Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1

Step 1 Inclusion Criteria:

• Individual with HIV-1
• On a three-drug ART regimen for at least 8 weeks that includes a boosted protease inhibitor (PI), a nonnuceloside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (INSTI) plus two nuclesodie reverse transcriptase inhibitors (NRTI) with no history of switch due to virologic failure.
• CD4+ cell count greater than or equal to 350 cells/mm^3
• Virally suppressed (< 50 copies/mL) within 2 years prior to study entry
• Susceptibility to VRC07-523LS based on IC50 less than or equal to 0.25 ug/mL and a Maximum Percent Inhibition > 98% using the Monogram PhenoSense Assay
• Certain laboratory values obtained within 60 days prior to study entry and in an acceptable range
• For participants of child-bearing potential:
• A negative serum or urine pregnancy test within 48 hours prior to study entry
• If participating in sexual activity that could lead to pregnancy, must agree to use an effective form of contraception.
• Negative HBsAg result
• Negative hepatitis C virus antibody
• Ability and willingness to provide written informed consent

Step 1 Exclusion Criteria:

• Any previous receipt of humanized or human monoclonal antibody (licensed or investigational).
• Weight greater than 115 kg or less than 53 kg.
• AIDS-defining illness within 60 days prior to study entry.
• History of a severe allergic reaction within 2 years prior to study entry.
• Currently breastfeeding or pregnant.
• Active drug or alcohol use or dependence that would interfere with adherence to study requirements.
• Acute or serious illness that requires systemic treatment, quarantine, and/or hospitalization within 30 days prior to entry.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.
• Treatment for hepatitis C within 24 weeks prior to study entry.
• Vaccinations within 7 days prior to study entry.
• Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records).
• Personal or known family history of prolonged QT syndrome or a clinically significant finding on the screening electrocardiogram (ECG) based on an assessment of the screening ECG by that site investigator.
• Unstable liver disease or known biliary abnormalities
• Moderate or severe hepatic impairment (Class B or C) as determined by Child-Pugh classification.
• History of seizures or treatment for seizures within the past 2 years prior to study entry.
• Current acute illness that in the opinion of the investigator will prevent the participant from complying with study visits.

Step 2 Inclusion Criteria:

• HIV-1 RNA less than 50 copies/mL at week 4 (Step 1), or HIV-1 RNA of 50-199 copies/mL at week 4 followed by HIV-1 RNA less than 50 copies/mL at week 5 (Step 1).
• For participants of child-bearing potential:
• A negative serum or urine pregnancy test within 48 hours prior to step 2 entry
• If participating in sexual activity that could lead to pregnancy, continued agreement to use an effective form of contraception.

Step 2 Exclusion Criteria:

• Discontinuation or temporary hold of oral CAB or NRTIs for greater than 7 consecutive days for any reason during Step 1.
• Grade 3 or 4 adverse event thought to be related to oral CAB during Step 1 according to the site investigator.
• Vaccination (e.g., influenza) within 7 days prior to the Step 2 registration.
• Currently breastfeeding or pregnant.
• Any greater than or equal to Grade 2 ALT (greater than 2.5 times ULN) that developed during Step 1.

Step 3 Inclusion Criterion:

• Received any CAB LA or VRC07-523LS during Step 2.

Step 3 Exclusion Criterion:

• None