CROI 2022: Targetting reservoir with ART + bNAb 3BNC117 + romidepsin maintained undetectable viral load off-ART for 3.7 years in one case

Richard Jefferys, TAG

During the CROI session on HIV cure research, Ole Søgaard presented results from the “eClear” trial, which investigated the broadly neutralising antibody (bNAb) 3BNC117 and a candidate latency-reversing agent, romidepsin. [1]

The study enrolled 60 participants, approximately half with recent HIV infection (less than 6 months), and randomly assigned them to one of four groups.

1. ART alone.
2. ART plus 3BNC117 at day 7 and 21 after ART initiation.
3. ART plus romidepsin at day 10, 17 and 24.
4. ART plus 3BNC117 and romidepsin (administered at the same times listed above).

The primary aim was to assess if administering these interventions around the time of ART initiation could accelerate clearance of the HIV reservoir and promote control of HIV viral load after an analytical treatment interruption (ATI) a year later.

The rationale derived from a study demonstrating that the persistent HIV reservoir is formed close to the time of ART initiation in a substantial proportion of people with HIV. [2]

Participants were followed for a year and then given the option of undergoing a 12-week analytical treatment interruption (ATI) at day 400 of follow up. The majority of participants were white men; a total of five women were enrolled but none were randomized to receive 3BNC117.

Receipt of 3BNC117 was associated with greater declines in levels of cells expressing HIV RNA and the HIV p24 protein, as well as increases in HIV-specific CD8 T cell responses. Furthermore, four out of the five participants whose pre-ART HIV samples were fully sensitive to 3BNC117 (i.e. no evidence of resistance to the anti-HIV effects of the antibody) maintained HIV viral load below 5,000 copies/mL throughout the 12-week ATI, compared to three of 15 participants who had pre-ART evidence of HIV resistance to 3BNC117 or did not receive the antibody. These effects appeared independent of receipt of romidepsin.

One participant from the 3BNC117 and romidepsin group still remains off ART and has maintained undetectable HIV viral load for 3.7 years and counting. In the Q&A session after his talk, Søgaard noted that the HIV reservoir in this individual (as measured by an intact proviral DNA assay) is continuing to shrink in size over time.

Additional information on the association between 3BNC117 and improved CD8 T cell responses will be presented at CROI tomorrow by Míriam Rosás-Umbert (embargoed when this report was posted). [3]

The results indicate that bNAbs like 3BNC117 may have the potential to enhance clearance of the HIV reservoir and promote containment of viral load after treatment interruption. Additional ongoing studies involving combinations of bNAbs and ATIs, such as the RIO trial, should shed further light on the efficacy of the approach. [4]

Combinations of bNAbs may be necessary to circumvent the problem of baseline HIV resistance to individual antibodies.

Links to the relevant CROI abstract pages are below – the abstract text and presentation webcasts will become available on these pages in around 30 days (at the current time access is restricted to conference registrants).

Source

Jefferys R. CROI 2022 Update: A new potential HIV cure case; broadly neutralising antibody enhances post-treatment control. TAG basic Science Blog. (15 February 2022)
https://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2022/02/croi-2022-update-a-new-potential-hiv-cure-case-broadly-neutralizing-antibody-enhances-post-treatment.html

References

1. Gunst JD et al. The Impact of 3BNC117 and romidepsin treatment at ART initiation on HIV-1 persistence. CROI 2022, 12–16 and 22–24 February, virtual meeting. Oral abstract 62.
   https://www.croiconference.org/abstract/the-impact-of-3bnc117-and-romidepsin-treatment-at-art-initiation-on-hiv-1-persistence (abstract)
2. Abrahams MR et al. The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation. Sci Transl Med. 2019 Oct 9;11(513):eaaw5589. doi: 10.1126/scitranslmed.aaw5589.
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233356
3. Rosás-Umbert M et al. Administration of 3BNC117 at ART initiation induces long-term HIV CD8 T-cell immunity. CROI 2022, 12–16 and 22–24 February, virtual meeting. Oral abstract 62.
   https://www.croiconference.org/abstract/administration-of-3bnc117-at-art-initiation-induces-long-term-hiv-cd8-t-cell-immunity (abstract)
4. UK RIO Study.
   https://riotrial.org]

This report was first published on 16 February 2022.