Stochastic or deterministic: what is the effective population size of HIV-1?

Various studies have attempted to estimate the effective population size of HIV-1 to determine the strength of stochastic effects in within-host evolution. The largely discrepant estimates, the complexity of the concept of the effective population size and the resulting uncertainty about the underlying assumptions make the interpretation of these estimates difficult. Here, we explain the concept and critically assess the current estimates. We discuss the biologically relevant factors that affect the estimate and use of the effective population size. We argue that these factors lead to an underestimation of the effective population size and, thus, to an overestimation of the strength of stochastic effects in HIV-1 evolution.