Imagine two drugs — A and B. When treated with drug A, most patients become resistant rapidly. When treated with drug B, only a few patients become resistant. In hindsight, it's easy to tell which is which — simply count the number of patients who have become resistant to the disease.
But what if there was a way to tell which drugs would fail due to widespread resistance before treating hundreds or thousands of patients?
Now there may be, thanks to an effort led by Stanford graduate student Alison Feder that was published recently in eLife. A Stanford news release highlights the research.
The team of researchers examined data from 6,717 HIV patients spanning from the early days of the epidemic until recently. They knew what happened: In the early days, most patients became resistant. More recently, just a few patients did.
They tapped the data to see if it held clues about the outcome — could they glean insights about the likelihood of developing resistance by examining the genomes of viruses themselves?
The answer, the researchers found, was yes. Viral samples from the early days of the epidemic — when resistance was everywhere — showed great diversity in each patient. That is, each person infected harbored a diverse viral population even after they had developed resistance to the drug. Mutations conferring resistance had popped up repeatedly and independently in a variety of viral genomes.
In contrast, in more recent cases where resistance had developed (few and far between), the viral diversity within each resistant patient was quite small. These drugs were vulnerable to only a few viral mutations, so when one developed, it was one of the only surviving viral genomes in that patient.
Feder is pleased with the outcome. "It's an exciting potential application," she says in the release, noting that the work could be helpful in drug development for other diseases. "We're using data in a way that people haven't looked at it before."
Previously: Growing resistance to vital HIV drug raises concern, Excessive antibiotic use in flu season contributes to resistance and Spread of drug-resistant HIV in Africa and Asia is limited, Stanford research finds
Photo by Melly95