HAVARTI is a dose-ranging trial of vedolizumab and analytical treatment interruption (ATI) in HIV/ART.
Eight healthy HIV+ adults on ART for 2-10 years had vedolizumab given 3 times in 6 weeks before, and 4 times in 14 weeks after ATI, at 300mg doses in 4 (Group 1) and 150mg in 4 (Group 2). Monthly follow-up for adverse events (AE), plasma viremia (pVL) and T cell count outcomes informed clinical judgement for ART retreatment.
Groups had similar mean age, nadir CD4, pre-ART pVL, ART duration & baseline CD4 count. No serious clinical or severe laboratory AE occurred. One case had non-sustained pVL suppression <40 copies/mL in 2 sequential measures. CD4 T-cell count response varied, but none had sustained CD4 <350 cells/µL. Percent a4b7+ CD4 T cells in rectal mucosa decreased in Groups 1 and 2 respectively from 46.90 ±23.30 and 30.63 ±9.86 before, to 2.77 ±1.73 and 3.05 ±2.47 after vedolizumab. Group 1 pVL rebounded in 3 of 4 at 2 weeks, and all 4 at 6 weeks into ATI. pVL doubling time (T2) from ATI week 2 to 6 was 7.67 ±4.41 days, to a peak pVL level below pre-ART in each by mean 1.21 ±0.56 log10 copies/mL, sustained on average to 22 weeks, before a consistently rising pVL trajectory after 26 weeks, 12 weeks after last vedolizumab dosage. Group 2 pVL rebounded in 1 of 4 at 2 weeks, and all 4 at 6 weeks into ATI. T2 was 2.58 ±0.79 days, to week 6 peak pVL above pre-ART in 3 of 4 by mean 0.26 ±1.37, falling below mean pre-ART pVL to 14 weeks, with consistent rising trajectory onset after 18 weeks, 4 weeks after last vedolizumab dosage.
Viremia rebound appears attenuated in group 1 compared with group 2, supported by individual consistency of much slower T2 (p=0.057), and much lower pVL peak compared to pre-ART (by 1.47 log10), sustained 2 months longer after last vedolizumab dose. This difference is corroborated by historical controls with similarly calculated T2 of 3.4 days (and from literature about 2-3 days) and pVL rebound to +0.72 log10 > pre-ART at 6 weeks, as in Group 2. Limitations include small numbers, and high variation. Strengths include coherence of a biologically large effect size on pVL rebound dynamics, on kinetics and on time to loss of activity by dosage group, suggesting dose- and exposure-related vedolizumab effects. Deeper biological study in these cases, and further data from greater numbers, doses and duration is needed to validate and confirm activity of vedolizumab in pursuit of pVL suppression after ART.