Abstract Body

IMPAACT P1093 is an ongoing Phase I/II multicenter, open-label, pharmacokinetic (PK), safety, dose finding study of dolutegravir (DTG) plus optimized background regimen (OBR) in children and adolescents in age defined cohorts. The pediatric weight band dosing of ~1 mg/kg once a day in adolescents achieved PK exposure comparable to those observed at 50 mg once daily in adults.

Cohort IIA enrolled HIV infected treatment experienced, integrase naive children >6 to <12 years of age with an HIV RNA of ≥1000 copies/mL (c/mL) into Stage 1 (intensive PK) or Stage 2 (no PK, safety and efficacy). In Stage 1, DTG was added to a stable, failing ARV regimen, with OBR optimization after intensive PK (~Day 5-10); in Stage 2, DTG and OBR at study entry. Safety, tolerability, CD4 cell count and HIV-1 RNA were evaluated at Week 48,a primary objective. Virologic success was defined as achieving an HIV-1 RNA <400 c/mL by Week 48 based on the FDA snapshot algorithm and HIV-1 RNA <50 c/mL as a secondary outcome.

Twenty three children (Stage 1, n=11; Stage 2, n=12) were enrolled and 21 (91.3%) completed the 48 week study visit. Demographics were as follows: 70% (16/23) male; 52% (12/23) African American, 17% (4/23) Caucasian; 26% (6/23) were of Hispanic ethnicity. Median age (range) was 10 yrs (6, 11) and median weight (range) was 30.0 kg (18, 54). Median (IQR) baseline CD4+ cell count and % were 645 cells/mm3 (466, 732) and 24% (14.3%, 28.7%), respectively. Median (IQR) baseline HIV-1 RNA log10 was 5.0 log10 c/mL (4.5, 5.5). DTG weight band target dose was 1 mg/kg, (# participants/dose (mg)) distribution as follows: 1 (70); 5 (50); 6 (35); 8 (25). Virologic success (wk 48): HIV RNA < 400 c/mL was achieved in 78.3 % (18/23); 95% CI: (56.3 % to 92.5%); HIV <50 c/m achieved in 73.9% (17/23); 95% CI: (51.6% to 89.8%).  Median (IQR) gain in CD4 cell count and % at Week 48 was 387 cells/mm3 (49, 575) and 9% (7 14), respectively. DTG was well tolerated; none of the four Grade 3 clinical adverse events nor three Grade 3 laboratory events were study drug related.  Two subjects went off study: one for virologic failure, and one moved and was lost to follow-up.  There were no Grade 4 AEs, SAEs or discontinuations due to AEs.

DTG plus OBR was safe, well tolerated and provided virologic efficacy through week 48 in HIV infected children 6-12 years of age.