Relational concurrency, stages of infection, and the evolution of HIV set point viral load.

HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that populationmean SPVL (MSPVL) has evolved near an optimumthat reflects a trade-off between transmissibility and host survival. Sexual network structures affect rates of potential exposure during different within-host phases of infectionmarked by different transmission probabilities, and thus affect the number and timing of transmission events. These structures include relational concurrency, which has been argued to explain key differences in HIV burden across populations.We hypothesize that concurrency will alter the fitness landscape for SPVL in ways that differ from other network features whose impacts accrue at other times during infection. To quantitatively test this hypothesis, we developed a dynamic, stochastic, data-driven networkmodel of HIV transmission, and evolution to assess the impact of key sexual network phenomena onMSPVL evolution. Experiments were repeated in sensitivity runs thatmade different assumptions about transmissibility during acute infection, SPVL heritability, and the functional formof the relationship between VL and transmissibility. For ourmain transmission model, scenarios yielded MSPVLs ranging from4.4 to 4.75 log10 copies/ml, coveringmuch of the observed empirical range. MSPVL evolved to be higher in populations with high concurrency and shorter relational durations, with values varying over a clinically significant range. In linear regression analyses on these and other predictors,main effects were significant (P < 0.05), as were interaction terms, indicating that effects are interdependent. We also noted a strong correlation between two key emergent propertiesmeasured at the end of the simulations--MSPVL and HIV prevalence--most clearly for phenomena that affect transmission networks early in infection. Controlling for prevalence, high concurrency yielded higherMSPVL than other network phenomena. Interestingly, we observed lower prevalence in runs in which SPVL heritability was zero, indicating the potential for viral evolution to exacerbate disease burden over time. Future efforts to understand empirical variation in MSPVL should consider local HIV burden and basic sexual behavioral and network structure. [ABSTRACT FROM AUTHOR]