Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Monoclonal Antibody PGT121.414.LS Administered Alone and in Combination With VRC07-523LS Via Intravenous or Subcutaneous Infusions in Healthy, HIV-uninfected Adult Participants

General

Weight \>115 kg

Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 136/HPTN 092 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 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 136/HPTN 092 PSRT will determine eligibility on a case-by-case basis.

Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 136/HPTN 092 PSRT will determine eligibility on a case-by-case basis.

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

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 \<20 mg/day and length of therapy \<14 days.)

Serious adverse reactions to VRC07-523LS or PGT121.414.LS formulation components (acetate, sucrose, polysorbate 80, histidine, and sorbitol; see study protocol), 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 136/HPTN 092 PSRT (for mAb see criterion above)

Autoimmune disease (Not excluded from participation: Participant 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 subcutaneous 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 participant'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 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 excluded: 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 ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤100 mm Hg diastolic. For these volunteers, blood pressure must be ≤140 mm Hg systolic and ≤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 ≥150 mm Hg at enrollment or diastolic blood pressure ≥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 3 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 generalized urticaria, angioedema, or anaphylaxis.

What this study is about