Background: Gut-associated lymphoid tissue (GALT) is preferentially infected during primary HIV infection (PHI) & is a key site of HIV persistence. α4β7 integrin, a gut-homing receptor expressed on CD4 T-cells, facilitates CD4 T-cell trafficking to GALT. A monoclonal antibody against α4β7 integrin (Vedolizumab, VDZ) is used to treat inflammatory bowel disease (IBD). Data from ART-treated SIV-infected primates showed HIV viral control following VDZ administration. We present 2 cases of HIV+ individuals treated with ART in PHI, who received VDZ for IBD.
Methods: VDZ was administered as licensed for IBD - at 0,2,6 then every 8 weeks. Informed consent for blood sampling & gut biopsy was obtained. Routine clinical monitoring data was captured (CD4,CD8 & HIV VL). Paired blood and gut biopsy samples from the terminal ileum (TI) & rectum were collected at a single time-point from participant A. Comparisons with blood & GALT samples from the HEATHER cohort (15 ART-treated PHI individuals) were made for β7 expression & total HIV DNA measured by flow cytometry and qPCR, respectively.
Results: Clinical characteristics are shown in Table 1. No adverse events were reported, and both patients had clinical IBD response. For Participant A: β7 expression on blood CD4+ cells increased over the 3 study visits (12.7%, 13.7% & 22.1%, respectively); β7 expression on GALT CD4+ cells was lower for participant A compared to HEATHER participants & healthy controls. Blood total HIV DNA for participant A (at biopsy) was comparable to the mean HEATHER HIV DNA (3.4 vs 3.1 Log/10⁶ CD4). Despite only 8 months of ART since PHI, total HIV DNA in GALT for participant A (TI 3.7, rectum 3.5 Log/10⁶ CD4 was below the mean of HEATHER participants (TI 3.6, rectum 3.5 Log/10⁶ CD4) whose median (range) time on ART was longer at 34 (15-96) months.
Conclusions: We report the first 2 cases of HIV+ individuals receiving Vedolizumab for IBD. It was shown to be safe, well-tolerated & associated with good IBD response. These preliminary data support further exploration of α4β7 integrin antibodies as a strategy to limit GALT HIV reservoir. It remains to be shown if longer treatment period may further impact on reservoirs.

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