A5388: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined with ART Initiation during Acute HIV Infection to Induce HIV Remission

Scientists are looking for ways to minimize the distribution of HIV-1 in the body, especially where anti-HIV medications (ART) are unable to reach. Starting ART as soon as possible following a diagnosis of Acute HIV Infection (AHI) has been shown to better preserve the immune system. Broadly neutralizing antibodies (bNAbs), when administered with ART, also have the potential to prevent the HIV virus from being able to reproduce.

This is a randomized, placebo-controlled research study that will enroll adults with recently diagnosed AHI. All participants will begin ART at entry and receive a single dose of two bNAbs (VRC07-523LS and PGT121.414.LS) or placebos. Everyone will be followed for about 1 year after starting ART, then stop ART for up to 2.5 years, then be followed for 1 year after restarting ART.

• To find out if bNAbs, VRC07-523LS and PGT121.414.LS, are safe for administration with ART.
• To evaluate if the bNAbs are effective at keeping HIV from reproducing. It is necessary to stop taking ART after receiving the bNAbs or placebos for bNAbs. This is referred to as an ATI (analytical treatment interruption).

• Documentation of recently confirmed HIV-1 (acute infection).
• Be between 18 and 70 years old.
• Be willing to take broadly neutralizing antibodies and start treatment for HIV.
• Not have taken pre-exposure ART (PrEP) within the past 60 days.
• No active hepatitis B or C infection or significant heart condition.

Participants will be randomized in a 2:1 ratio to either:

• Arm 1, and begin ART on the day of entry and receive one infusion each of VRC07-523LS and 414.LS.

OR

• Arm 2, and begin ART on the day of enrollment and receive two infusions of placebo for VRC07-523LS and PGT121.414.LS.

Participants will stop all ART between 1 year and 2 years after enrollment for up to 2.5 years. They will be closely monitored during the period that they are not taking ART. Participants will restart ART if their HIV viral load (the amount of HIV in the body) increases to a very high level, or there are other indicators that their HIV condition is getting worse. Participants will be followed for 1 year after restarting ART.

The broadly neutralizing antibodies (VRC07-523LS and PGT121.414.LS) or placebos and ART (bictagravir/emtricitabine/TAF) will be provided by the study.

Between 2 and 5 years.