Abstract
Evolutionary theory hypothesizes that intermediate virulence maximizes pathogen fitness as a result of a trade-off between virulence and transmission, but empirical evidence remains scarce. We bridge this gap using data from a large and long-standing HIV-1 prospective cohort, in Uganda. We use an epidemiological-evolutionary model parameterised with this data to derive evolutionary predictions based on analysis and detailed individual-based simulations. We robustly predict stabilising selection towards a low level of virulence, and rapid attenuation of the virus. Accordingly, set-point viral load, the most common measure of virulence, has declined in the last 20 years. Our model also predicts that subtype A is slowly outcompeting subtype D, with both subtypes becoming less virulent, as observed in the data. Reduction of set-point viral loads should have resulted in a 20% reduction in incidence, and a three years extension of untreated asymptomatic infection, increasing opportunities for timely treatment of infected individuals.
Highlights
To spread, a pathogen must multiply within the host to ensure transmission, while simultaneously maintaining opportunities for transmission by avoiding host morbidity or death (Anderson and May, 1982; Alizon et al, 2009)
We focused on one of the longest established generalised HIV epidemics, in rural Uganda, and used data collected as part of the Rakai Community Cohort Study (RCCS), a large and long-standing population-based open cohort conducted by the Rakai Health Sciences Program (RHSP) in Rakai District
As in other HIV epidemics, we found that set-point viral load (SPVL) is highly variable in this population, with values ranging from 102 copies/mL to 107 copies/mL
Summary
A pathogen must multiply within the host to ensure transmission, while simultaneously maintaining opportunities for transmission by avoiding host morbidity or death (Anderson and May, 1982; Alizon et al, 2009). This creates a trade-off between transmission and virulence. The transmission potential of a parasite is the product of the transmission rate and the time during which the host is alive and can transmit The latter is approximately the time to AIDS in HIV as host death occurs shortly after the onset of AIDS and sexual activity may be reduced in the AIDS phase because of AIDS-associated symptoms (Hollingsworth et al, 2008). Since many persons at risk of infection do not routinely obtain HIV testing (Paz-Bailey et al, 2013), such changes may lead to more transmission and more newly diagnosed patients presenting with advanced infection, despite the widespread availability of antiretroviral therapy (ART)
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