Table 2.
Determinants of day 7 lumefantrine concentrations in non-pregnant patients treated with the six-dose artemether-lumefantrine regimen
| N (n)a | Change (%) (95 % CI) | P value | |
|---|---|---|---|
| Univariable model | |||
| Dose (mg/kg) | 2,551 | 0.3 (0.1 to 0.6) | 0.010 |
| Co-administration with fat | 2,574 (2,185) | −1.0 (−28.2 to 26.2) | 0.943 |
| Unsupervised administrationb | 2,574 (816) | −45.4 (−50.6 to −39.6) | <0.001 |
| Age | |||
| < 1 year | 82 | −37.7 (−50.5 to −21.6) | <0.001 |
| 1–2 years | 562 | −46.5 (−53.5 to −38.5) | <0.001 |
| 3–4 years | 597 | −26.1(−35.7 to −15.1) | <0.001 |
| 5–11 years | 534 | −3.4 (−12.6 to 6.9) | 0.507 |
| 12+ years | 799 | Reference | |
| Sample matrix | |||
| Capillary bloodc | 848 | −38.2 (−54.0 to −22.4) | <0.001 |
| Venous bloodc | 544 | 18.5 (−34.7 to 71.8) | 0.458 |
| Venous plasma | 1,182 | Reference | |
| Day of samplingd | 2,574 | −36.8 (−56.6 to −17.0) | 0.004 |
| Fevere | 2,426 (1,054) | −17.4 (−24.0 to −10.8) | <0.001 |
| Hemoglobinf | 2,200 | 1.0 (−0.8 to 2.8) | 0.272 |
| Baseline parasitemia (log10) | 2,554 | −8.8 (−13.3 to −4.1) | <0.001 |
| WAZg | 1,240 | 3.2 (−1.7 to 8.0) | 0.191 |
| UWAh | 1,240 (215) | −4.5 (−19.1 to 10.2) | 0.559 |
| Multivariable modeli | |||
| Dose (mg/kg) | 2,422 | 0.5 (0.2 to 0.7) | 0.001 |
| Unsupervised administrationb | 2,422 (795) | −43.8 (−49.1 to −38.0) | <0.001 |
| Day of samplingd | 2,422 | −36.4 (−53.6 to −12.9) | 0.005 |
| Fevere | 2,422 (1,052) | −13.5 (−20.1 to −6.4) | <0.001 |
| Baseline parasitemia (log10) | 2,422 | −5.1 (−9.8 to −0.1) | 0.045 |
| Age | |||
| < 1 year | 82 | −38.1 (−51.1 to −21.7) | <0.001 |
| 1–2 years | 555 | −41.4 (−48.9 to −32.7) | <0.001 |
| 3–4 years | 594 | −20.9 (−30.9 to −9.4) | 0.001 |
| 5–11 years | 508 | −6.6 (−16.1 to 4.0) | 0.215 |
| 12+ years | 683 | Reference | |
| Multivariable model – supervised administration onlyj | |||
| Dose (mg/kg) | 1,562 | 0.4 (0.1 to 0.7) | 0.007 |
| Day of samplingd | 1,562 | −43.0 (−60.1 to −18.6) | 0.001 |
| Sample matrixk | |||
| Capillary bloodc | 366 | −15.2 (−31.0 to 4.3) | 0.119 |
| Venous bloodc | 541 | 1.4 (−23.2 to 34.0) | 0.921 |
| Venous plasma | 655 | Reference | |
| Hemoglobin | |||
| Capillary bloodc | 366 | −5.4 (−9.0 to −1.7) | 0.005 |
| Venous bloodc | 541 | 2.4 (−1.5 to 6.4) | 0.229 |
| Venous plasma | 655 | −1.8 (−4.2 to 0.7) | 0.163 |
| Fevere | 1,562 (590) | −12.2 (−19.3 to −4.4) | 0.003 |
| Baseline parasitemia (log10) | 1,562 | −6.1 (−10.7 to −1.4) | 0.012 |
| Age | |||
| < 3 years old UWAh | 28 | −52.8 (−65.0 to −36.5) | <0.001 |
| Not UWA | 262 | −38.6 (−47.5 to −28.2) | <0.001 |
| 3–4 years old UWAh | 48 | −19.5 (−35.8 to 1.0) | 0.061 |
| Not UWA | 229 | −17.5 (−29.4 to −3.6) | 0.015 |
| 5–11 years old | 399 | −2.0 (−11.5 to 8.5) | 0.881 |
| ≥ 12 years old | 596 | Reference | |
aN, total number of patients with non-missing data; n, number of patients with this characteristic; bunsupervised administration includes five studies with no supervised doses and two studies with the three morning doses supervised; ccollected on filtered paper; dper day, evaluated between days 6 and 8; edefined as axillary temperature >37.5 °C on enrolment; fno statistically significant association was found when stratified by sample matrix; P for interaction = 0.435; gWorld Health Organization (WHO) Child Growth Standards weight-for-age Z-score (WAZ) in children <5 years of age; hdefined using a WAZ < −2 in children <5 years of age; i151 out of 2,574 patients were excluded from this model due to missing information on dose (23) and fever (148); j131 out of 1,758 patients with supervised treatment were excluded from this model due to missing information on dose (3), fever (127), UWA status (1) or hemoglobin (65); kcomparison at mean value of hemoglobin of 11 g/dL