Phylogenetic inference for the study of within-host HIV-1 dynamics and persistence on antiretroviral therapy

Although antiretroviral therapy (ART) is highly effective at inhibiting HIV-1 replication and preventing AIDS, it cannot eradicate the infection. Many studies have used viral genetic information from single-genome and deep sequencing of blood and tissue samples to investigate the mechanisms that sustain the HIV-1 reservoir. Sequence data are analysed by use of measurements of population diversity and divergence and by exploration of phylogenetic associations. The study of intrahost HIV-1 populations on ART requires specific considerations as their dynamics can be shaped by host factors such as cell death and proliferation. Hence, understanding both the biology of HIV-1 persistence and the phylogenetic methods that can be applied to this field is crucial. We conclude that the most suitable phylogenetic methods and evolutionary models for characterising HIV-1 populations on ART include using neighbour-joining trees to identify identical proviral sequences that might result from T-cell proliferation, and using maximum-likelihood analysis to investigate the possibility of ongoing viral replication on ART. Characterising the reservoir for HIV-1 on ART is a high priority for the design of curative interventions.