Principal Investigator: Ayotunde E. Omoz-Oarhe (MD, MPH)

Study Objectives

Primary Objective:

To evaluate the safety and tolerability of intravenous infusions of 3BNC117-LS-J and 10-1074- LS-J in virally suppressed adults with HIV in sub-Saharan Africa.

To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J versus placebo in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) for 24 weeks after ART discontinuation in adults with HIV who have maintained viral suppression prior to the analytical treatment interruption (ATI) in sub-Saharan Africa.

Secondary Objective:

• To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J versus placebo in maintaining plasma HIV-1 RNA levels <50 copies/mL for 24 weeks after ART discontinuation in people/participants living with HIV (PWH) who have maintained viral suppression prior to the ATI.
• To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) while serum concentration of each bNAb remains ≥10 mcg/mL after ART discontinuation in PWH who have maintained viral suppression prior to the ATI.
• To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) for 24 weeks after serum concentration of each bNAb declines to <10 mcg/mL after ART discontinuation in PWH who have maintained viral suppression prior to the ATI.
• To evaluate the pharmacokinetic (PK) parameters of the combination of 3BNC117‑LS-J and 10-1074-LS-J during ATI in PWH in sub-Saharan Africa.
• To estimate the minimum effective concentrations of bNAbs required to maintain viral suppression.
• To evaluate evidence of anti-drug antibodies (ADA) against 3BNC117-LS-J and/or 10-1074-LS-J in samples collected at selected time points throughout the study.
• To evaluate the effects of the combination of 3BNC117-LS-J and 10-1074-LS-J on CD4+ T-cell count after ART discontinuation in adults with HIV who have maintained viral suppression prior to the ATI.

Study Design:

A5416/HVTN 806/HPTN 108 is a Phase I, randomized, double-blind, placebo-controlled trial designed to evaluate the effects of the combination of long-acting bNAbs 3BNC117-LS-J and 10-1074-LS-J or placebo in ART suppressed PWH who discontinue ART during a monitored ATI.

The study will enroll 48 participants, and aims for at least 40% enrollment of cisgender women, with an ideal goal of reaching 50 to 60% cisgender women out of the total number of participants.

Study population:

Individuals living with HIV, age ≥18 to ≤70 years, on stable ART who have a CD4+ count of ˃450 cells/μL, plasma viral load [VL] <50 copies/mL for at least 96 weeks prior to Step 1 entry, no history of receipt of any therapeutic HIV vaccine or HIV monoclonal antibody therapy

Sample size:

48 participants will be enrolled into Step 1:

Arm A (3BNC117-LS-J + 10-1074-LS-J): 32 participants

Arm B (placebo): 16 participants

In Botswana, we anticipate to enroll about 12 participants.

Study duration: 2 years

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)