Combination bNAb’s sustain viral suppression for 40 weeks: phase 1 results

Kirk Taylor, HIV i-Base

A combination of two broadly-neutralising antibodies (bNAbs) – 3BNC117 and 10-1074 – maintained undetectable viral load after interrupting ART for over 40 weeks. [1]

This paper was published in 1 June 2022 edition of Nature reported on two studies run from September 2018 to January 2021. The first was a randomised placebo-controlled study in 14 participants already suppressed on ART that had been started during acute infection. A second open-label study was in five treatment naive participants. Neither study screened participants for sensitivity to the bNAbs.

Participants were randomised 1:1 to bNAb’s or placebo (Group 1); or enrolled in the open label study (Groups 2). All participants were male, 12/19 were white and median age was 39 (range: 27 to 57).

Median baseline CD4 counts were 799 cells/mm³ (range: 543 to 1,177) vs 612 cells/mm³ (426 to 832) in the active vs placebo arms; and 640 cells/mm³ (540 to 1,1011) in Group 2 where viral load ranged from 200 to 5,000 copies/mL

Participants received bNAbs across 8 infusions: twice in month 1 and then monthly for 6 months, ART was stopped three days after the first infusion.

Those receiving bNAbs in group 1 were off ART for a median of 39.6 weeks (range 9.9 to 49.6). Median viral suppression for 40% of group 2 participants was 41.7 weeks. In Group 1, ART was restarted for 6 out of 7 participants in the placebo group before week 28 (median 9.4 weeks; range 5.3 to 26).

Longitudinal measurements did not indicate a reduction HIV reservoir in participants that received bNAbs. Participant CD4 counts did however remain stable across the study period.

comment

Although ART is highly effective, stopping treatment usually leads to rapid viral rebound often within two weeks . Early results using bNAbs have included the potential to maintain viral suppression off-ART.

3BNC117 and 10-1074 are promising bNAb therapies that target the CD4 binding site and V3 loop of the HIV, respectively. Previous studies have also reported sustained suppression off ART. [2, 3]

Of note, both antibodies are older formulations, with more recent LC variants now providing significantly longer half-lives, with a single infusion expected to last more than 16 weeks.

The long-acting formulations of these bNAbs are included in the UK RIO study that is currently recruiting in London and Brighton and shortly begin in Manchester. [4]

References

1. Sneller MC et al. Combination anti-HIV antibodies provide sustained virological suppression. Nature. https://doi.org/10.1038/s41586-022-04797-9  (01 Jun 2022).
   https://www.nature.com/articles/s41586-022-04797-9
2. Mendoza P et al. Combination therapy with anti HIV-1 antibodies maintains viral suppression. Nature. https://doi.org/10.1038/s41586-018-0531-2 (26 Sep 2018)
   https://www.nature.com/articles/s41586-018-0531-2 
3. Jefferys R. CROI 2022: targeting reservoir with ART + bNAb 3BNC117 + romidepsin maintained undetectable viral load off-ART for 3.7 years in one case. (HTB 01 Mar 2022).
   https://i-base.info/HTB/42209
4. The RIO study.
   https://riotrial.org