The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

The introduction of Highly Active Antiretroviral Therapy (HAART) as standard of care has changed the natural history of HIV infection into a manageable chronic disease requiring long-term Antiretroviral (ARV) Treatment. However, despite of the long-time experience and the vast drug armamentarium available for HIV infection, variability in efficacy and toxicity remains as an important limitation for managing HIV infection. There are multiple factors affecting the variability of ARV response, including ethnicity, gender, age, body weight, drugdrug and drug-food interactions, binding to plasma proteins, hepatic impairment, disease status, pregnancy, and host genetic factors. Genetic variations in pathways of drug absorption, disposition, metabolism and excretion (ADME) may explain the interpatient variability and therefore, genes encoding for transport proteins, drug-metabolizing enzymes or nuclear receptors that encode for both transporters and enzymes, have been the main targets of HIV pharmacogenetic studies so far (Figure 1).