Hiv And Its Effects On Acute Infection - 2385 Words

HIV-1 establishes a reservoir in lymphoid tissue during acute infection that is the site of virus production from infected cells, storage in immune complexes on the surface of the follicular dendritic cell (FDC) network, and persistence in a pool of latently infected resting memory CD4+ T cells 1-8. While combinations of antiretroviral drugs can suppress viral replication and reduce viral RNA to undetectable levels in plasma, virus production from this reservoir of latently infected cells rekindles HIV-1 infection if drug treatment is stopped 9. The elimination or inactivation of latently infected cells in reservoirs that give the virus safe haven from antiretroviral drugs or immune attack is key to bring about a cure. Intermittent virus†¦show more content†¦Under these conditions, virus might continue to evolve in a small sanctuary site within the reservoir of cells in lymph nodes and remain undetectable in blood depending on as yet unknown trafficking relationships between the two compartments. Here, we tracked the evolution of HIV-1 and inferred the dispersal patterns among discrete anatomic compartments in time-resolved phylogenies. With a model of within-host infection dynamics, which encodes drug-dependent viral fitness and site-dependent evolutionary pressures, we show that, in patients with undetectable levels of virus in their blood, low amounts of viral replication can occur in a sanctuary site with suboptimal drug concentrations that do not breed drug-resistant strains. We applied massively parallel sequencing to HIV-1 provirus populations in cells from blood and lymph nodes collected at three separate times (day 0, and after 3 months and 6 months of treatment) and virus particles in the blood (day 0) from three study subjects studied previously (Fig. 1; 12). Two subjects (1727 and 1679) were well-suppressed patients; and the third subject (1774) continued to have measureable amounts of viral RNA in plasma after 3 months, but not 6 months of treatment. Subjects 1727 and 1679 were each infected with HIV-1 for approximately 3 to 4 months and were antiretroviral drug naà ¯ve. Subject 1774 was infected with HIV-1 for approximately 17 years and was antiretroviral drug