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

Inclusion Criteria

General and Demographic Criteria

• Age of 18 to 50 years
• Access to a participating Clinical Research Site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
• Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria:

• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit (see study protocol).

Laboratory Inclusion Values:

Hemogram/Complete Blood Count

• Hemoglobin ≥11.0 g/dL for participants who were assigned female sex at birth, ≥13.0 g/dL for participants who were assigned male sex at birth. For transgender participants who have been on feminizing hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for persons assigned female sex at birth).
• White blood cell (WBC) count = 2,500 to 12,000 cells/mm^3
• WBC differential either within institutional normal range or with site clinician approval
• Platelets = 125,000 to 550,000 cells/mm^3

Chemistry

• Chemistry panel: alanine aminotransferase (ALT) 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 med