Study of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1

Prior treatment

• Acute hepatitis within 30 days prior to screening.
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.
• Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor throughout the study.
• Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.3.1.
• An opportunistic illness indicative of Stage 3 HIV diagnosed within 30 days prior to screening (as defined in Appendix 11.9).
• Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening.

Other illness

• Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed).
• Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B virus (HBV) core antibody (antibody against hepatitis B core antigen [anti-HBc]) at screening. If a participant is negative for HBsAg and positive for anti-HBc but HBV DNA is undetectable, the participant may be enrolled.
• A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
• Known hypersensitivity to the study drug, its metabolites, or formulation excipient.

Lab values

• Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study: CD4 cell count < 200 cells/mm3.

Other

• Current alcohol or substance use judged by the investigator to potentially interfere with the participant’s study compliance.
• CD4 percentage < 20%.
• Life expectancy ≤ 1 year.

• Participants must meet all of the following inclusion criteria to be eligible for participation in this study: Parent, guardian, or legally authorized representative willing and able to provide written informed consent prior to performing study procedures as required by local country regulations.
• Lactating people must agree to discontinue nursing before administration of the study drugs.
• Participant willing and able to provide written assent if possible (in accordance with their local institutional guidelines and local country regulations).
• Age and body weight at screening: Cohort 1: ≥ 12 years to < 18 years weighing ≥ 35 kg Cohort 2: ≥ 6 years to < 12 years weighing ≥ 25 kg to < 35 kg Cohort 3: ≥ 2 years to < 6 years weighing ≥ 10 kg to < 25 kg
• On a complex ARV regimen. Complex regimens are any ART that is not a STR taken once daily (eg, > 1 tablet or any other formulation a day).
• Documented plasma HIV-1 RNA levels must be < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is < 50 copies/mL) in the last 6 months prior to screening (at least 1 measure prior to screening).
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• No documented or suspected resistance to INSTIs (mutations T66A/I/K, E92G/Q/V, G118R, F121C/Y, G140R, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
• The following laboratory parameters at screening: a) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 using Bedside Schwartz formula. b) Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3). c) Hemoglobin ≥ 85 g/L (> 8.5 g/dL). d) Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3). e) Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 5 x upper limit of normal. f) Total bilirubin ≤ 23 µmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 µmol/L (≤ 0.4 mg/dL).
• Negative serum beta-human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test at Day 1 for participants assigned female at birth of childbearing potential only (as defined in Appendix 11.5).