Anti-HIV Antibody Combination Leads to Long-term HIV Suppression, Researchers Find

People living with HIV (PLWH) achieved long-term virological suppression after receiving 2 broadly neutralizing anti-HIV antibodies (bNAbs) and ceasing antiretroviral therapy (ART), according to newly published results.

These findings are part of a small study published in Nature and, according to the study authors, suggest that combination bNAb therapy may be a potential alternative to daily ART for PLWH in the future.

However, it should be noted that the first part of the study included only an all-male and mostly White sample of 14 PLWH who started ART during the early phase of HIV infection.

Oral ART is highly effective at suppressing HIV viral load and can nearly completely suppress the level of plasma viremia in most PLWH. However, like any daily oral medication, many people struggle to fully adhere to their ART regimen.

Long-term medication use may also result in long-term adverse effects and a more drug-resistant virus. Partly due to the development of bNAb-resistant HIV in a person living with HIV, prior studies have demonstrated that a single bNAb had limited success in suppressing HIV viral load.

In an effort to address this issue, the authors tested a combination of 2 bNAbs, 3BNC117 and 10-1074, that target different parts of the HIV Env glycoprotein. The former bNAb binds to the CD4-binding site, whereas the latter targets the V3 loop and surrounding glycans.

They report results of a dual-component clinical trial conducted between September 2018 and January 2021. The first part included 14 PLWH who began receiving ART during the early stage of their HIV. These participants were randomized to receive either a first infusion of the combination bNAbs or placebo, and they were then taken off antiretrovirals.

Participants then received up to 8 infusions of the bNAbs or placebo over 24 weeks. The authors measured HIV levels and CD4 T-cell counts every 2 weeks.

For up to 28 weeks post infusion, none of the 7 patients who received the bNAb infusion had to restart ART. Meanwhile, 6 of the 7 participants in the placebo group had to begin ART again. The median duration of time off ART was 39.6 weeks for the bNAb group and 9.4 weeks for the placebo group.

The second component of this study was an open-label study with 5 PLWH with viremic control who were ART naive and had baseline plasma viremia levels between 200 and 5000 copies per mL. Only 2 of the 5 participants maintained complete HIV suppression for 41.7 weeks, on average, following bNAb transfusion.

The authors concluded that this dual bNAb transfusion therapy may be highly effective at suppressing HIV levels for prolonged periods in PLWH not receiving ART, as long as they have not developed an antibody-resistant virus.

“As the next generation of bNAbs with increased breadth and prolonged half-lives (>60 days) become available, there is a reason to believe that the infrequent administration (that is, twice a year) of such antibodies, possibly along with a long-acting injectable antiretroviral drug, could lead to ART-free HIV suppression for extended periods (years) in individuals with infection,” the authors concluded.

Reference

Sneller MC, Blazkova J, Justement JS, et al. Combination anti-HIV antibodies provide sustained virological suppression. Nature. Published online June 1, 2022. doi:10.1038/s41586-022-04797-9