Title

Combining immunotherapeutic agents to achieve ARV-free remission of HIV

Code

SY20

Session Type

Symposium

Track

Track A: Basic and translational science

Format

Hybrid

CME accreditation

Yes

ROOM/CHANNEL

Room 517d/Channel 2

Date Time

31 July 14:15 - 15:15

Moderators

Thumbi NDUNG'U, Africa Health Research Institute, University of KwaZulu-Natal, South Africa
Katherine J. BAR, Penn Centre for AIDS Research, United States

While individual therapeutic modalities (such as therapeutic vaccination, broadly neutralizing antibody or bNAb infusion, inhibition of immunosuppressive pathways, potentiation of immunostimulatory pathways and HIV latency reversal agents) are being explored for their capacity to induce control of HIV, mounting evidence suggests that durable remission of HIV may require a combination of agents. This session will highlight different strategies for combining therapeutic modalities to achieve antiretroviral-free remission of HIV.

14:15 2 min	Introduction Thumbi NDUNG'U, Africa Health Research Institute, University of KwaZulu-Natal, South Africa Katherine J. BAR, Penn Centre for AIDS Research, United States

14:17 15 min	Combination therapies with bNAbs Marina CASKEY, The Rockefeller University, United States	Slides

14:32 15 min	Combinations to reprogramme CD8+ T cells Asier SAEZ-CIRION, Institut Pasteur, France	Slides

14:47 15 min	Combination therapies in non-human primates Afam OKOYE, Oregon Health and Science University, United States	Slides

15:02 13 min	Q&A Thumbi NDUNG'U, Africa Health Research Institute, University of KwaZulu-Natal, South Africa Asier SAEZ-CIRION, Institut Pasteur, France Afam OKOYE, Oregon Health and Science University, United States Marina CASKEY, The Rockefeller University, United States Katherine J. BAR, Penn Centre for AIDS Research, United States

AUTHOR

Paula Grasberger

SUMMARY

This session featured data on strategies to achieve ARV-free remission using broadly neutralizing antibodies (bNAbs), CD8+ T cell reprogramming, and PD-1 blockade.

HIGHLIGHTS

Dr. Marina Caskey (Rockefeller University) reported data from a phase 1b trial of repeated dosing with two bNAbs (10-1074 and 3BNC117) upon ART interruption (Gaebler et al. Nature 2022). In patients not screened for bNAb sensitivity, this regimen showed improved time to viral rebound as compared placebo. Post-hoc analysis of bNAb sensitivity using phenotypic (PhenoSense) and genotypic (env sequencing, Q4PCR) assays showed that neither reliably predicted clinical outcomes. It was also shown that treatment with both bNAbs could reduce the viral reservoir over 6 months, and that T cell responses were improved during bNAb therapy following ART discontinuation. Dr. Asier Saez-Ciron (Institut Pasteur) showed that treatment with a GSK3 inhibitor (BIO) reprogrammed CD8+ T cells towards more stemness, allowing them to maintain a memory-like phenotype following stimulation. The treated cells also maintained effector properties, enhanced HIV suppression, expressed more IL-7 and IL-15 receptors, and showed a long-term survival capacity. Dr. Afam Okoye (Oregon Health and Science University) presented data from primate studies showing that CD8+ T cell responses are not sufficient to control viral rebound following ART interruption. Furthermore, neither treatment with anti-PD-1, nor anti-CD20 treatment to enhance CD8+ T cell responses improved their control of HIV-1 rebound.

CRITICAL ASSESSMENT

Treatment with 10-1074 and 3BNC117 showed promising increases in viral suppression following ART interruption, and reduced the intact proviral reservoir. Reprogramming of CD8+ T cells towards a stem-like phenotype using GSK3 inhibition in vitro enhanced their ability to suppress HIV, and conferred maintenance of effector properties and long-term survival capacity. Reproducing these results in an animal model will help to confirm their relevance. PD-1 blockade and anti-CD20 treatment of NHPs did not enhance CD8+ T cell responses to HIV-1 viral rebound, highlighting the detrimental effects of a lagging immune response to rapid viral replication.