Table 3.
Clinical events of ECG findings from included studies.
| PR interval | QRS Wave | QT interval | ||||||||||
| Author | Antiviral | Before treatment | During treatment | After treatment | Before treatment | During treatment | After treatment | Before treatment | During treatment | After treatment | Clinical events related to ECG abnormalities induced by antiviral agents | Incidence for ECG abnormality |
| Baker et al (2006)[26] | LPV/r (400 mg/100 mg, twice daily for 7 days, n = 9) | N.R | N.R | N.R | N.R | N.R | N.R | Baseline QTcB for LPV/r = 407 (SE: 5.8)Baseline QTcB for RTV = 409 (SE: 5.8)After receiveing Brupenorphine/Naloxone for 2 weeks = 410 ± 2.6 | N.R | QTcB 2 hour post-dose on day 7 for LPV/r = 413 (SE: 6.1)Mean change from baseline = 6.14 (95% CI: –5.97–18.25), P > .05 | N.R | 0% |
| RTV (100 mg, twice daily for 10 days, n = 10) | QTcB 2 hour post-dose on day 10 for RTV = 419 (SE: 5.9)Mean change from baseline = 9.38 (95% CI: –2.36–21.12), P > .05 | |||||||||||
| Busti et al (2006)[22] | ATV (300 mg once daily for 1 month, n = 2) or ATV/r (300 mg/100 mg once daily for 1 month, n = 19) | 176 ± 30 | 2 hours after first dose (±SD) = 173 ± 33, P = .11 | After 1 month (± SD) = 184 ± 34, P = .005 | 87 ± 6.5 | 2 hours after first dose (± SD) = 90 ± 9.4, P = .005 | After 1 month (± SD) = 91 ± 7.2, P = .001 | QT interval (± SD) = 388 ± 28.4QTcB (± SD) = 404.6 ± 16.4QTd (± SD) = 28.5 ± 13 | QT interval:2 hour after first dose (±SD) = 372 ± 25.8, P = .002QTcB interval:2 hours after first dose (± SD) = 407.8 ± 15.2, P = .084QTd Interval:2 hours after first dose (n = 16, ± SD) = 23.4 ± 14, P = .197 | QT interval:After 1 month (± SD) = 386 ± 28.6, P = .74QTcB interval:After 1 month (± SD) = 403 ± 14.5, P = .434QTd Interval:After 1 month (± SD) = 26.3 ± 12.6, P = .865 | N.R | PR interval > 200 ms after 1 month of ATV/r = 16% (approximately based on upper value of one standard deviation) |
| Sarapa et al (2008)[23] | RTV (100 mg, single dose) | N.R | N.R | N.R | N.R | N.R | N.R | QTcF = 373.3–449.7QTcB = 371.7–458.0 | N.A | 6 hours after first dose:QTcF change = 0.16 (90% CI: –1.38–1.69), P > .05QTcB change = 0.73 (90% CI: –1.29–2.75), P > .0512 hours after first dose:QTcF change = –1.04 (90%CI: –2.98–0.90), P > .05QTcB change = –0.44 (90%CI: –2.76–1.87), P > .05 | N.R | 0% |
| Rathbun et al (2009)[27] | Group of Arm A:Day 1–6 = ATV/r (300 mg/100 mg, daily)Day 7–16 = ATV (300 mg daily) and LPV/r(400 mg/100 mg twice daily)Day 17–20 = ATV (300 mg daily) and LPV/r (800 mg/200 mg daily)Group of Arm B:Day 1–6 = LPV/r (400 mg/100 mg twice daily)Day 7–12 = LPV/r (400 mg/100 mg twice daily) and ATV (300 mg daily) | 145 ± 14 | Combined results of both group:Day 16, Arm A + Day 12, Arm B (± SD) = 159 ± 21, P < .05Day 20, Arm A + Day 12, Arm B (± SD) = 162 ± 24, P < .05 | Combined results of both group:30 days follow up (± SD) = 144 ± 13, P > .05 | 92 ± 10 | Combined results of both group:Day 12, Arm B + Day 16, Arm A (±SD) = 97 ± 10, P < .01Day 12, Arm B + Day 20, Arm A (± SD) = 97 ± 12, P < .01 | Combined results of both group:30 days follow up (± SD) = 91 ± 8, P > .05 | N.R | N.R | N.R | Arm A:Left bundle branch block after 10 days ATV and LPV/r coadministration (32-year-old man)Arm B:First degree atrioventricular block after 6 days ATV and LPV/r coadministration (40-year-old man) | Left bundle branch block after 10 days of ATV and LPV/r coadministration = 1 out of 8 patients (12.5%)First degree atrioventricular block after 6 days of ATV and LPV/r coadministration = 1 out of 8 patients (12.5%) |
