Carefully designed cocktails of broadly neutralizing antibodies (bNAbs) can help treat HIV while reducing the risk of the virus escaping treatment, suggests a study published today in eLife.
The study showed that computational approaches to selecting combinations of bNAbs based on viral genetics can help prevent viral escape, making HIV treatment more effective. It may also provide a strategy for designing effective combinations of bNAbs for the treatment of other rapidly evolving pathogens.
BNAbs offers a great new tool to treat or possibly cure infections with fast-growing viruses such as HIV. Clinical trials using a bNAb to treat HIV have shown that certain strains of the virus can survive treatment and lead to the return of the viruses in the blood. Combinations of bNAbs may be a more effective method, but finding the best combinations is a challenge.
“For our study, we proposed the use of a computational method to predict the effectiveness of bNAb combinations based on HIV genetics,” said Colin LaMont, a researcher at the Max Planck Institute for Dynamics and Self -Organization in Göttingen, Germany.
LaMont and colleagues used high-throughput sequencing to analyze the genetics of HIV virus collected over 10 years from 11 untreated HIV patients. The team used this data to determine which viral strains could survive the treatment of different bNAbs and whether dodging bNAbs was related to survival costs. Next, using computational methods, they applied the knowledge gained to predict viral rebounds in three real -life trials of bNAbs.
Finally, the team used their computational approach to find a combination of bNAbs that were the least allowed to escape any virus. They also found that some bNAbs, such as 10–1074, were better against different populations of viruses because the mutations that allowed the viruses to survive also made the virus less viable. Others, including PGT121, are more effective against less diverse viral populations because mutations that enable escape are rare. Overall, the results suggest that the optimistic combination includes three bNAbs: PG9, PGT151 and VRC01.
“We showed a combination of PG9, PGT151 and VRC01 that reduced the chance of viral rebound to less than 1%,” LaMont said. “It does this by targeting three different regions of protection on the outer envelope of the virus, or envelope.”
“Combining bNAbs, administered by intravenous infusion every few months, with current antiretroviral therapies (ART) that require daily doses may further improve the long-term success of HIV treatment,” suggests senior author Armita Nourmohammad, Assistant Professor in the University’s Department of Physics. in Washington, Seattle.
ART reduces the ability of HIV to reproduce and produce new variants, limiting the genetic diversity of the viral population and lowering the likelihood of the emergence of bNAb escape variants. The authors say that more studies are needed to confirm the potential benefits of combining ART and bNAbs.
“Our study shows that the use of genetic data can help us design more effective HIV therapies,” Nourmohammad concludes. “Our approach may also be useful for designing therapies against other rapidly evolving disease-causing agents, such as the Hepatitis C virus, drug-resistant bacteria, or tumor cells. cancer. “
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