Thursday, June 06, 20192:00 PM - 3:00 PMCNLS Conference Room (TA-3, Bldg 1690)|
Investigating hypotheses regarding the development of drug resistance and the persistence of HIV in hosts through mechanistic modeling
Tremendous progress was made in treating people living with HIV. Nowadays, antiretroviral therapy usually allows patients to suppress viral loads for several years, if not decades. Despite this scientific achievement, chronic drug intake is usually necessary as no treatment can completely eradicate the virus. Further, the number of treatment options can become seriously limited over time if patients’ viruses develop and accumulate drug resistance. Questions remain concerning the source of these two issues (resistance and persistence of the virus). Inparticular, why are there so many cases of drug resistance when concentrations in blood are sufficiently inhibitive in vitro? Also, is it possible to detect poor drug penetration in tissues, a potential obstacle to the full eradication of the virus, from viral loaddecay curves? I will address these two issues through a quantitative systems pharmacology approach supported by clinical data. In particular, we developed models that bridge multiple scales, going from molecular, to viral, then cellular and finally to the clinical level. By assessing the ensuing models’ ability to explain and reproduce empirical data, we studied the consistency of hypotheses regarding the causality of studied phenomena.
Host: David Métivier