Oral tenofovir/FTC increases clearance of bNAb VRC01: implications for future research

Simon Collins, HIV i-Base

A paper published on 28 November 2023 in the journal Nature Communications reports a drug interaction between the drugs commonly used as PrEP and VRC01, a broadly neutralising antibody (bNAb) which was used in a large HIV prevention study. [1]

The results are from a post-hoc analysis of the VRC01 AMP study and reported that people using PrEP had 14% lower levels of the bNAb.

This subsidy included 48 participants in the VRC01 AMP study, half of whom were also using TD/FTC oral PrEP, and compared drug levels in each group.

Viral clearance of VRC01 was significantly faster (0.08 L/day, p = 0.005) in people using PrEP. Overall drug exposure was also significantly lower (dose-normalized area-under-the-curve of VRC01 serum concentration over time was 0.29 day/mL lower, p < 0.001).

The authors proposed a potential mechanism linked to oral PrEP increasing serum levels of intestinal Fatty Acid Binding protein (I-FABP), a marker of epithelial intestinal permeability.

VRC01 clearance is positively associated (r = 0.33, p = 0.03) with levels of serum I-FABP) which also increases when starting PrEP (p = 0.04) and after months of self-reported use (p = 0.001).

comment

Although PrEP was not widely used in the Antibody Mediated Prevention (AMP) study, which only produced a minimal protection against HIV infection in a subset of participants, people who were also taking tenofovir disoproxil/emtricitabine would have had lower levels of the antibody.

While the PrEP would have protected these participants against HIV, it might have complicated the interpretation of the impact of the antibody.

As this is the first report of an interaction between HIV drugs and HIV bNAbs these results might have implications for other research using bNAbs.

Because of the delay associated with journal publications, most new and significant drug interactions are first presented at a medical conference, especially when the findings might have safety implications for other ongoing research.

The paper was submitted to the journal six months ago, so these results could easily have been a late-breaker at the IAS conference in July.

I should also apologise in advance if the study was presented at an earlier meeting and we just missed this.

Reference

1. Huang Y et al. Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01. Nat Commun 14, 7813 (2023). (28 November 2023).
   https://doi.org/10.1038/s41467-023-43399-5
2. VRC01 antibody only prevents minority of HIV infections: AMP study results. HTB (21 February 2023).
   https://i-base.info/htb/39977