CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

compared to typical concentrations seen in adults receiving 200 mg NVP BID and 150 mg 3TC BID and the frequency of therapeutic NVP troughs (>3 mcg/mL) determined. Data are presented as mean (range). Results: Six infants born at GA 37 (35-39), starting therapy at age 2.8 (1-5) days and weighing 3.12 (2.30-3.50) kg were evaluated. All infants experienced a reduction in HIV RNA and none had any adverse events considered related to ART during the first month of life. One participant was non-adherent at Week 2 with NVP and 3TC levels that were below the limit of quantitation (BLQ). Excluding the BLQ result, NVP levels averaged 5.10 (1.74-10.95) mcg/mL, and 3TC levels averaged 195 (114-368) ng/mL, obtained 14.2 (13.1-16.8) hrs after the prior dose (Figure 1). At Week 2, all NVP levels in adherent subjects were 3-11 mcg/mL. Conclusions: Therapeutic, but not excessive, NVP levels are achieved in term infants receiving 6mg/kg BID during the first weeks of life. This dose appears to be well tolerated and should be utilized for very early treatment initiation in term and near term infants.

816 IMPAACT 1093: Dolutegravir in 6- to 12-Year-Old HIV-Infected Children: 48-Week Results AndrewWiznia 1 ; Carmelita Alvero 2 ;Terry Fenton 3 ; Kathleen George 4 ; EllenTownley 5 ; Rohan Hazra 6 ; Bobbie Graham 7 ; Annie Buchanan 8 ; CindyVavro 9 ; RolandoViani 10 ; for the IMPAACT P1093 Study Group 1 Albert Einstein Coll of Med, Bronx, NY, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 SDAC, Harvard Sch of PH, Boston, MA, USA; 4 IMPAACT Operations, Durham, NC, USA; 5 NIH, Rockville, MD, USA; 6 Eunice Kennedy Shriver NICHD, Bethesda, MD, USA; 7 Frontier Sci & Tech Rsr Fndn, Inc, Buffalo, NY, USA; 8 GSK, Research Triangle Park, NC, USA; 9 ViiV Hlthcare, Research Triangle Park, NC, USA; 10 Univ of California San Diego, San Diego, CA, USA Background: 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. Methods: 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. Results: 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/mm 3 (466, 732) and 24% (14.3%, 28.7%), respectively. Median (IQR) baseline HIV-1 RNA log 10 was 5.0 log 10 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/mm 3 (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. Conclusions: DTG plus OBR was safe, well tolerated and provided virologic efficacy through week 48 in HIV infected children 6-12 years of age. 817 Safety and Efficacy of E/C/F/TAF in HIV-1 Infected Treatment-Naïve Adolescents Aditya Gaur 1 ; Hilda Kizito 2 ; Rana Chakraborty 3 ; Jagmohan Batra 4 ; Pope Kosalaraksa 5 ;Wicharn Luesomboon 6 ;Yongwu Shao 7 ; Devi SenGupta 7 ; Martin S. Rhee 7 ; Erin Quirk 7 1 St Jude Children’s Rsr Hosp, Memphis, TN, USA; 2 Joint Clinical Rsr Cntr, Kampala, Uganda; 3 Emory Univ, Atlanta, GA, USA; 4 Miller Children’s Hosp, Long Beach, CA, USA; 5 Khon Kaen Univ, Khon Kaen, Thailand; 6 Queen Savang Vadhana Memorial Hosp, Chon Buri, Thailand; 7 Gilead Scis, Inc, Foster City, CA, USA Background: A subset of Tenofovir DF (TDF) recipients may have renal and bone toxicities. Tenofovir alafenamide (TAF), a novel prodrug of tenofovir shows 91% lower plasma tenofovir levels compared to TDF. In phase 3 adult studies, a single tablet regimen of elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and TAF 10mg (E/C/F/TAF) was highly efficacious and well-tolerated, with improved renal and bone safety profiles as compared to TDF-containing regimens. We previously reported favorable pharmacokinetics of E/C/F/TAF in HIV-1 infected treatment-naïve adolescents through Week 24 and now report the safety and efficacy through the preplanned secondary efficacy endpoint at 48 weeks. Methods: Treatment-naïve adolescents (12 to <18 years) with CD4 > 100 cells/mm 3 , weighing ≥35 kg received open-label E/C/F/TAF for 48 weeks. The primary efficacy endpoint was virologic success (HIV-1 RNA <50 c/mL) at Week 24 using the snapshot algorithm. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: 50 adolescents enrolled and two discontinued prior to Week 48. At Week 48, 46/50 (92%) had HIV-1 RNA < 50 copies/mL. The mean (SD) increase in CD4 cell count was 224 (170) cells/μL. No subject developed antiretroviral resistance. The most commonly reported adverse events (AEs) were mild/moderate and unrelated to study treatment. No subjects discontinued study drug due to AE, and none had proximal renal tubulopathy. The median (Q1, Q3) change in serum creatinine (Cr) was +0.07 (0.02, 0.15) mg/dL, consistent with the inhibition of renal tubular Cr secretion by cobicistat. The median (Q1, Q3) percent change from baseline to week 48 in urine protein to Cr ratio, retinol binding protein to Cr ratio, and beta-2-microglobulin to Cr ratio were -27% (-55%, +19%), -22% (-46%, +22%), and -29% (-60%, -4%), respectively. The median (Q1, Q3) change in spine BMD was +3.3% (+0.8%, +7.1%) and that of total body less head (TBLH) BMD was +0.9% (-0.5%, +2.6%). The median (Q1, Q3) change in height-adjusted spine Z-score was -0.03 (-0.16, +0.20) and that of TBLH Z-score was -0.09 (-0.3, +0.07). One subject had a ≥4% decrease in spine BMD from baseline, and none had a TBLH BMD decrease of ≥4%. Conclusions: E/C/F/TAF is an effective first-line therapy and is well-tolerated with favorable renal and bone safety profiles in HIV-1 infected adolescents. These findings support further evaluation of E/C/F/TAF in younger HIV-1 infected pediatric patients.

Poster Abstracts

341

CROI 2016