Linkage disequilibrium test implies a large effective population number for HIV in vivo

The effective size of the HIV population in vivo, although critically important for the prediction of appearance of drug-resistant variants, is currently unknown. To address this issue, we have developed a simple virus population model, within which the relative importance of stochastic factors and purifying selection for genetic evolution differs over, at least, three broad intervals of the effective population size, with approximate boundaries given by the inverse selection coefficient and the inverse mutation rate per base per cycle. Random drift and selection dominate the smallest (stochastic) and largest (deterministic) population intervals, respectively. In the intermediate (selection-drift) interval, random drift controls weakly diverse populations, whereas strongly diverse populations are controlled by selection. To estimate the effective size of the HIV population in vivo, we tested 200 pro sequences isolated from 11 HIV-infected patients for the presence of a linkage disequilibrium effect which must exist only in small populations. This analysis demonstrated a steady-state virus population of 10(5) infected cells or more, which is either in or at the border of the deterministic regime with respect to evolution of separate bases.