Pharmacology lessons from chemoprophylaxis studies

Pharmacological studies in the context of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) are fundamental to inform on different drug pharmacokinetics, pharmacodynamics, and pharmacogenetics in view of the absence of easily measurable surrogate markers of efficacy. Although the combination of tenofovir and emtricitabine is the only PrEP agent that was studied and showed efficacy in preventing HIV transmission, prospective randomized clinical trials have reported varying efficacy due to poor adherence to the drug. Importantly, this could be overcome by the introduction of long-acting injectable PrEP agents, which may be administered monthly and ensure optimal and prolonged drug exposure in HIV target tissues. Notably, clinical pharmacology studies play a central role in interpreting drug concentration-responses and optimal drug exposure achievement.