| Byakika-Kibwika et al (2011)[24] | LPV/r (400 mg/100 mg, for 1 month) | N.R | Mean PR interval after first dose of artemeter-lumefantrine + LPV/r:LPV/r arm vs ART naïve arm (± SD) = 154 ± 18.4 vs 169 ± 15.9, P = .02 | N.R | N.R | Mean QRS wide after first dose of artemeter-lumefantrine + LPV/r:LPV/r arm vs ART naïve arm (±SD) = 87.4 ± 6.6 vs 82.8 ± 6.6, P = .06 | N.R | QTcB median:LPV/r arm vs ART naïve arm (IQR) = 415 (403–439) vs 395 (388–425) | QTcB median after first dose of artemeter-–lumefantrine dosing + LPV/r:LPV/r arm vs ART naive arm (IQR) = After 12h: 415 (404–439) vs 419 (403–427), P = .7 | QTcB median after first dose of Artemeter-Lumefantrine + LPV/r:LPV/r arm vs ART naive arm (IQR) = After 24h: 424 (401–434) vs 406 (393–411), P = .02After 48h: 411 (396–432) vs 409 (401–419), P = .7After 72h: 424 (416–441) vs 408 (392–417), P = .04 | N.R | 0% |
| Zhang et al (2012)[28] | Group A:SQV/r (1000 mg/100 mg, twice daily, for 3 days) | N.R | N.R | Mean maximum prolongation at 4-h post dose on day 3 = 25 msPR interval > 200, % Subjects in 3 days = 40% | N.R | N.R | N.R | QTc < 450 (female)QTc < 430 (male) | N.R | QTcS 12-h post dose on day 3, mean maximum increase = 18.9 (Upper 95% CI = 22.0)QTcS interval > 450–480, % Subjects in 3 days = 11% | 16 participants reported 23 events of syncopeor presyncope with 74% events (17 out of 23) were reported while receiving SQV/r regimens. | PR interval > 200 ms in 3 days after SQV/r (1000 mg/100 mg, twice daily) = 40%QTcS interval > 450–480 ms in 3 days after SQV/r (1000 mg/100 mg, twice daily) = 11% |
| Group BSQV/r (1500 mg/100 mg, twice daily, for 3 days) | Mean maximum prolongation at 5-h post dose on day 3 = 34 msPR interval >200, % Subjects in 3 days = 47% | QTcS 20-h post dose on day 3, mean maximum increase = 30.2 (Upper 95% CI = 33.4)QTcS interval >450–480, % Subjects in 3 days = 18%QTcS interval > 480 – 550, % Subjects in 3 days = 2% | PR interval > 200 ms in 3 days after SQV/r (1500 mg/100 mg, twice daily, for 3 days) = 47%QTcS interval > 450–480 ms in 3 days after SQV/r (1500 mg/100 mg, twice daily) = 18%QTcS interval > 480–550 ms in 3 days after SQV/r (1500 mg/100 mg, twice daily) = 2% | |||||||||
| Boffito et al (2015)[29] | Day 1–7 = SQV/r (500 mg/100 mg, twice daily)Day 8–14 = SQV/r (1000 mg/100 mg, twice daily) | N.R | Change of PR interval at every 4 hours post-dose:Day 3 (± SD) = 5 ± 9Day 4 (± SD) = 2 ± 9Day 7 (± SD) = 5 ± 6Day 10 (± SD) = 8 ± 8 | Change of PR interval at 4 hours hour post-dose on day 14 (95% CI) = 9 ± 7 | N.R | Change of QRS wave at 0 hour hour post-dose:Day 3 (± SD) = 1 ± 3Day 4 (± SD) = 1 ± 3Day 7 (± SD) = 2 ± 4Day 10 (± SD) = 3 ± 3 | Change of QRS wave at 0 hour hour post-dose on day 14 (± SD) = 2 ± 4 | N.R | Change of QTcF interval at 2 hours post-dose:Day 3 (± SD): 3 ± 7Day 4 (± SD): 1 ± 9Change of QTcF interval at 6 hours post-dose:Day 7 (±SD): 7 ± 7Day 10 (±SD): 12 ± 12 | Change of QTcF interval at 6 hours post-dose on day 14 (±SD) = 7 ± 8 | N.R | 0% |
| Vicente et al (2019)[25] | LPV/r (800 mg/200 mg, twice daily, for 3 days) (n = 50) | 162.3 ± 16.5 | Change of PR interval after first dose on day 1 = 14.8 [90% CI: 10.3–19.4] | Change of PR interval after first dose on day 3 = 33.5 [90% CI: 22.7–44.4] | 87.1 ± 5.8 | Change of QRS wave after first dose on day 1 = –0.2 [90% CI: –3.5–3.1] | Change of QRS wave after first dose on day 3 = 4.0 [90% CI: –0.4–8.5] | QTcF = 383.9 ± 17.1 | N.R | N.R | N.R | 0% |
| Cao et al (2020)[30] | LPV/r (400 mg/100 mg, twice daily, for 14 days) | N.R | N.R | N.R | N.R | N.R | N.R | N.R | Day 14 = 1.1% (1 out of 95 patients) of LPV/r treatment group has QT Prolongation | N.R | Unconsciousness (1.1%) | QT prolongation in LPV/r treatment group = 1 out of 95 patients (1.1%) |