Complete HIV remission off treatment has not been possible. The aim was to evaluate the safety and efficacy of Vedolizumab(anti-?4?7 mAb) combined with ART to achieve permanent virological remission in ART naïve subjects after ART interruption.
Ten patients were enrolled with CD4-T cells count of >350 cells/µl and viral load >10.000 HIV-RNA copies/ml. The time of infection was 75[40-82] days. Patients started ART together with Vedolizumab infusions(300mg) at week 0, 4, 8, 12, 16, 20 and 24 weeks. At week 24(W24) ART and Vedolizumab treatment were interrupted. Biopsies were obtained from ileum(IL) and caecum(CC) at baseline(BL) and W24. Subjects were monitored monthly by measuring CD4+T-cell counts, viremia, Vedolizumab levels, HIV reservoir and flow cytometry to measure ?4?7 levels and immune check point molecules. Criteria to restart ART were CD4 T-cells below 350 cell/µl or viral load >105 HIV-RNA copies/ml in two consecutive measurements.
Vedolizumab was well tolerated and no adverse events occurred. No decreases in CD4+T-cell count were observed. Four patients restarted ART due to an increase of viral load(>105 HIV-RNA copies/ml). The other six patients completed the follow up with of 1590, 6250, 10000, 36450 and 4300 HIV-RNA copies/ml and no ART(Fig 1A). No differences on either time to restart ART or time to first plasma viremia of >1000 HIV-RNA copies/ml when compared to historical controls of ART interruption(n=24) were observed. Nevertheless, Vedolizumab trial group showed a viral load set point lower than the control group (p=0.008 (week40)). At W24, ?4?7 was completely blocked by Vedolizumab on peripheral CD4+ T-Cells, unlike on gut(Fig 1B). We observed a decrease in HIV-DNA on PBMCs(p=0.027), IL(p=0.003) and CC(p0.008); and in cell-associated HIV RNA on PBMCs(p=0.003), IL (p=0,019) and CC (p=0,002) together with a decrease in the expression of CD4-HLA-DR(p=0.009;p=0.002), LAG3(p=0.027;p=0.002), TIM3(p=0.002;p=0.002), and PD1(p=0.059;p=0.004) was observed in both tissue locations over the follow up. Reservoir was associated with the expression of CD4-?4?7(Fig 1C), PD1, TIGIT and LAG3 on PBMCs, IL and CC at W24.The decrease in cell associated HIV-RNA on PBMCs was prominent in sorted CD4+CD45RO+ ?7+ cells(p=0,011).
Vedolizumab was safe and well tolerated. No dramatic virological remission after ART interruption was found in naïve subjects. Reservoir establishment in PBMCs, IL and CC was associated with ?4?7 and immune check point molecules expression