Computationally Developed Cocktail for HIV Therapy Significantly Reduces Chance of Viral Rebound

Cocktails of broadly neutralizing antibodies (bNAbs) developed by computational methods could be an effective new tool to treat or cure HIV and rapidly evolving pathogens, according to the results of a study published in eLife.¹ By selecting specific combinations of bNAbs that analyze virus’ genetics, computer-based cocktails could make HIV treatment more effective.¹

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

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

A genetically diverse virus HIV mutates as it rapidly copies itself, and the virus copies itself at a rate faster than the immune system’s antibodies can respond, which reduces the antibodies’ ability to target new strains of the virus.²

“Leveraging 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 broad 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-evolving HIV virus have survived treatment and rebounded in the blood.¹

Using high-throughput sequencing, LaMont and colleagues analyzed 10 years of data on HIV virus genetics from 11 untreated HIV patients to determine which HIV strains were likely to evade bNAb treatment, and whether the strain mutation was associated with survival cost. ¹ They applied these findings to 3 real-life trials to determine which bNAb combinations could best inhibit viral escape.¹

The study authors noted that bNAbs 10-1074 can protect against diverse HIV populations because the mutated virus cannot survive as well.¹ Additionally, PGT121 was found to be effective against less diverse populations who rarely escape bNAb antibodies.¹ Ultimately, the investigators found that a cocktail of PGT121, VRC01, and PG9 proved to be the optimal combination of bNAbs, reducing the chance of viral rebound to less than 1%.¹

“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,” Nourmohammad said in the press release.¹ “Our approach may also be useful for designing therapies against other rapidly evolving agents that cause disease, such as the Hepatitis C virus, drug-resistant bacteria, or cancer tumour cells.”¹

References

• Novel HIV combination therapies could prevent viral escape 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%20broadly,study%20published%20today%20in%20eLife
• Snow B. The Rise of Broadly Neutralizing Antibodies. AVAC website. May 17, 2018. Accessed July 20, 2022. https://www.avac.org/blog/rise-broadly-neutralizing-antibodies