Comparing the Frequencies of Contraindicated Drug-Drug Interactions Between Differing Antiretroviral Regimens in HIV-Infected Patients.

BACKGROUND: HIV-infected patients receiving antiretroviral therapy (ART) are at risk for contraindicated drug-drug interactions (XDDIs). OBJECTIVE: This study compared the frequency of XDDIs between different types of ART regimens. METHODS: A retrospective cohort study was performed among adult HIV-infected patients receiving care at either the Upstate New York Veterans' Healthcare Administration or the University of New Mexico Truman Health Services between 2000 and 2013. The cohort consisted of patients receiving traditional ART regimens composed of 2 nucleoside reverse transcriptase inhibitors plus either a nonnucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase strand transfer inhibitor (INSTI). The primary outcome was the presence of XDDIs. Lexi-Interact was used to define XDDIs. RESULTS: Of the 1329 patients who met inclusion criteria, 45.7%, 34.2%, and 20.1% were receiving an NNRTI-, PI-, or INSTI- based ART regimen, respectively. Among the 128 (9.6%) patients with an XDDI, more than half (53.9%) had an interaction involving ART. The presence of XDDIs was highest for PI-based regimens (16.3%) compared with INSTI- (7.9%) and NNRTI-based (5.4%) regimens; P < 0.001. The variables independently associated with XDDIs were ART regimen type (prevalence ratio [PR] = 1.91; 95% CI = 1.51-2.40, P < 0.001), use of ≥6 non-HIV medications (PR = 5.84; 95% CI = 3.92-8.71, P < 0.001), and age ≥40 years (PR = 1.62; 95% CI = 0.92-2.86, P = 0.10). CONCLUSION: The probability of XDDIs varies as a function of ART regimen type, advanced age, and use of multiple non-HIV medications.

Prevalence and Predictors of Important Telaprevir Drug Interactions Among Patients Coinfected With Hepatitis C and Human Immunodeficiency Virus.

Background: Among patients with HIV and hepatitis C (HCV) coinfection, drug-drug interactions involving nonstructural protein 3/4 (NS3/4A) serine protease inhibitors for HCV infection are an important concern because these drugs affect cytochrome P450 metabolism and p-glycoprotein transporters. Objectives: The primary objective was to determine the prevalence of clinically significant drug-drug interactions (CSDDIs) in HIV/HCV coinfected patients if telaprevir-based HCV therapy is added to patients' medication regimens. Secondary objectives were to identify antiretroviral therapy (ART) regimens associated with the lowest risk of CSDDI and determine the clinical risk factors. Methods: A cross-sectional study was performed among adult HIV/HCV coinfected patients. Demographics, comorbidities, social history, and medication lists were extracted from medical records. For each patient, CSDDIs were identified by entering all medications and pegylated interferon, ribavirin, and telaprevir into Lexi-Interact drug interaction software. The number and nature of CSDDIs were recorded before and after addition of telaprevir-based therapy. Results: There were 335 patients included. Prior to the addition of telaprevir-based HCV therapy, there was a high frequency (82.1%) of any CSDDI. After the addition of telaprevir-based HCV therapy, the frequency of any CSDDI increased to 97% (P < .001). Contraindicated interactions rose from 20.0% to 38.2% of patients after addition of telaprevir-based therapy. Use of ≥10 non-HIV medications, dyslipidemia, and HIV protease inhibitors were independently associated with the occurrence of a contraindicated interaction. Conclusions: Clinicians considering initiating telaprevir in HIV/HCV coinfected patients should be vigilant of drug-drug interactions, particularly among patients with dyslipidemia, those using ≥10 non-HIV medications, and those using HIV protease inhibitors.

Short Communication: Relationship Between Contraindicated Drug-Drug Interactions and Subsequent Hospitalizations Among Patients Living with HIV Initiating Combination Antiretroviral Therapy.

Persons living with HIV (PLWH) are at an increased risk of contraindicated drug-drug interactions (XDDIs), which may result in deleterious outcomes. Study objectives were to (1) compare the frequency of hospitalizations between patients with and without XDDIs and (2) determine if XDDIs are independently associated with hospitalizations in PLWH. A retrospective cohort study was performed among PLWH receiving care at the Upstate New York Veterans' Healthcare Administration or University of New Mexico Truman Health Services from 2000 to 2013. Hospitalization was defined as an admission to an inpatient hospital facility for ≥24 h. Of the 1329 patients evaluated, 149 (11.2%) patients were hospitalized within 1 year of antiretroviral therapy initiation. A significantly higher proportion of patients with XDDIs were hospitalized compared with those who did not have XDDIs (20.3% vs. 10.2%, risk ratio: 1.98, 95% confidence interval [CI]: 1.35-2.91, p = .001). In the multivariate Cox proportional hazards regression analyses, XDDIs were independently associated with hospitalizations (hazard ratio [HR]: 1.58; 95% CI: 1.00-2.48; p = .05), after adjustment for CD4 < 242 cells/mm3 (HR: 2.38; 95% CI: 1.72-3.33; p < .001), protease inhibitor (PI)-based regimen (HR: 1.35; 95% CI: 0.97-1.89; p = .08), recreational drug use (HR: 2.58, 95% CI: 1.85-3.58, p < .001), and non-HIV medications ≥10 (HR: 1.62; 95% CI: 0.97-2.69; p = .07). In this study an increased risk of hospitalization was observed among PLWH with XDDIs compared with those without XDDIs. This relationship persisted after adjustment for CD4 count, use of a PI-based regimen, recreational drug use, and number of non-HIV medications.

