Broadly neutralizing anti-HIV monoclonal antibodies (bNAbs) have shown promising results for the prevention and treatment of HIV. We present the results of Step 3 of BEAT2 evaluating whether the combination of bNAbs 3BNC117 and 10-1074 plus peg-IFN-?2b can prevent or delay the return of viremia during 26 weeks of ART interruption (ATI).
BEAT2 (NCT03588715) is an open-label study of the safety, tolerability and innate immune mechanisms activation of combining peg-IFN-?2b with two broadly neutralizing antibodies (3BNC117 and 10-1074) in the setting of well controlled chronic HIV infection and an ATI. Participants had bNAb sensitive virus using the Monogram DNA assay (IC90 < 2.0 µg/mL (3BNC117) and <1.5 µg/mL (10-1074)). Participants received 30 weekly doses of peg-IFN-?2b (1.5µg/kg) starting at step 2 (4 weeks on ART) and continued at step 3 (26 weeks of ATI), and seven paired IV injections of the bNAbs (30 mg/kg of each) at weeks 0, 2, 4 ,8 ,12, 16, 20 of step 3. Step 3 ended one week after last dose of peg-IFN-?2b. ART restart criteria: 6 weekly measurements > 1,000 copies/ml. Viral rebound: confirmed HIV-1 RNA of ?200 c/ml.
We enrolled 14 participants: 12 males, 11 African American, median CD4 count was 869 c/mm3 (IQR 739-1079) and nadir CD4 >200 c/mm3. 79% were on INSTI and 14% on PI regimens at entry. The combination immunotherapy was safe and well tolerated. 3 participants experienced infusion reactions during the administration of 3BNC117 (chills), 2 of them withdrew consent due to infusion chills during the intervention with undetectable HIV-1 RNA (at w5 and w10 of step 3). Two participants had viral rebound 2/14 (14%) (w8 and w14) during immunotherapy with 10/14 completing 26 weeks of step 3. No grade > 3 related AEs were observed. Participants maintained suppression during the ATI when compared to non-NNRTI historical chronically infected controls from prior ACTG studies (n=61) (Logrank Mantel-Cox p<0.0001; HR (logrank) 16.7 95%CI 9.9-27-9) (Figure).
Passive administration of a combination of bNAbs plus peg-IFN-?2b in subjects with susceptible virus maintains viral suppression for 26 weeks in the absence of traditional ART in most participants. We are currently evaluating step 3 effects on the HIV reservoir, as well as pharmacokinetics, immunological and virological parameters. These data will inform the next strategies to utilize bNAbs and interferon, alone or in combination in cure related strategies.