Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART

Wan C, Bachmann N, Mitov V, Blanquart F, Céspedes S P, Turk T, Neumann K, Beerenwinkel N, Bogojeska J, Fellay J, Roth V, Böni J, Perreau M, Klimkait T, Yerly S, Battegay M, Walti L, Calmy A, Vernazza P, Bernasconi E, Cavassini M, Metzner K J, Günthard H F, Kouyos R D, & the Swiss HIV Cohort Study 2020. Nat. Commun.
PDF
2020-wan-natcommun.pdf
Supplement
2020-wan-natcommun-suppl.pdf
DOI
10.1038/s41467-020-19198-7

Abstract

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients’ hurdle towards a cure.