In 2002, Dr. Marconi’s initial research focused on laboratory models of HIV drug resistance followed by the development of clinical cohorts in South Africa. From these cohorts, seminal descriptions of antiretroviral adherence, resistance mutations, and clinical outcomes informed future implementation trials to improve clinical practice including palliative care and motivational interviewing (Living Well, STEP, and FIRST), commitment contracts (Incentive), digital health devices (Positive Health Check and TRAC), resistance testing (REVAMP), and the integration of noncommunicable diseases care into HIV clinics (iHEART-SA). After fellowship, he broadened his scope to explore the role of the immune system in host-pathogen interactions as they relate to clinical outcomes, aging, and mortality. He helped to develop additional local (Emory CFAR) and national (VA SHIELD) cohorts. His research team participates in ACTG, ACTT, NA-ACCORD, VACS, RECOVER, SUPERNOVA, the Martin Delaney Collaboratory, the U.S. Military HIV Natural History Study, and the Million Veterans Program. This work identified fundamental mechanisms of HIV infection in long-lived CD4+ T-cell subsets, natural control of HIV replication, and multi-omics pathogenesis studies, thereby elucidating the critical drivers of viral persistence, suboptimal CD4+ T-cell recovery, and age-related comorbidities after initiation of antiretroviral therapy. These studies inspired two clinical trials aimed to mitigate the impact of inflammation on health for people with HIV including the use of compassion-based meditation (CBCT) and exercise (FIT-VET). As an extension of his focus on the role of systemic inflammation in HIV disease, he explored the use of JAK-STAT inhibitors to reduce inflammation during both HIV and COVID-19, resulting in five national/international randomized-controlled trials, including three as protocol co-PI/chair (ACTG 5336, COV-BARRIER, and COV-BARRIER OS7). These studies directly impacted clinical care guidelines internationally.