iKnow is an NIH-funded study that aims to advance understanding of the reasons people living with HIV lose, gain or sustain viral suppression in key groups and inform the development and targeting of interventions to minimize time spent without viral suppression. The study will enroll a diverse cohort of 2,000 people (1,500 MSM and 500 transfeminine people) living with HIV infection in the US through virtual recruitment and follow each participant using limited interaction methods for 24 months; collect data on care engagement and viral load, multilevel predictors of care engagement and viral suppression, experiences of stigma in and outside of healthcare settings, care seeking behaviors, substance use, and sexual practices; use purposive qualitative interviewing and multilevel modeling to understand the factors associated with gaining or losing viral suppression and how those factors differ for key subgroups of PLWH; and, in collaboration with the CDC, use mailed self-collected blood specimens to assess acceptability and feasibility of remote monitoring of HIV viral load as well as the potential impact of more frequent HIV viral load monitoring on reducing HIV transmission.