A Cross-Sectional Study Comparing the Frequency of Drug Interactions After Adding Simeprevir- or Sofosbuvir-Containing Therapy to Medication Profiles of Hepatitis C Monoinfected Patients.

INTRODUCTION: This study compares the expected occurrence of contraindicated drug-drug interactions (XDDIs) when simeprevir (SIM)- or sofosbuvir (SOF)-containing therapy is added to medication profiles of patients with hepatitis C (HCV) monoinfection to quantify, in relative terms, the population-based risk of XDDIs. Second, this study identified the predictors of XDDIs when HCV therapies are added to medication profiles. METHODS: A cross-sectional study was performed among Veterans' Affairs patients. Inclusion criteria were: (1) age ≥18 years, (2) HCV infection, and (3) availability of a medication list. Patients with human immunodeficiency virus were excluded. Demographics, comorbidities, year of HCV diagnosis, and most recent medication list were collected from medical records. The primary outcome was the presence of XDDIs involving HCV therapy and the medications in the patient's home medication list after the addition of either SIM- or SOF-containing regimens. To define XDDIs, Lexi-Interact drug interaction software was used. RESULTS: 4,251 patients were included. The prevalence of XDDIs involving SIM- or SOF-containing therapy were 12.6% and 4.7% (p < 0.001), respectively. In multivariable analyses examining the predictors of XDDIs involving SIM-containing therapy, the only medication-related predictor was use of ≥6 home medications (odds ratio OR 4.58, 95% confidence interval CI 3.54-5.20, p < 0.001). Similarly, use of ≥6 home medications was also the only variable associated with an increased probability of XDDI involving SOF-containing therapy (OR 3.83, 95% CI 2.57-5.70, p < 0.001). CONCLUSIONS: Sofosbuvir-containing therapy had a lower frequency of XDDIs than SIM-containing therapy. Polypharmacy with various classes of home medications predicted XDDIs involving SIM- or SOF-containing therapy.

Prevalence of drug-drug interactions upon addition of simeprevir- or sofosbuvir-containing treatment to medication profiles of patients with HIV and hepatitis C coinfection.

The objectives were to (1) compare the frequency of contraindicated drug-drug interactions (XDDI) when simeprevir (SIM)- and sofosbuvir (SOF)-containing regimens are theoretically added to a patient's medication profile; (2) identify which hepatitis C (HCV) regimen is associated with the lowest frequency of XDDIs within different types of antiretroviral treatment (ART) regimens; and (3) determine the risk factors for XDDIs with each regimen. A cross-sectional study was performed among adult HIV/HCV-coinfected patients. Demographics, comorbidities, and medication lists were collected from medical records. Medication lists were entered into Lexi-Interact drug interaction software and XDDI before/after the addition of SIM- and SOF-containing therapy was documented. Classification and regression tree (CART) analyses identified breakpoints in continuous variables. Before the addition of any HCV therapy, XDDIs were present in 20% of the 335 included patients. After the addition of SIM-containing therapy, the frequency of XDDIs significantly increased to 88.4% (p<0.001). After adding SOF-containing therapy, the prevalence of XDDIs increased to 24.5% (p<0.001). The prevalence of XDDIs was significantly lower for SOF-containing HCV therapy within various types of ART regimens. Use of ≥7 non-HIV medications (CART breakpoint) was the only variable to predict XDDIs before the addition of any HCV therapy. Similarly, this was the only variable to predict XDDIs after the addition of SOF-containing therapy (PR: 4.80; 95% CI: 2.57-8.96, p<0.001). Variables independently associated with XDDIs after the addition of SIM-containing therapy were NNRTI regimen (prevalence ratio, PR: 1.62; 95% confidence interval, CI: 1.38-1.91, p<0.001), PI regimen (PR: 1.64; 95% CI: 1.40-1.93, p<0.001), and ≥7 non-HIV medications (PR: 1.06; 95% CI: 1.00-1.14, p=0.09). The addition of SOF-containing therapy was associated with a lower prevalence of XDDI than SIM-containing therapy.