The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age

This study will examine the pharmacokinetics (PK), safety, and tolerability of fixed-dose
combination abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC) dispersible and immediate
release tablets in HIV-1-infected children less than 12 years of age.

Children will be enrolled into one of five ABC/DTG/3TC dosing groups based on their weight.
The first 5-7 children within each weight-band will undergo intensive PK assessments 5-10
days after starting ABC/DTG/3TC to confirm dose selection. Children will remain on their
initial dose of ABC/DTG/3TC through Week 4. After Week 4, ABC/DTG/3TC dosing will be adjusted
based on PK results at the individual or weight-band level, and/or an individual child's
growth and weight gain over time.

Follow-up study visits for all participants will occur at Weeks 1, 4, 12, 24, 36, and 48.
Some participants may attend additional study visits at Weeks 2, 6, 8, 16, and/or 20. Study
visits may include physical examination, study drug adherence and tolerability
questionnaires, blood collection, and intensive PK sampling. Following the Week 48 study
visit, some children may continue on the study for up to 144 weeks.

Inclusion Criteria:

- Less than 12 years of age at entry

- Weight 6 kg to less than 40 kg at entry

- Antiretroviral therapy (ART)-naïve at entry or has been taking a stable ART regimen
for at least six consecutive months at entry

- Note: For ART-naïve children, receipt of antiretroviral (ARV) prophylaxis prior
to diagnosis of HIV infection is permitted. For these children, ascertainment of
this criterion may be based on parent or guardian report only, but available
medical records should also be reviewed in relation to this criterion.

- Note: For ART-experienced children (on a stable ART regimen), dose and
formulation changes (e.g., for growth) within the six months prior to entry are
permitted. For these children, ascertainment of this criterion must be based on
medical records.

- For ART-experienced children (on a stable ART regimen), has had a suppressed HIV viral
load (HIV-1 RNA less than 200 copies/mL) for at least six consecutive months prior to
entry

- Note: To fulfill this criterion, at least two documented HIV-1 RNA results less
than 200 copies/mL must be available, one based on a specimen collected at least
six months prior to entry and one based on a specimen collected within 30 days
prior to entry.

- Note: Any documented HIV-1 RNA result greater than or equal to 200 copies/mL
based on a specimen collected within six months prior to entry is exclusionary
(see exclusion criterion below).

- At screening, has normal, Grade 1, or Grade 2 laboratory test results for all of the
following, based on testing of specimens collected within 30 days prior to entry and
grading per the Division of AIDS Table for Grading the Severity of Adult and Pediatric
Adverse Events (refer to the study protocol for guidance on severity grading):

- Hemoglobin (greater than or equal to 8.5 g/dL or greater than or equal to 5.25
mmol/L)

- Absolute neutrophil count (greater than or equal to 600 cells/mm^3 or greater
than or equal to 0.600 x 10^9 cells/L)

- Platelet count (greater than or equal to 50,000 cells/mm^3 or greater than or
equal to 50.00 x 10^9 cells/L)

- Estimated glomerular filtration rate (eGFR; bedside Schwartz formula; greater
than or equal to 60 ml/min/1.73 m^2)

- Alanine transaminase (ALT) (less than 5.0 x ULN)

- Aspartate aminotransferase (AST) (less than 5.0 x ULN)

- Total bilirubin (less than 2.6 x ULN)

- Direct bilirubin (less than or equal to ULN)

- Note: Laboratory tests may be repeated during the screening period (i.e., within
30 days prior to entry), with the latest results used for eligibility
determination.

- Note: For treatment-experienced children on an atazanavir-containing ART regimen,
Grade 3 or higher total bilirubin is permitted.

- Confirmed HIV-1-infection based on documented testing of two samples collected at
different time points:

- Sample #1 may be tested using any of the following:

- Two rapid antibody tests from different manufacturers or based on different
principles and epitopes

- One enzyme immunoassay OR Western Blot OR immunofluorescence assay OR
chemiluminescence assay

- One HIV DNA polymerase chain reaction (PCR)

- One quantitative HIV RNA PCR (above the limit of detection of the assay)

- One qualitative HIV RNA PCR

- One HIV total nucleic acid test

- Sample #2 may be tested using any of the following:

- Rapid antibody test. If this option is used in combination with two rapid
tests for Sample #1, at least one of the three rapid tests must be United
States Food and Drug Administration (FDA)-approved, and the third rapid test
must be from a third manufacturer or based on a third principle or epitope.

