The purpose of this study is to examine 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.
Name: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets
Name: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release)
Description: Based on analysis of intensive PK samples collected at Week 1 and compared within each weight band to the PK targets specified in the study protocol
Measure: Geometric mean area under the plasma concentration-time curve over 24 hours at steady-state (AUC0-24h) for ABC, DTG, and 3TC Time: Measured at Week 1Description: Based on analysis of intensive PK samples collected at Week 1
Measure: Geometric mean maximum plasma concentration (Cmax) for ABC, DTG, and 3TC Time: Measured at Week 1Description: Based on analysis of intensive PK samples collected at Week 1 and compared within each weight band to the PK targets specified in the study protocol
Measure: Geometric mean concentration at 24 hours post-dose (C24h) for ABC, DTG, and 3TC Time: Measured at Week 1Description: Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Number of participants who had adverse events Time: Measured through Week 24Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had Grade 3 or Grade 4 adverse events assessed as related to study drug Time: Measured through Week 24Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had Grade 5 adverse events assessed as related to study drug Time: Measured through Week 24Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had life-threatening adverse events assessed as related to study drug Time: Measured through Week 24Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had serious adverse events assessed as related to study drug Time: Measured through Week 24Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had adverse events assessed as related to study drug that lead to permanent discontinuation of study drug Time: Measured through Week 24Description: Derived from population PK modeling with sampling
Measure: Area under the plasma concentration-time curve over 24 hours at steady-state (AUC0-24h) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Derived from population PK modeling with sampling
Measure: Concentration at time 0 (pre-dose) (C0h) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Derived from population PK modeling with sampling
Measure: Concentration at 24 hours post-dose (C24h) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Derived from population PK modeling with sampling
Measure: Maximum plasma concentration (Cmax) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Derived from population PK modeling with sampling
Measure: Time to maximum concentration (Tmax) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Derived from population PK modeling with sampling
Measure: Apparent oral clearance (CL/F) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Derived from population PK modeling with sampling
Measure: Half-life (t1/2) for ABC, DTG, and 3TC Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had adverse events Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had Grade 3 or Grade 4 adverse events assessed as related to study drug Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had Grade 5 adverse events assessed as related to study drug Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had life-threatening adverse events assessed as related to study drug Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had serious adverse events assessed as related to study drug Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had adverse events assessed as related to study drug that lead to permanent discontinuation of study drug Time: Measured through Week 48Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had adverse events Time: Measured through Week 144Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had Grade 3 or Grade 4 adverse events assessed as related to study drug Time: Measured through Week 144Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had Grade 5 adverse events assessed as related to study drug Time: Measured through Week 144Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had life-threatening adverse events assessed as related to study drug Time: Measured through Week 144Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had serious adverse events assessed as related to study drug Time: Measured through Week 144Description: Based on DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017
Measure: Number of participants who had adverse events assessed as related to study drug that lead to permanent discontinuation of study drug Time: Measured through Week 144Description: Based on laboratory evaluations
Measure: Proportion of participants with HIV-1 RNA levels meeting virologic response criteria Time: Measured through Week 48Description: Based on laboratory evaluations
Measure: Proportion of participants with HIV-1 RNA levels meeting virologic response criteria Time: Measured through Week 144Description: Based on laboratory evaluations
Measure: Number of participant with HIV-1 RNA greater than or equal to 200 copies/mL at Weeks 4, 24, and 48 (snapshot algorithm) Time: Measured through Week 48Description: Based on laboratory evaluations
Measure: Number of participants with HIV-1 RNA greater than or equal to 50 copies/mL at Weeks 4, 24, and 48 (snapshot algorithm) Time: Measured through Week 48Description: Based on laboratory evaluations
Measure: Median changes (with IQR) in CD4+ cell count and percentage at Weeks 4, 24, and 48 Time: Measured through Week 48Description: Based on laboratory evaluations
Measure: Median changes (with IQR) in CD4+ cell count and percentage through Week 144 Time: Measured through Week 144Description: Based on laboratory evaluations
Measure: Median changes (with IQR) in total cholesterol, HDL, LDL, and triglycerides at Weeks 24 and 48 Time: Measured through Week 48Description: Based on questionnaire responses
Measure: Aggregated data on parent/guardian reported adherence to study drug at Weeks 4, 24, and 48 Time: Measured through Week 48Description: Based on questionnaire responses
Measure: Aggregated data on parent/guardian reported tolerability (i.e., palatability and acceptability) of study drug at Weeks 4, 12, 24, and 48 Time: Measured through Week 48Description: Based on laboratory evaluations
Measure: ARV resistance mutations at time of virologic failure (and at entry for children with resistance identified at time of virologic failure) Time: Measured through Week 48Allocation: Non-Randomized
Parallel Assignment
There is one SNP
- Based on parent or guardian report at entry, child is expected to be available for 48 weeks of follow-up - Parent or legal 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: - Documented resistance to ABC, DTG, or 3TC - Note: Testing to rule out resistance is not required, and the M184V resistance mutation is not exclusionary. --- M184V ---