A Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of PGDM1400LS Alone and in Combination With VRC07-523LS and PGT121.414.LS in Healthy, HIV-uninfected Adult Participants

Inclusion Criteria

• Age of 18 through 50 years
• Access to a participating 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
• 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 Appendix J and Appendix K).
• Hemoglobin
• ≥ 11.0 g/dL for volunteers who were assigned female sex at birth
• ≥ 13.0 g/dL for volunteers who were assigned male sex at birth and transgender males who have been on hormone therapy for more than 6 consecutive months
• ≥ 12.0 g/dL for transgender females who have been on hormone therapy for more than 6 consecutive months
• For transgender volunteers who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth
• White blood cell count = 2, 500 to 12,000 cells/mm3
• WBC differential either within institutional normal range or with site clinician approval
• Platelets = 125,000 to 550,000 cells/mm3
• 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 140/HPTN 101 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 140/HPTN 101 study
• Pregnant or breastfeeding
• HIV vaccine(s) received in a prior HIV vaccine trial. Volunteers who have received control/placebo in an HIV vaccine trial are not excluded.
• SARS-CoV-2 vaccine(s) received within 7 days prior to HVTN 140/HPTN 101 enrollment or planned within 7 days after enrollment.
• Receipt of humanized or human mAbs, whether licensed or investigational.
• Previous receipt of mAbs VRC01, VRC01LS, VRC07-523LS, PGDM1400, PGT121, PGT121.414.LS.
• 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 PGDM1400LS, VRC07-523LS, or PGT121.414.LS formulation components (see Section 8.2) including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• Immunoglobulin received within 60 days before first study product administration (for mAb see criterion 8 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 CRS investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited AE assessments.)
• Immunodeficiency
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or pas