Table 2.
Artemisinin Pharmacokinetics Following a 6-Dose Regimen of Artemether-Lumefantrine in Human Immunodeficiency Virus (HIV)-Uninfected and HIV-Infected Children
| Pharmacokinetic Parameter | HIV-Uninfected |
HIV-Infected |
Ratio (P Value) |
||||
|---|---|---|---|---|---|---|---|
| No ART (n = 51a) | EFV (n = 31) | LPV/r (n = 30b) | NVP (n = 30) | EFV/No ART | LPV/No ART | NVP/No ART | |
| Artemether | |||||||
| Cmax, ng/mL | 35.3 (28.0–44.5) | 15.3 (11.2–21.1) | 26.4 (19.1–36.4) | 10.2 (7.6–13.8) | 0.43 (.0006) | 0.75 (.23) | 0.29 (<.0001) |
| Tmax, h | 2.0 (.7–3.0) | 2.1 (1.1–4.0) | 3.0 (1.1–4.0) | 2.1 (1.1–3.1) | 1.1 (.22) | 1.5 (.18) | 1.1 (.29) |
| AUC0–8h, h × ng/mL | 120 (97.6–147) | 48.5 (37.2–63.1) | 89.7 (68.6–117) | 36.3 (27.8–47.4)c | 0.40 (<.0001) | 0.75 (.16) | 0.30 (<.0001) |
| C24h, ng/mL | 1.2 (.7–1.7) | BLQ (BLQ–.8) | 1.2 (.6–2.5) | BLQ (BLQ–1.1) | <1 (<.0001) | 0.98 (.96) | <1 (<.0001) |
| DHA | |||||||
| Cmax, ng/mL | 66.9 (53.6–83.5) | 24.0 (18.0–32.0) | 55.3 (41.3–74.1) | 45.5 (34.1–60.8) | 0.36 (<.0001) | 0.83 (.39) | 0.68 (.08) |
| Tmax, h | 2.9 (2.0–3.1) | 3.0 (1.1–4.0) | 3.0 (2.0–4.1) | 2.2 (2.0–4.0) | 1.0 (.75) | 1.0 (.99) | 0.80 (.31) |
| AUC0–8h, h × ng/mL | 212 (176–256) | 62.9 (49.2–80.3)c | 171 (133–219) | 137 (107–175) | 0.30 (<.0001) | 0.81 (.25) | 0.65 (.02) |
| C8h, ng/mL | 6.5 (4.6–8.0) | 1.2 (.6–3.4) | 9.3 (4.6–16.5) | 4.5 (2.9–8.8) | 0.19 (<.0001) | 1.42 (.16) | 0.681 (.41) |
| AUC ratio (DHA/AR) | 1.7 (1.3–2.5) | 1.6 (.8–2.2) | 1.9 (1.5–3.4) | 4.1 (2.2–6.9) | 0.94 (.07) | 1.12 (.74) | 2.41 (<.0001) |
Data are presented as geometric mean (90% confidence interval) unless otherwise specified. Significance level: α = .0083 (0.05/6); Tmax, C8h, and C24h reported as median (interquartile range); mixed-models repeated-measures analysis to compare between all groups using log-transformed geometric means.
Abbreviations: AR, artemether; ART, antiretroviral therapy; AUC, area under the concentration-time curve; BLQ, below the limit of quantitation; Cmax, maximal concentration; DHA, dihydroartemisinin; EFV, efavirenz; HIV, human immunodeficiency virus; LPV, lopinavir; NVP, nevirapine; r, ritonavir; Tmax, time to maximal concentration.
a n = 53 for C24h, n = 49 for C8h.
b n = 29 for C8h.
c One subject in the group did not have sufficient points for AUC8h due to being below the lower limit of quantification; AUC last was used.