A5357: A Study of Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) to Maintain Viral Suppression in Adults Living with HIV-1

This study is for people with HIV who have an undetectable viral load. The study will evaluate the safety and effectiveness of a combination of two medications. The first drug is called long-acting cabotegravir (CAB), which will be given orally during Part 1 of the study and then as an injection every 4 weeks during Part 2 of the study. The second drug is called VRC07-523LS, which is a monoclonal antibody. A monoclonal antibody targets human proteins rather than attacking the virus directly. This drug will be given intravenously (directly into a vein) over about 15 to 30 minutes every 8 weeks.

• The study will see if cabotegravir and VRC07-523LS work well when taken together to keep HIV levels low.
• This study will also evaluate the safety of the drug combination.

People with HIV:

• Between the ages of 18 and 65
• On stable three-drug anti-HIV medications for a minimum of 8 weeks, with no history of switch due to virologic failure
• With a CD4+ cell count greater than or equal to 350
• With all HIV viral loads <50 copies within 2 years (one blip <200 OK), and at least two viral loads <50 copies within 12 months
• With no current hepatitis B or C infection
• Who have no history of seizures or treatment for seizures within the past 2 years
• With susceptibility to VRC07-523LS based on assay done at screening

Participants will be randomized to either:

Step 1: All participants will discontinue their current anti-HIV medications except for “nukes” and start oral CAB.

Step 2: Participants may receive CAB long-acting drug by injection every 4 weeks plus VRC07-523LS infusion by IV every 8 weeks for 48 weeks.

Step 3: Participants will be switched back to a Standard of Care oral HIV regimen.

The study provides oral and long-acting injectable cabotegravir and VRC07-523LS infusions. Standard of care oral medications will need to be locally sourced.

Participants will be on study for about 101 weeks.