OBJECTIVE: Compare the initial phases of virologic decay when acute/early and advanced HIV-infected adults are administered the same treatment regimen. DESIGN: Mathematical modeling of a previously completed prospective treatment pilot study involving treatment-naive patients with early and advanced immunosuppression. METHODS: We analyzed data from a treatment protocol in which 18 individuals with acute or recent HIV-1 seroconversion and six patients with advanced AIDS were administered the same four-drug antiretroviral regimen. Initial treatment responses were compared by fitting a mathematical model to frequent viral load measurements in order to calculate the first and second phase kinetics of viral clearance, and also by comparing viral load suppression over 24 weeks. Patients were also comprehensively compared in terms of protease inhibitor drug levels, HIV-specific immune responses at baseline, and the presence of drug resistance-conferring mutations. RESULTS: There was no statistically meaningful difference in first phase clearance of comparable high-level viremia in the two groups, whether protease inhibitor levels were inserted into the model or 100% antiviral drug effectiveness was assumed. In contrast, acute/early patients had inferior sustained responses than advanced patients, reflecting erratic adherence. CONCLUSIONS: Despite many years of intervening immune destruction, the initial virologic decay on therapy appears to be the same at the extremes of the HIV disease spectrum. © 2008 Lippincott Williams & Wilkins, Inc.