Understanding the dynamics of naive and memory CD4+ T cells in the immune response to HIV-1 infection can help elucidate typical disease progression patterns observed in HIV-1 patients. Although infection markers such as CD4+ T-cell count and viral load are monitored in patient blood, the lymphatic tissues (LT) have been shown to be an important viral reservoir. Here, we introduce the first comprehensive theoretical model of disease progression based on T-cell subsets and virus circulating between the two compartments of LT and blood. We use this model to predict several trademarks observed in adult HIV-1 disease progression such as the establishment of a setpoint in the asymptomatic stage. Our model predicts that both host and viral elements play a role in determining different disease progression patterns. Viral factors include viral infectivity and production rates, whereas host factors include elements of specific immunity. We also predict the effect of highly active antiretroviral therapy and treatment cessation on cellular and viral dynamics in both blood and LT.
Address correspondence and reprint requests to Denise Kirschner, Department of Microbiology and Immunology. 6730 Medical Science Building II. The University of Michigan Medical School, Ann Arbor. MI 48109-0620 U.S.A; e-mail:firstname.lastname@example.org
Manuscript received July 24, 2001: accepted January 23, 2002.
© 2002 Lippincott Williams & Wilkins, Inc.