Pharmacogenomics and Implications for Nursing Practice.

PURPOSE: This article aims to introduce the nurse to pharmacogenomics and its implications for clinical practice with regard to drug therapy. ORGANIZING CONSTRUCTS: Pharmacogenomics is discussed with regard to the basic tenets, relationships to common health conditions, education and practice resources, and implications for nursing practice. METHODS: Peer-reviewed literature, websites, and expert professional guidelines were reviewed with relation to pharmacogenomics and nursing practice. FINDINGS: The genetic-genomic literature has grown significantly since the completion of the Human Genome Project in 2003. This information is now being translated into practice with regard to the patient's genetic profile and the impact on drug therapy, which is pharmacogenomics. CONCLUSIONS: The utilization of the patient genetic-genomic profile is beginning to have an impact on patient drug therapy in clinical practice. CLINICAL RELEVANCE: Nurses are in the position to make sure, with the increased translation of pharmacogenomics into clinical practice, that adverse drug reactions are avoided and doses are optimized.

Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir.

Substance use is highly prevalent in HIV-infected individuals in the United States, and clinical management is complicated by the need for antiretroviral treatment, addiction therapy, variable medication adherence, and co-morbidities. The interrelation between HIV and substance use prompted our investigation to examine substance use and self-reported medication adherence in patients receiving the HIV-1 protease inhibitors, atazanavir (ATV) or lopinavir (LPV). ATV and LPV pharmacokinetics were determined by measuring plasma concentrations in subjects with active substance use (SU group) or with no active substance use (NSU group). No difference in adherence was observed between groups (p > 0.05). The mean SU ATV trough was 0.550+/-0.45 microg/mL; the mean NSU ATV trough was 0.780+/-0.590 microg/mL (p > 0.05). The mean SU LPV trough was 4.02+/-2.39 microg/mL; the mean NSU LPV trough was 6.67+/-0.910 microg/mL (p = 0.01). Co-factors found to be associated with variation in ATV and LPV concentrations included concurrent methadone use, cigarette smoking, and substance use status. These data indicate that chronic HIV treatment may be assisted with plasma concentration monitoring to identify those patients who may require dosage modification and/or regimen adjustment in order to optimize antiretroviral effects.

Advances in pharmacogenomics of antiretrovirals: an update.

Recent developments in the pharmacogenomics of antiretroviral drugs provide new prospects for predicting the efficacy of treatment and potential adverse effects. HIV/AIDS is a serious but treatable infectious disease, yet current treatment is limited by high rates of adverse drug reactions and development of resistance due to suboptimal drug concentrations in a significant proportion of patients. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be quantified and certain adverse effects can be assessed with validated measures. Additionally, there is increasing knowledge of the pharmacokinetics and dynamics of antiretroviral drugs, and some candidate genes implicated in the metabolism, transport and adverse effects have been identified. However, recent studies of the association of particular genes and their genetic variants with HIV management and adverse drug reactions have not provided unifying conclusions. This article reviews the most recently published work and summarizes the state of research in this area. Future directions for research and the application of this technology to the clinical practice of individualizing treatment for HIV management are discussed.

Assessing the impact of substance use and hepatitis coinfection on atazanavir and lopinavir trough concentrations in HIV-infected patients during therapeutic drug monitoring.

Atazanavir (ATV) and lopinavir (LPV) are widely used HIV-1 protease inhibitors. Like with other protease inhibitors, careful monitoring of potential drug-drug and drug-disease interactions in clinical practice is necessary. The aim of this study was to assess the impact of substance use and hepatitis virus coinfection on plasma ATV and LPV trough concentrations in HIV-positive substance users and nonusers. Individuals established on ATV (300 mg and 100 mg ritonavir daily) or LPV (400 mg and 100 mg ritonavir twice daily)-containing regimens completed two clinical visits (trough and directly observed therapy) during which dosing characteristics, concomitant medication, and substance use were recorded. Trough plasma concentrations (22-26 hours for ATV and 10-14 hours for LPV) were measured using LCMSMS. The influence of substance use was evaluated by Kruskal-Wallis test. Substance use was associated with a marked decrease in trough LPV concentrations during the trough visit (median, 5.536 and 3.791 microg/mL for nonsubstance users and substance users, respectively, P = 0.029). Significantly lower LPV trough levels were also noted among patients with active hepatitis C virus coinfection evaluated as an independent variable (median, 2.253 and 5.927 microg/mL for active and inactive/no hepatitis C virus infection, respectively, P = 0.032). Substance use and hepatitis virus coinfection had limited effects on ATV trough levels. In this cohort, despite the wide interindividual variability of ATV and LPV trough concentrations, significant associations between substance use and active hepatitis C virus infection and low LPV trough concentrations were observed. Further work is needed to assess the optimal dosing regimen when using LPV in HIV-infected substance users.