Abstract
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.
Highlights
The evolution of parasites in response to human interventions is a fundamental challenge to public health
| 305 support for the prediction that imperfect drugs and vaccines can lead to the evolution of higher virulence (e.g., Barclay et al, 2012; Gandon & Day, 2008; Read et al, 2015; Schneider et al, 2012), and HIV-1 conforms to the conditions necessary for this kind of evolution (Gandon et al, 2001): it is an obligate endoparasite; its virulence and transmission both increase with viral density; and its medical interventions imperfectly reduce viral replication and susceptibility to infection
Our approach contrasts with a recent individual-based simulation study, which predicts the transient evolutionary dynamics of HIV virulence in response to ART (Herbeck et al, 2016), we recapitulate their principal finding that fully suppressive antiretroviral therapy (ART) favours the transmission of higher set-point viral load (SPVL) strains under a test and treat policy
Summary
The evolution of parasites in response to human interventions is a fundamental challenge to public health. In addition to conventional resistance mechanisms (e.g., efflux pumps to thwart drugs or antigenic variation to escape vaccine-induced immunity), experiments have shown that parasite virulence can evolve in response to—and mitigate the effects of—medical interventions, as exemplified by Marek’s disease virus in response to vaccines (Read et al, 2015), and rodent malaria parasites in response to drugs (Schneider et al, 2012) and vaccines (Barclay et al, 2012) The extent of this kind of evolution in nonexperimental systems is poorly understood, but there. PrEP differs from traditional anti-infection vaccines in an important way: if a host on PrEP becomes infected, the viruses they harbour will immediately be exposed to antiretroviral drugs For this reason, PrEP may be expected to increase the strength of selection in response to ART. We examine the net epidemiological and clinical effects of interventions when SPVL evolves
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
