streptomycin, gentamicin or egg products
• •15. History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment
• •16. History of chronic urticaria requiring daily treatment or a history of chronic or recurrent eczema and/or atopic dermatitis
• •17. History of splenectomy
• •18. EKG abnormality within 90 days prior to or at screening, including but not limited to second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (regardless of gender or sex), or clinically important arrhythmia that would interfere with the assessment of myocarditis/pericarditis or QTc interval.
• •19. QTc interval \>440 ms within 90 days prior to or at screening
• •20. Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling).
• •21. Pregnant, breastfeeding or planning to become pregnant while enrolled in this study
• •22. Major psychiatric illness and/or substance use during the past 12 months that in the opinion of the investigator would preclude participation
• •Enrolled participants who meet any of the following criteria will be excluded from moving to Step 2:
• •1. Virologic failure (two consecutive HIV-1 RNA \>1000 copies/mL) after study entry
• •2. Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during ATI.
• •3. Receipt of any non-nucleoside reverse transcriptase inhibitor (NNRTI) within 60 days before Step 2 entry.
• •4. Receipt of long-acting ART such as long-acting cabotegravir (CAB LA) or long-acting rilpivirine (RPV LA) at any point after Step 1 entry.
• •5. Failure by the participant to attend three consecutive Step 1 study visits.
• •6. Pregnancy or breastfeeding.
• •7. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.