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  50th ICAAC
Boston, MA
September 12-15, 2010
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Associations between Protease Inhibitors (PIs) and QTc and PR Interval Durations in the Strategies for Management of Antiretroviral Therapy (SMART) Trial - poster pdf attached
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Reported by Jules Levin
ICAAC Sept 2010 Boston
E Z Soliman1, J D Lundgren2, M P Roediger3, D A Duprez4, Z Temesgen5 , M Bickel6 , J C Shlay7, C Somboonwit8, P Reiss9, J H Stein10, J D Neaton3 for the INSIGHT SMART Study Group 1Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest University School of Medicine, USA; 2Copenhagen HIV Programme (CHIP), National University Hospital and University of Copenhagen, Denmark; 3Division of Biostatistics, School of Public Health, University of Minnesota, USA ; 4Departments of Medicine, University of Minnesota, USA; 5Mayo Clinic and Foundation, Division of Infectious Diseases, USA; 6HIV Medical Treatment and Research Unit, JW Goethe University, Germany; 7Denver Community Programs for Clinical Research on AIDS, USA; 8Division of Infectious Disease & International Medicine Division of Infectious Disease & International Medicine, University of South Florida College of Medicine, USA;9Department of Medicine, Amsterdam Institute for Global Health and Development and Center for Infection and Immunity, Academic Medical Center, the Netherlands; 10School of Medicine and Public Health, University of Wisconsin School of Medicine and Public Health, USA
There are contradictory reports - based on case series and single site studies - regarding the effects of protease inhibitors (PIs) on the electrocardiographic (ECG) measures of QT and PR interval durations. The effect of interrupting use of PIs on QT and PR progression is also unknown. The SMART study, with its large sample size, standardized ECG collection methodology and centrally automated ECG reading, serves as a unique source of data to asses whether use of PIs (compared with NNRTIs) is associated with these ECG abnormalities, and whether interruption of Antiretroviral Therapy (ART) reverses them.
This analysis included 3,719 participants from the SMART study, of whom 1,879 were randomised to receive intermittent antiretroviral therapy [drug conservation (DC) group], while the rest received these drugs continuously [viral suppression (VS) group](Figure 1). Linear regression analysis was used to compare four boosted PI regimens (SQV/r, LPV/r, ATV/r, and other PI/r), and non-boosted PI regimens with NNRTI (no PI) regimens for Bazett's (QTcB) and Fridericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF and PR after 12 and 24 months of randomisation were compared in the DC group and VS group.
Table 1 shows baseline characteristics stratified by ART use. Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms (Table 2). At study entry, 49% of participants were taking an NNRTI (no PI)-based regimen and 31% were prescribed a boosted PI (PI/r), the most common being lopinavir (LPV/r). After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted PI group (p=0.26 and p=0.34, respectively). For those given any of the boosted PIs, QTcB was 1.5 ms lower than the NNRTI group (p=0.04) (Table 3). Both boosted and non-boosted PI-containing regimens were significantly associated (p<0.01 for each) with longer PR intervals compared to the NNRTI group (Table 3). After adjustment, the difference between boosted PIs and the NNRTI group was 5.11 ms (p<0.01); for non-boosted PIs, this difference was 3.00 ms (p<0.01) (Table 3). Following ART interruption, PR duration declined for both the boosted and non-boosted PI groups and compared to the VS group, significant changes in PR interval were observed 24 months after ART interruption of boosted PIs (p<0.01) (Table 4).
Different PI-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All PI-based regimens (boosted and non-boosted) were associated with prolongation of PR, and interruption of PI regimens reduced the prolonged PR duration. Further studies are needed to confirm the findings of this study, preferably using a randomised study design.