- One enzyme immunoassay OR Western Blot OR immunofluorescence assay OR
chemiluminescence assay

- One HIV DNA PCR

- One quantitative HIV RNA PCR (above the limit of detection of the assay)

- One qualitative HIV RNA PCR

- One HIV total nucleic acid test

- Whole blood, plasma, or serum samples must be tested. If both samples are tested
using antibody tests, at least one of the samples must be tested in a laboratory
that operates according to Good Clinical Laboratory Practice guidelines and
participates in an appropriate external quality assurance program. If nucleic
acid testing is used, at least one test must be performed in a Clinical
Laboratory Improvement Amendments (CLIA) certified (for US sites) or Virology
Quality Assurance (VQA) certified (for non-US sites) laboratory. For tests
performed in other settings, adequate source documentation including the date of
specimen collection, date of testing, test performed, and test result must be
available. FDA approved testing methods should be used when possible.

- HLA-B*5701-negative based on documented testing at any time prior to entry

- Note: Documented testing is required even if the potential participant has
received ABC prior to study entry.

- For females of reproductive potential (defined as having experienced menarche), not
pregnant based on testing performed at screening

- For females of reproductive potential who are engaging in sexual activity that could
lead to pregnancy, willing to use two methods of contraception while receiving study
drug, based on participant and parent or guardian report at entry

- One of the two methods must be highly effective; highly effective methods include
surgical sterilization (i.e., hysterectomy, bilateral oophorectomy, tubal
ligation, or salpingectomy) and the following:

- Contraceptive intrauterine device or intrauterine system

- Subdermal contraceptive implant

- Progestogen injections

- Progestogen only oral contraceptive pills

- Combined estrogen and progestogen oral contraceptive pills

- Percutaneous contraceptive patch

- Contraceptive vaginal ring

- The highly effective method must be initiated prior to study entry. The second
method should ideally be a barrier method. Male or female condom use is
recommended with all other methods of contraception for dual protection against
pregnancy and to avoid transmission of HIV and other sexually transmitted
infections.

- Based on parent or guardian report at entry, child is expected to be available for 48
weeks of follow-up

- Parent or guardian is willing and able to provide written informed consent for child's
study participation and, when applicable per local institutional review board/ethics
committee (IRB/EC) policies and procedures, child is willing and able to provide
written informed assent for study participation

Exclusion Criteria:

- Less than two years of age at entry

- Note: This age restriction reflects ViiV's currently agreed Pediatric
Investigative Plan (PIP) and Pediatric Study Plan (PSP). If these plans are
modified in the future, such that regulatory agreement is obtained to evaluate
ABC/DTG/3TC in children less than two years of age, this restriction will be
removed via a protocol Clarification Memorandum. Upon issuance of the
Clarification Memorandum, study sites will be permitted to enroll children less
than two years of age.

- Documented resistance to ABC, DTG, or 3TC

- Note: Testing to rule out resistance is not required, and the M184V resistance
mutation is not exclusionary.

- For ART-experienced children (on a stable ART regimen), documented HIV-1 RNA result
greater than or equal to 200 copies/mL based on a specimen collected within six months
prior to entry

- History of any of the following as determined by the site investigator based on
participant/parent/guardian report and available medical records:

- Malignancy (ever)

- Hypersensitivity reaction to ABC (ever)

- Receipt of any prohibited medication (refer to the study protocol for more
information) within 30 days prior to study entry

- Receipt of systemic interferon or any chronic systemic immunosuppressant
medication within 30 days prior to study entry

- Note: Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg)
taken for replacement or short course therapy are permitted. Intranasal or
inhaled steroid use is also permitted.

- Has any of the following as determined by the site investigator based on
participant/parent/guardian report and available medical records

- Current clinical evidence of pancreatitis

- Currently-active tuberculosis (TB) and/or currently receiving
rifampicin-containing TB treatment

- Currently-active AIDS-defining (WHO Clinical Stage 4) opportunistic infection

- Has any documented or suspected clinically significant medical condition or any other
condition that, in the opinion of the site investigator, would make participation in
the study unsafe, complicate interpretation of study outcome data, or otherwise
interfere with achieving the study objectives