Prevalence and risk factors for clinically significant drug interactions with antiretroviral therapy

Christopher D Miller, Ramy El-Kholi, John J Faragon, Thomas P Lodise
Pharmacotherapy 2007, 27 (10): 1379-86

STUDY OBJECTIVES: To identify the prevalence and types of clinically significant drug interactions (CSDIs) in the drug regimens of patients with human immunodeficiency virus (HIV) infection who were receiving antiretroviral therapy, and to explore risk factors for these CSDIs.

DESIGN: Retrospective medical record review.

SETTING: Academic HIV specialty clinic.

PATIENTS: One hundred fifty-three randomly selected patients with HIV infection who were receiving antiretroviral therapy from May 1-September 30, 2006.

MEASUREMENTS AND MAIN RESULTS: Data were collected on patient demographics, date of HIV diagnosis, most recent viral load and CD4(+) count, Centers for Disease Control and Prevention HIV classification, and comorbid conditions. Patients' drug regimens were analyzed for total and clinically significant antiretroviral drug interactions using three resources. Logistic regression and classification and regression tree analysis were used to identify independent CSDI predictors. Clinically significant drug interactions were defined as drug interactions that required a dosage adjustment or consisted of a drug combination that is contraindicated due to its high potential for clinical adverse effects. Of the 153 patients, at least one CSDI was found in 41.2% of their regimens: 34.6% with at least one drug interaction that required a dosage adjustment, 2.0% with at least one contraindicated drug combination, and 4.6% with at least one of each of these CSDIs. In the logistic regression model, risk factors independently associated with CSDIs were age older than 42 years (odds ratio [OR] 2.9, 95% CI 1.2-7.1), more than three comorbid conditions (OR 3.0, 95% CI 1.4-6.6), treatment with more than three antiretroviral agents (OR 2.4, 95% CI 1.0-5.8), and treatment with a protease inhibitor (OR 11.5, 95% CI 4.2-31.2). When directly compared, CSDIs were more prevalent among protease inhibitor-based than nonnucleoside reverse transcriptase inhibitor-based regimens (p<0.001).

CONCLUSION: Clinically significant drug interactions are highly prevalent among HIV-infected patients receiving antiretroviral therapy. Knowledge of the risk factors for CSDIs may help clinicians recognize and manage CSDIs.

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