Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01

Abstract

Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.gov #NCT02716675), we conduct a post-hoc analysis and find that VRC01 clearance is 0.08 L/day faster ( p = 0.005), and dose-normalized area-under-the-curve of VRC01 serum concentration over-time is 0.29 day/mL lower ( p < 0.001) in PrEP users ( n = 24) vs. non-PrEP users ( n = 24). Consequently, PrEP users are predicted to have 14% lower VRC01 neutralization-mediated prevention efficacy against circulating HIV-1 strains. VRC01 clearance is positively associated ( r = 0.33, p  = 0.03) with levels of serum intestinal Fatty Acid Binding protein (I-FABP), a marker of epithelial intestinal permeability, which is elevated upon starting PrEP ( p = 0.04) and after months of self-reported use ( p = 0.001). These findings have implications for the evaluation of future HIV-1 mAbs and postulate a potential mechanism for mAb clearance in the context of PrEP.

Abstract

Small molecule drugs can affect clearance of monoclonal antibodies, but this hasn’t been assessed for oral HIV-1 pre-exposure prophylaxis. Here, the authors find that faster serum clearance of an experimental IgG1 monoclonal antibody, VRC01, is associated with use of tenofovir-emtricitabine, possibly explained by increased epithelial intestinal permeability.