A Trial of Lopinavir/Ritonavir Dosed According to the Who Pediatric Weight Band Dosing Guidelines

This is a Phase II/III trial to assess the short-term pharmacokinetics, safety, and
tolerance of LPV/r in HIV-infected infants and children initiating LPV/r therapy who weigh
>3 and <25 kg and are dosed according to the WHO antiretroviral (ARV) weight band dosing
guidelines. LPV/r will be administered as the heat-stable pediatric LPV/r 100/25 mg tablet
in children who can swallow tablets or the liquid 80/20 mg/mL formulation in children who
cannot swallow tablets. LPV/r will be dosed according to the WHO ARV weight band dosing
schedule as part of a combination ARV regimen including two NRTIs as background therapy. The
NRTI background will be prescribed by the health care provider according to local national
and/or international guidelines for treatment of HIV-infected children. LPV/r will be
provided as part of the study.

The study duration, on treatment, will be 24 weeks.

Inclusion Criteria:

Weight greater than or equal to 3kg and less than or equal to 25 kg at the time of
enrollment.

Past or current documentation of a confirmed diagnosis of HIV-1 infection defined as two
positive assays from two different samples. At least one of the specified assays must be
performed in an AIDS Clinical Trials Group (ACTG)/ International Maternal Pediatric
Adolescent AIDS Clinical Trials Group (IMPAACT) certified laboratory. The two results may
be in any combination of the following:

LPV/r-treatment naïve and LPV/r-treatment eligible as defined by country-specific
guidelines or the WHO pediatric treatment guidelines confirmed by investigator.

Willingness to take two NRTIs, in accordance with appropriate national or international
treatment guidelines.

Demonstrated ability and willingness to swallow tablets for children greater than 10 kg.

Note # 1: This can be assessed before inclusion (for example, a test trial with similar
size solid tablet such as tic-tac).

Note # 2: Subjects on the weight band 10-16.9 kg that are unable to swallow tablets will
receive liquid formulation.

Parent or legal guardian able and willing to provide written informed consent.

Exclusion Criteria:

Planned concurrent use of nonnucleoside reverse transcriptase inhibitor (NNRTI), integrase
inhibitors, or entry inhibitor.

Planned concurrent PI use, other than LPV/r.

Prior treatment with LPV/r (prior treatment with other PIs is allowed).

Any of the following laboratory tests within 30 days prior to study entry classified as
greater than or equal to Grade 3 (see Division of AIDS [DAIDS] Table for Grading the
Severity of Adult and Pediatric Adverse Events, Version 1.0 [December 2004], Clarification
August, 2009, http://rcc.tech-res-intl.com): neutrophil count, hemoglobin, platelets, AST,
ALT, or serum creatinine.

A greater than or equal to Grade 2 lipase or clinical evidence of pancreatitis within 30
days prior to study entry.

Tuberculosis co-treatment with rifampicin-containing regimen.

Treatment with any enzyme-inducing antiepileptic drugs (such as phenobarbital, phenytoin
or carbamazepine).

Clinical condition requiring the use of a prohibited medication

Clinically unstable child requiring acute treatment for a serious opportunistic infection.

Chemotherapy for active malignancy.

Any clinically significant diseases (other than HIV-1 infection) or clinically significant
findings during the screening medical history or physical examination that, in the
investigator's opinion, would compromise participation in this study.

Treatment with experimental drugs for any indication within 30 days prior to study entry.

Known history of cardiac conduction abnormality and/or underlying structural heart
disease, including congenital long QT.