Safety of and Immune Response to GSK1349572 in HIV-1 Infected Infants, Children, and Adolescents

Inclusion Criteria:

• At least 4 weeks but younger than 18 years of age at study entry
• Confirmed HIV-1 infection defined as positive results from two samples collected at different time points (see protocol for more information)

• For antiretroviral (ARV) treatment-experienced participants (includes those who have received therapy to interrupt maternal-infant transmission) currently not on antiretroviral therapy (ART):

  1. Must be off treatment for at least 4 weeks, AND
  2. Must have an HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening

• For ARV treatment-experienced participants currently on ART:

  1. Must be on an unchanged, failing therapeutic regimen for at least 8 to 12 weeks before screening (less than or equal to 1 log drop in HIV-1 RNA within the previous 8 to 12 weeks before screening), AND
  2. Must have an HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening.

(Note: Dose adjustments for growth or formula substitutions [i.e., switching from single agent to fixed dose combination] are permitted during this 8 to 12 week time frame. Substitutions of one ARV within the same class for toxicity or tolerability management, or discontinuation of ARVs are also allowed during within 8 to 12 weeks.)

• Demonstrated ability or willingness to swallow assigned study medications (tablets or pediatric formulation) (Note: Tablets MAY NOT be crushed or dissolved)
• Parent or legal guardian able and willing to provide signed informed consent
• Female participants who are of childbearing potential and who are engaging in sexual activity that could lead to pregnancy must use two adequate birth control methods while on study and for 2 weeks after stopping study drug; hormonal birth control alone (e.g., pills, shots, or slow-release inserts placed under/on the skin) would not be considered adequate; an effective, medically accepted barrier method of contraception (e.g., female/male condoms, diaphragm or cervical cap with a cream or gel that kills sperm [excluding nonoxydyl-9], intrauterine device [IUD], others) also must be used during the study; condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV-1 transmission
• Males engaging in sexual activity that could lead to HIV-1 transmission must use a condom
• Participants must have available at least one fully active drug for the planned optimized background regimen (OBR). Historical genotypes obtained within 1 year of screening will be considered by the study team for determination of fully active drugs if screening genotype testing is inconclusive.

Exclusion Criteria:

• Presence of any active AIDS-defining opportunistic infection
• Known Grade 3 or greater of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, aspartate aminotransferase (AST),alanine transaminase (ALT), lipase, serum creatinine, total bilirubin. A single repeat within the 30 days is allowed for eligibility determination. (Note: Grade 3 or greater total bilirubin is allowable if the participant is on ATV.)
• Any known Grade 4 laboratory toxicities within 30 days prior to study entry. (Note: Grade 4 total bilirubin is allowable if the participant is one ATV.)
• The following liver toxicities within 30 days prior to study entry: ALT greater than 3X the upper limit of normal (ULN) AND direct bilirubin greater than 2X the ULN.
• Any prior history of malignancy, with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin
• Clinical or symptomatic evidence of pancreatitis, as determined by the clinician
• Use of any disallowed medications at time of screening (more information can be found in the protocol)
• Known history of exposure to integrase inhibitor treatment by the participant or participant's mother prior to delivery/cessation of breastfeeding
• Known resistance to an integrase inhibitor
• Pregnancy or breastfeeding (Note: Infants who are receiving breast milk are eligible to enroll)
• Participant is currently participating in or has participated in a study with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from both study teams is granted
• Participant is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study to a non-IMPAACT study site
• Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
• Participant has used, or anticipates using, chronic systemic immunosuppressive agents or systemic interferon (e.g., for treatment of hepatitis C virus [HCV] infection) within 30 days prior to beginning GSK1349572 study treatment. Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (less than or equal to 30 days) are permitted. See protocol for more information on disallowed medications.
• Any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
• Any ARV-treatment naïve participant
• Active tuberculosis (TB) disease and/or requirement for treatment that includes rifampin at the time of the screening visit. However, participants who need rifampin treatment while on GSK1349572 will be allowed to continue in the study provided the GSK1349572 dose is adjusted according to the protocol.