Based on the genetics of the virus, a computer-based method might assist clinicians in choosing the most effective combinations of broadly neutralising antibodies to treat HIV.
According to a study that was just published in eLife, carefully formulated combinations of broadly neutralising antibodies (bNAbs) could help treat HIV while reducing the chance that the virus would evade therapy.
Accordingly, computational methods for choosing bNAb combinations based on viral genetics may aid in preventing viral escape and increase the efficacy of HIV treatment. It might also provide a method for creating potent bNAb combinations to tackle other rapidly developing diseases.
A potentially effective new treatment option for illnesses caused by quickly changing viruses like HIV is provided by bNAbs. Clinical studies treating HIV with a single bNAb have revealed that some viral strains may resist the medication and cause a resurgence of the virus in the blood. Combinations of bNAbs may potentially be a more effective strategy, but it can be difficult to determine which combinations work best.
They examined the genomes of HIV viruses gathered over a 10-year period from 11 HIV-positive patients who were not receiving treatment using high-throughput sequencing. Using this information, the scientists made predictions about which virus strains could be able to resist therapy. After that, they used the knowledge to foretell viral rebounds in three actual bNAbs trials.
The team’s computational method was then used to identify a set of bNAbs that is least likely to allow any virus to escape. Additionally, they discovered that particular bNAbs, such 10-1074, are more effective against a variety of virus populations because alterations that allow viruses to escape also decrease the likelihood that the virus would survive. Due to the rarity of mutations that allow escape, others, such as PGT121, are more effective against viral populations that are less varied. Overall, the findings indicated that PG9, PGT151, and VRC01 are the three bNAbs that work best together.
“We’ve shown the combination of PG9, PGT151 and VRC01 reduces the chance of viral rebound to less than 1%,” LaMont says. “It does this by targeting three different regions of the virus’ protective outer wrapping, or envelope.”
“Combining bNAbs, administered via intravenous infusion every few months, with current antiretroviral therapies (ART) that require daily doses could further improve long-term HIV treatment success,” suggests senior author Armita Nourmohammad, Assistant Professor in the Department of Physics at the University of Washington, Seattle
ART limits the genetic variety of the viral population and lowers the probability of the formation of bNAb escape variants by decreasing HIV’s capacity to proliferate and produce new variants.
More research, according to the authors, is required to verify any potential advantages of combining ART and bNAbs.