Computer-developed cocktail for HIV treatment dramatically reduces risk of viral rebound

Using computational methods, the development of an HIV therapeutic cocktail based on the genetics of the virus has been shown to increase treatment efficacy.

According to the results of a study published in eLife.1 By selecting specific combinations of bNAbs that analyze the genetics of the virus, computerized cocktails could make HIV treatment more effective.1

Specifically, the use of computational methods could help concoct unique combinations of bNAbs to effectively treat other rapidly evolving pathogens.1

“For our study, we proposed to use a computational approach to predict the efficacy of bNAb combinations based on HIV genetics,” said Colin LaMont, PhD, a researcher at the Max Planck Institute for Dynamics and Health. self-organization in Göttingen, Germany. A press release.1

A genetically diverse virus HIV mutates when it copies itself rapidly, and the virus copies itself at a faster rate than the antibodies in the immune system can respond, reducing the ability of the antibodies to target new strains of the virus.2

“Harnessing genetic data can help us design more effective HIV therapies [to target the virus]said Armita Nourmohammad, PhD, MS, assistant professor in the Department of Physics at the University of Washington, Seattle, in the press release.1

Scientists first discovered 4 rare antibodies in the 1990s that could neutralize a wide range of HIV strains (bNAbs), and dozens more bNAbs have since been identified.2 Clinicians have conducted trials with single bNAbs, but some strains of the ever-changing HIV virus have survived treatment and rebounded in the blood.1

Using high-throughput sequencing, LaMont and colleagues analyzed 10 years of HIV virus genetic data from 11 untreated HIV patients to determine which strains of HIV were likely to evade bNAb treatment and whether strain mutation was associated with cost of survival. 1 They applied these results to 3 real-world trials to determine which combinations of bNAbs might best inhibit viral evasion.1

The study authors noted that bNAbs 10-1074 may protect against various populations of HIV because the mutated virus cannot survive equally.1 Additionally, PGT121 has been shown to be effective against less diverse populations that rarely escape anti-bNAb antibodies.1 Ultimately, the researchers found that a cocktail of PGT121, VRC01, and PG9 proved to be the optimal bNAb combination, reducing the risk of viral rebound to less than 1%.1

“Combining bNAbs, given by intravenous infusion every few months, with current antiretroviral therapies (ART) that require daily doses could further improve long-term HIV treatment success,” Nourmohammad said in the press release.1 “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 cancerous tumor cells.”1

References

  • New HIV combination therapies could prevent viral leakage and rebound. ELIFE; July 19, 2022. Accessed July 20, 2022. https://www.eurekalert.org/news-releases/959236#:~:text=Novel%20HIV%20combination%20therapies%20could%20prevent%20viral%20escape%20and%20rebound&text =Carefully%20designed%20cocktails%20of%20widely,%20study%20published%20today%20in%20eLife
  • Snow B. The rise of largely neutralizing antibodies. AVAC website. May 17, 2018. Accessed July 20, 2022. https://www.avac.org/blog/rise-broadly-neutralizing-antibodies

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