HIV undergoes a continual process of evolution after primary infection, and it seems that the balance between evolutionary pressures on HIV and the success of the virus population in adapting to these pressures are the major determinants of the rate of disease progression. In the body as a whole, this ongoing struggle is reflected in the level of viral load and the CD4 cell count, but within the virus population this struggle is evident in changes in the genetic characteristics of viruses.

During primary infection, viruses which are adapted to gaining entry to cells displaying the CCR5 chemokine receptor are likely to predominate. However, viruses which can also gain access to cells by using the additional route of the CXCR4 chemokine receptor come to predominate over the CCR5 variants, and are associated with a much more rapid loss of CD4 T-cells. This is because HIV which is adapted to infecting cells which display the CXCR4 chemokine receptor will have a preference for infecting type 2 (Th2) CD4 T-cells. HIV replication in Th2 CD4 T-cells is much more rapid than in Th1 cells, which are preferentially infected by CCR5-tropic virus.

This switch towards a virus population which can infect more hospitable host cells is accompanied by other events, most notably the change from non-syncitium inducing (NSI) to syncitium-inducing (SI) virus. This means that viruses can begin to induce cell killing in uninfected CD4 T-cells.