Background:
BEAT2 (NCT03588715) is an open-label 50-week study in ART-suppressed PLWH undergoing ART substitution with 26 weeks of immunotherapy (IMM-Tx) [pegylated interferon alfa-2b (peg-IFN-α2b) and broadly neutralizing antibodies (bNABs) 3BNC117 and 10-1074], followed by an IMM-Tx free ATI up to 24 weeks. Primary results at week 38 are presented.
Methods:
Participants had baseline HIV bNAb-sensitive virus on PBMC using the PhenoSense mAb Assay (Labcorp-Monogram Bio.) (IC90 < 2.0 µg/mL (3BNC117) and < 1.5 µg/mL (10-1074)). Participants received A) 29 weekly doses of peg-IFN-α2b (1.5µg/kg) (Step 2 = 4 wks on ART and Step 3 = 26 wks off ART), and B) seven IV infusions of the bNAbs combination (30 mg/kg of each) at weeks 0, 2, 4 ,8 ,12, 16, 20 of Step 3. Step 4 (ATI: IMM-Tx cessation) was initiated after Step 3; Step 5 (ART re-start) triggered by 6 consecutive weekly measurements HIV VL > 1,000 c/ml. We measured reservoir size (IPDA) during Step 3, and bNAbs PK during Step 3 and 4. The primary end-point was not meeting ART re-treatment criteria in more than 10% (one sided 5% alpha level) at week 38. bNAbs sensitivity was evaluated upon viremia (plasma) and after re-starting ART when the HIV VL was < 50 c/ml (PBMC).
Results:
We enrolled 14 participants (12 males, 8 African American) (median CD4 count = 818 c/mm3 (IQR 739-1079); nadir CD4 > 200 c/mm3. Two participants voluntarily discontinued the study due to bNAbs infusion-related chills. IMM-Tx regimen was safe and well tolerated and maintained ART-free HIV suppression ( < 20 c/mL) for 26 weeks in 80% (10/12) of participants. Primary endpoint: 4 of 14 participants (28.6%) did not meet ART re-treatment criteria at 12 weeks of IMM-Tx cessation, and 2 (14.3%) maintained < 50c/ml for > 50 weeks. This rate was greater than observed in non-intervention ATI historical controls (p < 0.05). Variants resistant to both bNAbs emerged in two participants (14.3 %) during IMM-Tx (Figure). BNAb escape was detected during viral rebound in step 4 in 6/10 (60%) after IMM-Tx stopped. Resistance to bNAbs was detected after ART re-suppression in 5/13 persons (38.4%). No change from baseline in IPDA was noted at end of IMM-Tx (26 wks of Step 3).
Conclusions:
BNAbs and peg-IFN-α2b maintained 80% viral suppression for 26 weeks in the absence of ART, and results in subsequent improved viral control without effects on HIV reservoir. Selection of bNAb escape was observed in 75% of participants during IMM-Tx cessation.
