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While at Penn State, Professor Piovoso began collaborating with Professor Zurakowski from the University of Delaware on system biology. In particular, Professor Piovoso, together with Dr. Zurakowski’s group, helped develop mathematical models for HIV and its interaction with drugs and obtained accurate estimates of model parameters and their likely distribution. Later, a study of HIV patients whose virus was under control and then administered an additional drug, raltegravir, became available. Raltegravir targets an HIV enzyme, integrase and prevents the integration of the viral genetic material into human chromosomes. Failure to integrate produces 2-‐LTR circles which were measured in the patients after administering the drug. This data of 2-‐LTR circles over time was model. The model’s behavior for approximately 1/3 of the patients, could only be explained by on-going viral replication. We hypothesized that this replication was occurring in lymph nodes. This conclusion is contrary to existing theory on the persistence of HIV virus. Models of how viral replication might be occurring in lymph nodes produced LTR circles consistent with measured results.
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JOURNAL OF THEORETICAL BIOLOGY (2023): 111651-111651
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