An important recent development in the field of HIV/AIDS care and treatment is the discovery that taking an antiretroviral medication 2–24 h before high risk sexual activity followed by daily doses for 2 days significantly lowers risk for HIV transmission (1). This strategy, called preexposure prophylaxis or PrEP,3 is naturally changing behavior amongst high-risk groups who are HIV negative. The particular approach of taking pills just before and after a high-risk encounter is known as “on demand” or “intermittent” use and has important practical implications. The conventional dictate for antiretroviral therapy has been that maximal viral suppression occurs when patients take at least 90% of their doses. For PrEP, although the recommendation is still that largest protection is upon daily dosing, high-risk individuals may take the medication around only high-risk encounters. To understand how we can know when PrEP users have adequate protection to guide clinical, or in this case, preclinical care, we spoke with Dr. Peter Anderson, professor of pharmaceutical sciences at the University of Colorado, who has had a long interest in nucleoside analogs and has developed an assay to measure adherence to PrEP. To determine if an HIV positive patient is taking …