People who delay antiretroviral therapy continue to be at higher risk for complications and death years later, apparently due to greater inflammation. The START trial randomly assigned newly diagnosed individuals to begin treatment either immediately or when their CD4 count fell below 350 or they developed AIDS symptoms. People who started immediately had a 57% lower risk of AIDS-related events, serious non-AIDS events or death. The randomized portion of the trial was halted in 2015, but follow-up continued. A START sub-study measured biomarkers of inflammation and blood coagulation. During the randomized study period, the delayed treatment group had higher levels of IL-6 and D-dimer. During 2016–2021, the delayed group had about a 30% higher risk of complications or death despite starting treatment. What’s more, participants with the highest IL-6 and D-dimer levels in both the immediate and delayed groups had about double the risk. These findings emphasize the importance of prompt diagnosis and early treatment.