A PROSPECTIVE-STUDY OF THE EFFECT OF IV PENTAMIDINE THERAPY ON VENTRICULAR ARRHYTHMIAS AND QTC PROLONGATION IN HIV-INFECTED PATIENTS

Study objectives: IV pentamidine therapy in HIV-infected patients has been associated in case reports and one uncontrolled prospective serie s with frequent prolongation of the rate-corrected QT interval (QTc) a nd a high risk for potentially lethal ventricular arrhythmias, especia lly torsade de pointes. The aim of this study was to prospectively exa mine in a controlled manner the effect of IV pentamidine therapy on th e QT interval and the incidence of ventricular arrhythmias. Design: Op en, nonrandomized, prospective evaluation of ventricular arrhythmia in cidence in HIV-infected patients receiving pentamidine or trimethoprim -sulfamethoxazole (TMP-SMX) utilizing Holter monitoring prior to and d uring therapy with these agents. Setting: Staten Island University Hos pital, Staten Island, NY. Patients: Twenty-seven HIV-infected patients , of whom 16 received IV pentamidine and 11 received IV TMP-SMX. Measu rements and results: Study patients underwent Holter monitoring prior to therapy and during the first 3 days and last 2 days of therapy with pentamidine or TMP-SMX, 12-lead ECG prior to and every 24 to 48 h, se rum electrolytes prior to and on days 3, 6, 9, and 12 of therapy, and baseline transthoracic two-dimensional and Doppler echocardiography. I n the pentamidine group, the results for each monitoring period were a s follows (means are presented +/- SEM): pretherapy, 1.66 +/- 1.03 (me dian = 0) premature ventricular complexes (PVCs) per hour, zero nonsus tained ventricular tachycardia (NSVT), zero sustained ventricular tach ycardia (VT); early therapy, 1.55 +/- 0.91 (median = 0.04) PVCs per ho ur, two NSVT (both less than or equal to 5 complexes), zero sustained VT; late therapy, 1.69 +/- 1.17 (median = 0.08) PVCs per hour, zero NS VT, zero sustained VT (p value not significant for early or late thera py as compared to pretherapy for PVCs per hour, NSVT, or sustained VT) . In the TMP-SMX group, the Holter monitoring results were as follows: pretherapy, 1.36 +/- 1.27 (median = 0) PVCs per hour, zero NSVT, zero sustained VT; early therapy, 0.71 +/- 0.53 (median = 0.03) PVCs per h our, two NSVT, zero sustained VT; late therapy, 0.56 +/- 0.51 (median = 0) PVCs per hour, zero NSVT, zero sustained VT (p value not signific ant for pretherapy, early therapy, or late therapy with TMP-SMX as com pared to pentamidine for PVCs per hour, NSVT, or VT). The QTc also did not significantly differ during therapy with pentamidine as compared to TMP-SMX. The mean QTc in the pentamidine group decreased during the rapy as compared to pretherapy with the difference approaching signifi cance for days 2, 4, and 6 with pentamidine (p < 0.06). Conclusions: Q Tc prolongation during therapy with pentamidine in HIV-infected patien ts is not as frequent an occurrence as has been reported previously. I n the absence of QTc prolongation, pentamidine therapy was not associa ted with a significant increase in PVCs, NSVT, or sustained VT as comp ared to pretherapy recordings or as compared to therapy with TMP-SMX.