KONCERT A Kaletra ONCE Daily Randomised Trial of the Pharmacokinetics, Safety and Efficacy of Twice-daily Versus Once-daily Lopinavir/Ritonavir Tablets Dosed by Weight as Part of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-1 (HIV-1) Infected Children (PENTA 18)

Inclusion Criteria:

• aged <18 years (up to 18th birthday) with confirmed HIV-1 infection

• weight ≥15 kg

• able to swallow tablets

• stable (i.e. CD4 not declining) on a combination antiretroviral regimen that hasincluded lopinavir/ritonavir for at least 24 weeks

• taking lopinavir/ritonavir dosed twice-daily and be willing at the screening visit tochange to tablet formulation (if not currently taking tablets) and to change thelopinavir/ritonavir dose to follow the recommended FDA dosing plan based on bodyweight bands as necessary (see 7.2.2); if participating in the PK study*, be willingat the screening visit to change to lopinavir/ritonavir half strength formulationtablets (100/25mg) only, dosed twice-daily and change the lopinavir/ritonavir dose tofollow the recommended FDA dosing plan based on body weight bands as necessary (see 7.2.1)

• viral suppression (HIV-1 RNA <50 copies/ml) for at least the prior 24 weeks (minimumof 2 measurements).

• children and caregivers willing to participate in the PK study if they are among aminimum of the first 16 children enrolled in each body weight band in the trial,including a second PK assessment if randomised to switch to once-dailylopinavir/ritonavir.

• parents/carers and children, where applicable, give informed written consent

Exclusion Criteria:

• children on an antiretroviral regimen that includes a non-nucleoside reversetranscriptase inhibitor (NNRTI), fosamprenavir or nelfinavir

• children who have previously failed virologically on a protease inhibitor (PI)containing regimen (where virological failure is defined as two successive HIV-1 RNAresults>1000 copies/ml (confirmed) more than 24 weeks after starting highly activeantiretroviral therapy (HAART), i.e changes for toxicity are not counted as failure)

• acute illness

• abnormal renal or liver function (grade 3 or above)

• receiving concomitant therapy except for prophylaxis; Some treatments may be allowed,but must first be discussed with a trial medical expert

• pregnancy or risk of pregnancy in females of child bearing potential