Background: The ability of the human immunodeficiency virus type 1 (HIV-1) to persist in anatomic compartments and cellular reservoirs is a major obstacle for eradication of replicationcompetent virus in the infected host.
Approach: We extensively review recent advancements in phylogenetic and phylogeographic techniques that provide a unique opportunity for studies of intra-host HIV-1 compartmentalization and the detection of potential reservoirs.
Conclusion: We show that infected macrophages in the central nervous system (CNS) harbor viral subpopulations that play a key role in the emergence of escape variants and viral rebound following discontinuation of antiretroviral therapy. An HIV cure, therefore, cannot be achieved without the effective targeting of the virus in the CNS, for which in depth knowledge of viral population dynamics contributing to the development and maintenance of latent reservoirs is critical.