A characterization of HIV intra-host evolution spanning its foundational forces and their translational implications

Abstract

HIV's rapid evolutionary rate has proven a longstanding challenge to developing new treatment modalities and vaccinations. In this work, I first investigate how the rate of recombination, a primary driving force of evolution, can vary alongside intra-host viral demography. By developing a new method for estimating recombination rates, I show that HIV's recombination rate appears to be density dependent and is positively associated with viral load in intra-host viral populations. Then, I investigate how this rapid evolutionary rate allows HIV to escape from broadly neutralizing antibody (bNAb) treatments. I show that HIV escapes from two different bNAbs via distinct modes of evolution, based on how each bNAb targets the virus, and that in both cases many different viruses escape concurrently. Lastly, I find that the high number of distinct escaping viruses allows intra-host HIV populations to maintain their pre-treatment diversity and linkage levels even as escape variants sweep to high frequencies, upending traditional selective sweep signatures. Altogether, these discoveries further our understanding of the basic processes underpinning HIV evolution as well as their evolutionary and translational implications.