Predictors of Clinically Significant Drug-Drug Interactions Among Patients Treated with Nonnucleoside Reverse Transcriptase Inhibitor–, Protease Inhibitor–, and Raltegravir-Based Antiretroviral Regimens

Abstract

Background: The Department of Health and Human Services (DHHS) HIV treatment guidelines recommend that antiretroviral regimens for treatment-naïve individuals include at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus either (1) a nonnucleoside reverse transcriptase inhibitor (NNRTI), (2) a protease inhibitor (PI), or (3) raltegravir, an integrase strand transfer inhibitor. Differences in drug-drug interaction potential may represent an important differentiating feature when choosing between these regimen types. Objective: To identify risk factors for clinically significant drug-drug interactions (CSDDIs) among patients on NNRTI-, PI-, and raltegravir-based antiretroviral regimens; compare CSDDI risks between these regimen types; and develop a clinical prediction tool for antiretroviral CSDDIs Methods: In this cross-sectional study, outpatient medical records from the HIV clinic at Albany Medical Center Hospital were randomly selected to review patients’ current antiretroviral regimens. Patients treated with NNRTI-, PI-, or raltegravir-based regimens were included. Drug therapies were analyzed for interactions using Lexi-Comp drug interaction software. The CSDDIs were defined as either (1) a drug combination that is contraindicated or accompanied by strong precautions per DHHS antiretroviral guidelines or (2) a drug combination that necessitates a medication dose adjustment. Results: Of the 500 patient records screened. 229 were included. Baseline characteristics were similar between regimen groups, with the exception of comorbidities. In multivariate analyses, variables independently associated with CSDDIs were use of >5 non-antiretroviral medications (prevalence ratio [PR] 1.86; 95% CI 1.31 to 2.64: p< 0.001) and regimen type (NNRTI: PR 2.48, PI: PR 4.96, and rallegravir [referent]: PR 1.00; 95% CI 1.79 to 3.44; p < 0.001). Conclusions: Use of >5 non-antiretroviral medications or a non-raltegravir-based antiretroviral regimen increased the risk of a CSDDI. Our findings help clarify drug interaction risks among NNRTI-. PI-, and raltegravir-based regimen types that should be considered when prescribing antiretroviral therapy.