Mapping a Moving Target

Research question
It is well known that HIV mutates within each person living with the virus, in part to escape pressure from that person’s immune system and from antiretroviral therapy. HIV also mutates because the mechanisms by which it replicates are very error-prone, particularly with regard to formation of its outer envelope—the very site targeted by new cure interventions, including neutralizing antibodies and CAR T cells.

For its ability to change rapidly and randomly, some scientists have called HIV a “moving target.” But what if researchers could more accurately predict and anticipate these mutations with an eye to developing more targeted interventions?

Findings
Scientists at the University of Iowa and Iowa State University used sophisticated mathematical modeling tools to interrogate the amino acid sequences of envelopes from 300 people living with HIV. For each person, the variability of these amino acids was mapped onto the three-dimensional structure of the HIV envelope. An algorithm was developed that predicted the variability of regions currently being targeted by multiple treatments, and did so with a greater fidelity than available modeling tools.

Impact
The authors conclude that their system may serve as “the basis for personalizing antiviral therapeutics,” not only for HIV but for other infections as well.

amfAR’s role
amfAR was a funder of this research. Authors of this paper include amfAR grantee Dr. Hillel Haim.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/37337202

Dr. Laurence is amfAR’s senior scientific consultant.

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