title: Protease inhibitor-associated QT interval prolongation.
abstract: OBJECTIVE
  To evaluate the literature on protease inhibitor (PI)-associated QT interval prolongation and risk for torsade de pointes in patients infected by HIV.
  
  
  METHODS
  Primary literature was identified through MEDLINE (1950-August 2011) and EMBASE (1980-August 2011), using the following search terms: antiretroviral agents, HIV, protease inhibitors, QTc, QT prolongation, and torsade de pointes.
  
  
  METHODS
  English-language case reports of antiretroviral therapy-associated QT interval prolongation, studies of healthy volunteers, or studies that evaluated the impact of PIs on QT interval in patients infected with HIV were reviewed and selected. Article bibliographies and conference abstracts were also reviewed.
  
  
  RESULTS
  Several case reports, as well as in vitro data, have implicated PIs as a potential cause of QT interval prolongation and/or torsade de pointes. Saquinavir, therapeutically boosted with the potent CYP3A4 inhibitor ritonavir, was the only PI shown to be associated with significant QT interval prolongation in studies with healthy volunteers. While 1 case control study in HIV-infected patients found that nelfinavir or efavirenz, a nonnucleoside reverse transcriptase inhibitor, increased the risk of QT interval prolongation, larger prospective studies have not demonstrated any significant increase in QT interval following exposure to PIs. Similar risk factors for QT interval prolongation seen in non-HIV-infected patients, such as older age, female sex, ethnicity, cardiac conditions, diabetes mellitus, and concomitant use of other QT interval-prolonging medications, especially methadone, were risk factors identified in studies of HIV-infected patients.
  
  
  CONCLUSIONS
  PIs do not appear to independently predispose patients to QT interval prolongation. However, other risk factors (both HIV-related and non-HIV-related) may increase the risk of QT interval prolongation. Available data suggest that baseline and follow-up electrocardiogram monitoring are unnecessary precautions, but may be considered in patients who are initiating PI therapy and are on multiple medications with proarrhythmic potential and/or have multiple comorbidities, increasing the risk.
authors: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors: Kimberley
authors: K
authors: Hunt
authors: Christine A
authors: CA
authors: Hughes
authors: Cara
authors: C
authors: Hills-Nieminen
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D016017:Odds Ratio; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D012307:Risk Factors; D016171:Torsades de Pointes / Q000139:chemically induced
chemical_list: D044966:Anti-Retroviral Agents; D011480:Protease Inhibitors