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The World Health Organization (WHO) recommends weight band dosing of antiretrovirals for children. Data are limited describing drug exposure/safety of lopinavir/ritonavir using WHO weight band dosing.International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1083 was a phase II/III trial assessing the pharmacokinetics (PK) and short-term safety, tolerance and efficacy of lopinavir/ritonavir in human immunodeficiency virus–infected children 3–25 kg dosed according to WHO weight bands, with liquid solution or meltrex extrusion tablets. The main PK target was an area under the curve (AUC0–24) of 80–320 μg·h/mL.Of 97 enrolled participants, median age 2.5 years, 89 (91.8%) completed the protocol. Median LPV dose was 303 mg/m2. The geometric mean (90% confidence limits) LPV PK AUC0–24 was 196 (177–217) μg·h/mL and Cmin was 2.47 (1.52–4.02) μg/mL. AUC0–24 was within the target range for 79% of participants. The median (Q1, Q3) difference between individual observed PK parameters and those expected if Food and Drug Administration dosing guidelines were followed was 30.7 (7.9, 54.3) for AUC0–24 and 0.56 (0, 1.27) for Cmin. Ten (10%) participants had grade 3 or 4 events deemed related to study treatment, mostly asymptomatic laboratory abnormalities. Three participants died of unrelated study treatment causes. At week 24, 57 of 79 (72%) participants reached viral suppression and the median increase in CD4% (n = 83) was 6.0 (P < 0.0001).WHO weight band dosing guidelines in children achieved adequate LPV plasma exposure but was higher than that expected with Food and Drug Administration dosing guidelines. Despite the higher LPV exposure, the treatment was well tolerated and the 24-week efficacy data were favorable.