Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion in Healthy, HIV-uninfected Adult Participants

General

Weight greater than 115 kg

Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 130/HPTN 089 PSRT

Investigational research agents received within 30 days before first study product administration

Intent to participate in another study of an investigational research agent or any other study that requires non-Network HIV antibody testing during the planned duration of the HVTN 130/HPTN 089 study

Pregnant or breastfeeding

Vaccines and other Injections

HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.

Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.

Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, PGT121, PGDM1400, or 10-1074

Immune System

Immunosuppressive medications received within 30 days before first study product administration (Not exclusionary: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatological condition; or \[4\] a single course of oral/parenteral prednisone or equivalent at doses less than 20 mg/day and length of therapy less than 14 days.)

Serious adverse reactions to VRC07-523LS, PGT121, PGDM1400, or 10-1074 formulation components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; see the protocol for more information), including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain

Immunoglobulin received within 90 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 130/HPTN 089 PSRT (for mAb see criterion above)

Autoimmune disease (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited AE assessments)

Immunodeficiency

Clinically significant medical conditions

Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

* A process that would affect the immune response,

* A process that would require medication that affects the immune response,

* Any contraindication to repeated infusions, or blood draws, including inability to establish venous or sub-cutaneous access.

* A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,

* A condition or process (eg, chronic urticaria or recent injection or infusion with evidence of residual inflammation) for which signs or symptoms could be confused with reactions to the study product, or

Any medical, psychiatric, occupational, or skin condition (eg, tattoos) that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, Solicited AEs, or a volunteer's ability to give informed consent

Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

Current anti-tuberculosis (TB) therapy

Asthma other than mild, well-controlled asthma (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:

* Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

* Uses moderate/high-dose, inhaled corticosteroids, or

* In the past year has had either of the following:

* Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;

* Needed emergency care, urgent care, hospitalization, or intubation for asthma.

Diabetes mellitus type 1 or type 2 (Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes)

Hypertension:

* If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.

* If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment.

Bleeding disorder diagnosed by a clinician (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)

Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study.)

Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.

Asplenia: any condition resulting in the absence of a functional spleen

History of hereditary angioedema, acquired angioedema, or idiopathic angioedema

What this study is about