medRxiv preprint doi: https://doi.org/10.1101/2020.12.07.20245480; this version posted December 8, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . Evolution during primary HIV infection does not require adaptive immune selection David A Swan1, Morgane Rolland2,3, Joshua Herbeck4, Joshua T Schiffer1,5,6, Daniel B Reeves*1. 5 *corresponding author:
[email protected] 1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle WA, USA 2U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA 10 3Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA 4Department of Global Health, University of Washington, Seattle WA, USA 5Department of Medicine, University of Washington, Seattle WA, USA 6Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle WA, USA 15 Abstract: Modern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic (wi-phy) models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The most parsimonious and accurate model required no positive selection, suggesting that the host adaptive immune system reduces viral load, but 20 does not drive observed viral evolution. Rather, random genetic drift primarily dictates fitness changes. These results hold during early infection, and even during chronic infection when selection has been observed, viral fitness distributions are not largely different from in vitro distributions that emerge without adaptive immunity.