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Over the past decade, there have been numerous advances in HIV therapy, with 6 drug classes comprising 24 indivi dual antiretroviral agents now available. For patients who are adherent with therapy and who have an undetectable viral load, HIV has become a chronic, manageable disease in an aging and genetically diverse population. The core goals of management remain maximal suppression of viral replication and promotion of immune reconstitution through combination antiretroviral therapy. Secondary goals of therapy include promoting long-term adherence, avoiding drug interactions, minimizing toxic effects, simplifying treatment regimens, decreasing drug costs, managing comorbid conditions, and preventing transmission of HIV by achieving undetectable viral load. Consequently, the pharmacist’s role has evolved and expanded to help patients and other health care providers to achieve these goals. Pharmacists are recognized as established and integral members of HIV health care teams across Canada and the United States. Pharmacists’ involvement in the care of HIVpositive patients has been associated with improved patient outcomes, including enhanced adherence, reduced pill burden and dosing frequency, greater increases in CD4 cell counts, higher rates of viral suppression, and decreases in medication errors. Guidelines and position statements on the role of the pharmacist in caring for patients with HIV/AIDS have been published by various national and international organizations, but there have been no updates since combination antiretro viral therapy came into use, about a dozen years ago. This paper provides current guidelines for a pharmacist’s role in the many aspects of caring for patients with HIV/AIDS, including selecting and reviewing therapy, tailoring treatment for specific populations, counselling patients, monitoring response to therapy, guiding transitions of care, and undertaking scholarly and professional activities. The target audience for these guidelines includes new HIV pharmacy practitioners, pharmacists with an interest in HIV but limited experience or therapeutic knowledge in this area, and pharmacy students. This paper may also serve as a model of pharmacy practice for ambulatory care in other therapeutic areas. A literature search was conducted using the electronic databases MEDLINE and PubMed from 2000 to March 2012. The following search terms were used: HIV, antiretrovirals, adverse drug reactions, drug interactions, adherence, pediatric, perinatal transmission, therapeutic drug monitoring, pharmacist, hepatitis B, hepatitis C, seamless care, and medication reconciliation. In addition, conference abstracts were searched for relevant studies. Updated guidelines for treatment of HIV and related conditions, landmark studies, and comprehensive review articles were selected for inclusion.

Therapeutic drug monitoring (TDM) is a strategy whereby the plasma concentration of one or more drugs is measured and drug doses are adjusted accordingly to achieve concentrations within an acceptable therapeutic range. The goal of TDM is to maximize pharmacologic efficacy and minimize the drug’s toxic effects, and hence to contribute to optimizing the patient’s outcomes. In general, TDM is indicated if the following conditions are present: there is a direct relationship between drug exposure and pharmacologic response, the drug has a narrow therapeutic index and is used to treat a condition for which drug failure or toxicity is associated with substantial morbidity or mortality, and there is limited intrapatient but wide interpatient pharmaco kinetic variation. Differences in pharmacokinetic factors among patients are multifactorial and may include age, sex, ethnic background, pregnancy, and body weight, as well as comorbid conditions causing variations in hepatic function, renal function, drug absorption, and drug disposition. In some cases, genetic polymorphisms in the cytochrome P450 enzymes may explain the large interpatient variability for certain antiretroviral agents. For example, certain CYP2B6 and CYP2A6 polymorphisms are independent predictors of plasma concentrations of efavirenz. Moreover, the potential for complex or unpredictable drug–drug or drug–food interactions can significantly affect plasma drug concentrations. Finally, TDM depends on the availability of an accurate and feasible analytical method for a given drug. Among antiretroviral agents, the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) are considered suitable candidates for TDM. Evidence exists of a relation between exposure to antiretrovirals and virologic response and, in more limited instances, between exposure to the drug and toxic effects. Recent data have suggested that intraindividual variation is limited (19.0% for NNRTIs and 38.1% for protease inhibitors). Preliminary data have also suggested that trough levels of maraviroc, a chemokine (C–C motif) receptor 5 (CCR5) antagonist, are predictive of virologic outcome, although TDM experience with this agent is extremely limited. In retrospective and prospective studies, observed interindividual variability in drug concentrations has been 45% to 112% for protease inhibitors and 75% for NNRTIs. Thus, a given dose of a particular antiretroviral agent may result in unacceptable toxic effects in some patients while yielding subtherapeutic concentrations in others. TDM represents a tool by which the effectiveness of these agents in clinical practice can be optimized through dosage adjustments tailored to patient-specific pharmacokinetic and pharmaco dynamic parameters. The current article reviews the literature on antiretroviral TDM, describes the development of an antiretroviral TDM program in Canada, and illustrates the role of the pharmacist in the clinical application of TDM. Given current evidence and personal experience, the authors support the use of antiretro viral TDM as a clinical tool in special patient populations and for specific clinical situations.