HIV is not cured with current therapeutic strategies. This is because of a large reservoir of cells with HIV proviral DNA that can reactivate and produce new virus. There is a significant gap in our understanding of the dynamic nature of this reservoir, how is it formed, what cellular and anatomic compartments are important, and how it is replenished. We will take advantage of a unique cohort of HIV infected people in Bangkok, Thailand to address these knowledge gaps. These individuals are identified as being HIV+ even before seroconversion because they are at high-risk for HIV infection and are screened frequently. When they are found to be HIV+ they are enrolled into a prospective study where lymphatic tissues are collected on a longitudinal basis. We will apply state of the art molecular and in situ technologies to these serial samples to define the precise size and location of the reservoir and the impact of very early treatment on reservoir size. For comparison we will study age and sex matched individuals started on treatment during chronic infection. The ability to study individuals at each Fiebig Stage of acute infection provides ?snapshots? of the reservoir as it is established and will give us insight into the dynamic nature of its formation, maintenance and replenishment. We hypothesize that viral reservoirs become established as early as Fiebig 1, that the cell type supporting the reservoir differs by anatomic location, and that ongoing, persistent immune activation is a significant factor in its replenishment. These data may point to new therapeutic targets to control or eradicate the latent reservoir which is a critical step in the path to a cure of HIV.
Impact Statement HIV is not curable with current treatments because there is a large reservoir of infected cells that antiretroviral therapy doesn't clear. This latent reservoir can occasionally reactivate to make infectious virus that can spread to other cells, thus replenishing the reservoir. We will study a unique cohort of patients with acute HIV infection to understand how this reservoir is formed and maintained. A better understanding of this process may lead to new interventions that can eradicate the virus reservoir and lead the way to a cure for HIV infection.
