Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

Prior treatment

• Current receipt of ART other than NRTI and integrase inhibitor.
• Resistance to one or more drugs in two or more ARV drug classes.
• History of prior immunoglobulin (IgG) therapy.
• History of use of any immunomodulatory medications within 6 months prior to randomization
• Participation in another clinical study of an investigational product currently or within past 12 weeks

Other illness

• History of AIDS-defining illness, with the exception of recurrent pneumonia.
• History of or current clinical cardiovascular disease
• Current clinically significant acute or chronic medical condition
• History of HIV-associated neurocognitive disease
• History of an HIV-associated malignancy
• ART initiated during acute HIV infection
• Receipt of any therapeutic HIV vaccine or monoclonal antibody therapy (anti-HIV or otherwise) at any time in the past.

Other

• Breastfeeding or pregnancy

• HIV-1 infection
• On ART for at least 96 weeks prior to randomization
• On ART regimen containing an integrase inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) or dolutegravir/lamivudine for at least 6 weeks prior to randomization.
• CD4 cell count \>450 cells/mm\^3 within 90 days prior to randomization
• CD4 cell count nadir ≥200 cells/mm\^3.
• Plasma HIV-1 RNA levels of \<50 copies/mL for at least 96 weeks prior to randomization
• Select laboratory results within 90 days of randomization
• IC90 to 10-1074 of ≤1.5 mcg/mL, 10-1074 maximum percent inhibition (MPI) ≥98%, and IC80 to VRC07-523LS of ≤1 mcg/mL on the Monogram PhenoSense assay.
• QTcF interval ≤440 msec within 90 days prior to randomization.
• For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 30 days prior to randomization
• Cisgender women and transgender men of reproductive potential must agree to use two methods of contraception, if participating in sexual activity that could lead to pregnancy.
• Cisgender men and transgender women participants engaging in sexual activity that could lead to pregnancy and who are of reproductive potential must agree to use a barrier method of contraception
• Willingness to abstain from sexual intercourse or use a barrier method of contraception consistently
• Willingness to participate in an ATI.
• Weight \>50 kg and \<115 kg.
• Completion of pre-entry leukapheresis