Modelling the evolution of HIV‐1 virulence in response to imperfect therapy and prophylaxis

Average HIV‐1 virulence appears to have evolved in different directions in different host populations since antiretroviral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virul...

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Bibliographic Details
Published in:Evolutionary applications 2017-03, Vol.10 (3), p.297-309
Main Authors: Smith, David R. M., Mideo, Nicole
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
adaptive dynamics
AIDS
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Disease
Disease prevention
Epidemiology
Evolution
HIV
Human immunodeficiency virus
Infections
Lentivirus
Original
Pandemics
Parasites
pre‐exposure prophylaxis
Prophylaxis
Public health
Retroviridae
set‐point viral load
Virulence
virulence evolution
Viruses
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Summary:Average HIV‐1 virulence appears to have evolved in different directions in different host populations since antiretroviral therapy first became available, and models predict that HIV drugs can select for either higher or lower virulence, depending on how treatment is administered. However, HIV virulence evolution in response to “leaky” therapy (treatment that imperfectly suppresses viral replication) and the use of preventive drugs (pre‐exposure prophylaxis) has not been explored. Using adaptive dynamics, we show that higher virulence can evolve when antiretroviral therapy is imperfectly effective and that this evolution erodes some of the long‐term clinical and epidemiological benefits of HIV treatment. The introduction of pre‐exposure prophylaxis greatly reduces infection prevalence, but can further amplify virulence evolution when it, too, is leaky. Increasing the uptake rate of these imperfect interventions increases selection for higher virulence and can lead to counterintuitive increases in infection prevalence in some scenarios. Although populations almost always fare better with access to interventions than without, untreated individuals could experience particularly poor clinical outcomes when virulence evolves. These findings predict that antiretroviral drugs may have underappreciated evolutionary consequences, but that maximizing drug efficacy can prevent this evolutionary response. We suggest that HIV virulence evolution should be closely monitored as access to interventions continues to improve.
ISSN:1752-4571
1752-4571
DOI:10.1111/eva.12458