Electrocardiogram abnormalities with atazanavir and lopinavir/ritonavir.
OBJECTIVE
Concurrent atazanavir (ATV) and lopinavir/ritonavir (LPV/r) may be useful for patients with extensive antiretroviral resistance; however, limited information exists concerning the pharmacokinetics and safety of this combination.


METHODS
A parallel-arm pharmacokinetic study was conducted in HIV-infected patients (n = 10) using contemporary formulations of each agent. Intensive pharmacokinetics were conducted at Day 6 (ATV/r), Day 16 (ATV qd + LPV/r bid), and Day 20 (ATV + LPV/r qd) in Arm A and Day 6 (LPV/r) and Day 12 (LPV/r bid + ATV qd) in Arm B. Plasma ATV, LPV, and ritonavir concentrations were measured by HPLC-UV. Electrocardiograms (12-lead) and safety labs were conducted at each visit.


RESULTS
Prolonged PR and QRS intervals occurred in the majority of patients (mean increase: 16 ms and 5 ms, respectively; p < or = .01). Two patients developed new-onset arrhythmias (bundle branch block, atrioventricular block), resulting in premature termination of the study. No change in ATV or LPV pharmacokinetics was evident.


CONCLUSIONS
Concurrent ATV and LPV/r was associated with PR and QRS interval changes in this small study population. Electrocardiogram monitoring should be considered for patients receiving concurrent ATV and LPV/r shortly after their initiation, especially if other risk factors for altered conduction are present.
Rathbun
Chris R
CR
Department of Clinical and Administrative Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, USA. chris-rathbun@ouhsc.edu
Liedtke
Michelle D
MD
Blevins
Steve M
SM
Harrison
Donald
D
Lockhart
Staci M
SM
Salvaggio
Michelle
M
Acosta
Edward P
EP
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D000069446:Atazanavir Sulfate; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D011725:Pyridines / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D019438:Ritonavir / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors
D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir