Pharmacodynamics of Antiretroviral Chemotherapy

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Abstract
Most clinicians are both familiar and comfortable with antibacterial chemotherapy. In large part, this is due to the relatively broad therapeutic-toxic window presented by most antibacterial agents, especially the beta-lactam class of drugs. Except for the occasional patient, little thought is given to overdosage, even (inappropriately) when organ function is impaired. Rather, the focus has been on providing demonstrably effective concentrations of drug as early in the course of the infection as possible. This has the rational aim of maximizing therapy from the very beginning, in order to minimize mortality and infectious morbidity. This is possible because of the paucity of drug-related morbidity in this setting.Antiretroviral therapy sometimes has been compared with oncologic chemotherapy, mostly because of the more toxic nature of antiviral agents. This is a mistake. The aim of oncologic chemotherapy is to reduce the number of malignant cells in the body to as close to zero as possible. This is best accomplished by the largest tolerable dose of oncolytic agent. These two linked ideas have driven virtually all of oncologic drug development. Indeed, the explicit aim of Phase 1 and Phase 2 trials in oncolytics is to identify the largest tolerable dose of drug. In contrast to anti-infective chemotherapy, the focus is almost exclusively on the relationship between drug exposure and the development of toxicities.