Phylogenetics and molecular evolution to understand and curb the HIV pandemic.

Despite decades of research and medical advances, the HIV-1 pandemic still presents major public health challenges, with most countries failing to meet the defined targets for HIV elimination. HIV-1 is the first chronic viral disease for which extensive virus sequence data became available through genotypic resistance testing. Phylogenetic methods have been instrumental in answering pathogenesis-related questions, such as ongoing viral replication on antiretroviral therapy and the role of the viral genome in pathogenesis and immunity. Molecular data have also largely enabled the development and application of phylogenetic and molecular epidemiology approaches to large populations, providing unique insights. These insights include the origin and timing of the HIV-1 pandemic, its global spread, transmission dynamics within and between subpopulations, and quantifying the impact of public health interventions on ongoing transmission. Such knowledge is essential for improving our understanding of key epidemic dynamics at both the micro and macro levels, as well as of the underlying biological mechanisms. In the future, these insights could be provided in real time to guide and optimize prevention measures. Molecular public health approaches should be expanded, particularly in low-income and middle-income countries where most of the pandemic's burden persists.