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Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART
Journal
Nature Communications
Volume
11
Number
1
Pages / Article-Number
5542
Mesh terms
Adult; Anti-Retroviral Agents, pharmacology; CD4-Positive T-Lymphocytes, virology; Cohort Studies; DNA, Viral, genetics; Female; Genome, Viral; HIV Infections, virology; HIV-1, drug effects, genetics; Humans; Male; Time Factors; Viral Load
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.
