PROLONGED VIRAL SUPPRESSION BY IMMUNOTHERAPY WITH ANTI-HIV ANTIBODIES 3BNC117/10-1074

Presented During:

Monday, Feb 14, 2022: 2:00 PM - 3:30 PM MST

Abstract Submission Number:

361 

Abstract Type:

General Abstract  

Authors:

Christian Gaebler1, Lilian Nogueira1, Elina Stoffel1, Thiago Oliveira1, Katrina Millard1, Martina Turroja1, Allison Butler1, Victor Ramos1, Michael Seaman2, Jacqueline D. Reeves3, Johannes F. Scheid4, Rajesh T. Gandhi4, Tae-Wook Chun5, Marina Caskey1, Michel Nussenzweig1

Institutions:

1The Rockefeller University, New York, NY, USA, 2Beth Israel Deaconess Medical Center, Boston, MA, USA, 3Abivax, Paris, France, 4Massachusetts General Hospital, Boston, MA, USA, 5National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

Presenting Author:

Dr Christian Gaebler  
The Rockefeller University

Background:

Broad and potent monoclonal anti-HIV-1 antibodies (bNabs) comprise a promising class of immunotherapeutics that have the potential to suppress HIV-1 infection, increase the rate of infected cell clearance and enhance anti-HIV immunity. However, bNabs have only been tested in short term studies and their effects on the intact latent reservoir have not been interrogated in depth. Here we report on a clinical study in which people living with HIV who started ART during chronic infection received 7 doses of a combination of two bNabs over a period of 20 weeks in the presence or absence of antiretroviral therapy (ART).

Methods:

We conducted a phase 1b, open label, randomized clinical trial of the combination of two bNabs, 3BNC117 and 10-1074, in the presence or absence of ART, including two study groups of people living with HIV-1 on suppressive ART for at least 12 months prior to entry (NCT03526848). Participants in Group 1 discontinued ART 2 days after the first 3BNC117 and 10-1074 infusions, while participants in Group 2 remained on ART during the period of antibody infusions through week 26 (Fig. 1a). ART was resumed according to pre-specified criteria. Participants in both groups received up to seven infusions of 30 mg/kg of each antibody over the course of 20 weeks, and were followed for a total of 48 weeks from enrollment.

Results:

Of the 26 (23 male, 3 female) enrolled participants, 18 and 8 were randomized to Group 1 or 2, respectively. Repeated antibody infusions over the course of 20 weeks were generally safe and well-tolerated. Without pre-screening for antibody sensitivity Group 1 participants maintained viral suppression for a median of 28.5 weeks in the absence of ART which was significantly longer than after 3 infusions over 6 weeks and historical controls from non-interventional ATI studies (Fig.1b, Log-rank Mantel-Cox P = 0.0224 and P < 0.0001, respectively). Rebound viremia generally occurred after one of the two antibodies reached a concentration below 10 micrograms per milliliter and 2 of 17 participants in Group 1 that underwent ATI maintained viral suppression for at least 48 weeks (Fig. 1b).

Conclusions:

We conclude that combination anti-HIV-1 antibody therapy can maintain viral suppression for as long as bNAb levels remain therapeutic. Furthermore, post-treatment control for 48 weeks and longer was observed in 12% of the study cohort. We are evaluating the immunomodulatory effects on the size and composition of the latent reservoir.

Basic Science:

(E) HIV Reservoirs, Latency, and Curative Strategies Including Therapeutic Vaccines and Gene Therapy 

Search Terms:

HIV
HIV cure research
HIV latency
Immunotherapy
Broadly neutralizing antibody

Supporting Image: Abstract_Fig.jpg
 

Does this abstract include any aspects of research on SARS-CoV-2 or COVID-19?

No

Is this abstract a case report, meta-analysis, or systematic review?

No