TABLE 2.

Piperaquine pharmacokinetic parameters for participants in step 1^a

PK parameter	Valuesb for participants in the following study groups:				NVP/ART-naive participants		LPV/r/ART–naive participants		EFV/ART-naive participants
	ART naive (n = 6)	NVP (n = 5)c	LPV/r (n = 6)	EFV (n = 6)	Geometric mean ratio (90% CI)	P valued	Geometric mean ratio (90% CI)	P value	Geometric mean ratio (90% CI)	P value
AUC0–28 days (ng · h/ml)	33,385 (26,131–42,652)	43,632 (31,383–60,662)	38,300 (27,256–53,802)	18,914 (14,144–25,291)	1.31 (0.86–1.99)	0.290	1.15 (0.75–1.76)	0.589	0.57 (0.38–0.83)	0.029
Cmax (ng/ml)	350 (252–485)	637 (453–897)	327 (263–406)	253 (156–412)	1.82 (1.13–2.94)	0.061	0.94 (0.63–1.39)	0.775	0.72 (0.40–1.32)	0.371
tmax (h)	3 (2–60)	4 (3–5)	60 (60–60)	3 (2–60)		0.573e		0.049e		1.000e
t1/2 (h)f	332 (174–631)	319 (262–388)	455 (186–1,114)	227 (120–432)	0.36 (0.49–1.89)	0.915	1.37 (0.44–4.31)	0.636	0.68 (0.36–1.30)	0.658

^aART, antiretroviral therapy; NVP, nevirapine-based ART; EFV, efavirenz-based ART; LPV/r, ritonavir-boosted lopinavir-based ART; C_max, maximum concentration, t_max, the time to reach the maximum concentration, t_1/2, drug elimination half-life; AUC_{0–28 days}, area under the concentration-time curve from days 0 to 28; C_d7, day 7 piperaquine concentration.

^bValues are presented as the geometric mean (90% confidence interval) for all PK parameters except t_max, the values of which are given as the median (interquartile range).

^cOne participant did not complete follow-up and was excluded from the analysis.

^dP values were calculated using analysis of variance (ANOVA) in STATA (version 15.0) (α = 0.1), unless indicated otherwise.

^eThis P value was calculated using the Wilcoxon rank-sum test (α = 0.05).

^fHalf-life estimation excluded values below the lower limit of quantification for each participant.