Fig. 1

Experimental designs for in vivo efficacy testing of bNAbs, delivered passively or vectored, against HIV-1. Three designs are shown in increasing order of difficulty in achieving success. Schematics of viral load (red line) and bNAb concentration (blue line) over time are shown, and passive or vectored delivery of bNAb (blue arrows) and HIV-1 challenges (red arrows) are indicated. In these graphs, the bNAb neutralizes the HIV-1 strain, and escape mutations are not pre-existing nor emerge. HIV-1 can replicate when the bNAb is below a certain concentration. a, b Protection from HIV-1 challenge. c, d Maintenance of ART-suppressed virus in an analytical treatment interruption (ATI). ART treatment is interrupted after the desired bNAb concentration is achieved. The particular ART used may hinder second strand synthesis of rAAV, in which case the bNAb can be passively infused simultaneously with vectored delivery to maintain suppression (not shown). Viral reactivation from latent reservoirs continuously occurs, and greater viral dissemination prior to ART suppression likely increases the latency burden and frequency of reactivation events. e, f Suppression of replicating viremia. Millions to billions of viral particles are replicating and mutating when bNAb pressure is exerted, creating a selection force that advantages escape mutants. To achieve complete suppression, the bNAb will need to neutralize not just the dominant strain, but all of the existing minor strains and the potential emergent mutants in the viral quasispeices