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

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.

A phylogenomic analysis of Marek's disease virus reveals independent paths to virulence in Eurasia and North America

“…Data from a recent study show that newer MDV lineages that evolved in the vaccination era are significantly fitter than ancestral vaccine‐naïve strains (Read et al., ). These findings support theoretical predictions (Gandon et al., ; Smith & Mideo, ) that the use of vaccines to suppress but not block pathogen replication or transmission (so called antidisease, imperfect, or leaky vaccines) results in the evolution of viruses with increased replication (i.e., fitness) or transmission and therefore virulence. Meanwhile, previous studies addressing the industrialization of farming have discussed how MDV virulence can increase independently of vaccine use (Atkins, Read, Walkden‐Brown et al., ; Atkins, Read, Savill et al., ; Rozins & Day, ).…”

Modeling the immunological pre-adaptation of HIV-1

“…First, the potential of HIV-1 for preadaptation might negatively impact the long-term success of promising HIV-1 vaccines that are currently under development [3]. Second, the risk that HIV-1 virulence increases as antiretroviral treatment becomes more widely available might be limited, contrary to previous model predictions [38,78].…”

The impact of HIV-1 within-host evolution on transmission dynamics

“…PrEP has been highly effective in reducing HIV-1 incidence[68], although a PreP failure was recently documented despite good adherence[69]. This raises important concerns with respect to the propagation of transmitted drug resis-175 tance and the amplification of virulence evolution[70,71].Furthermore, transmission fitness has been linked to the similarity of the T/F virus to the HIV-1 (subtype) consensus sequence among infected individuals 7…”