HIV Competition Dynamics over Sexual Networks: First Comer Advantage Conserves Founder Effects

Outside Africa, the global phylogeography of HIV is characterized by compartmentalized local epidemics that are typically dominated by a single subtype, which indicates strong founder effects. We hypothesized that the competition of viral strains at the epidemic level may involve an advantage of the resident strain that was the first to colonize a population. Such an effect would slow down the invasion of new strains, and thus also the diversification of the epidemic. We developed a stochastic modelling framework to simulate HIV epidemics over dynamic contact networks. We simulated epidemics in which the second strain was introduced into a population where the first strain had established a steady-state epidemic, and assessed whether, and on what time scale, the second strain was able to spread in the population. Simulations were parameterized based on empirical data; we tested scenarios with varying levels of overall prevalence. The spread of the second strain occurred on a much slower time scale compared with the initial expansion of the first strain. With strains of equal transmission efficiency, the second strain was unable to invade on a time scale relevant for the history of the HIV pandemic. To become dominant over a time scale of decades, the second strain needed considerable (>25%) advantage in transmission efficiency over the resident strain. The inhibition effect was weaker if the second strain was introduced while the first strain was still in its growth phase. We also tested how possible mechanisms of interference (inhibition of superinfection, depletion of highly connected hubs in the network, one-time acute peak of infectiousness) contribute to the inhibition effect. Our simulations confirmed a strong first comer advantage in the competition dynamics of HIV at the population level, which may explain the global phylogeography of the virus and may influence the future evolution of the pandemic.Author Summary: The African epicentre of the HIV pandemic is home to a vast array of divergent viruses; however, local epidemics in other parts of the world are typically dominated by a single variant (subtype) of the virus, with different subtypes found in the different regions. This pattern indicates that local epidemics outside Africa have been started by the introduction of single “founder” viruses in the susceptible populations. However, how these patterns persisted over several decades in the face of international migration requires further explanation. By analyzing simulated epidemics, we demonstrated that an epidemic established by the first successful founder strain can inhibit the introduction and slow down the subsequent spread of further virus strains by several mechanisms of interference. Our results have implications for the global evolution of the HIV pandemic: the fast expansion of subtypes benefited from a “first comer advantage,” and founder viruses may have been selected by random sampling, rather than due to superior transmissibility/fitness; the fast expansion of these (possibly) suboptimal virus strains may have considerably delayed the spread of more transmissible HIV variants; however, the future evolution of the pandemic is likely to be characterized by a slow expansion of viral strains with increased transmission potential.