CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

initiated at 1 μg/mL. Safety evaluations included echocardiograms (ECHOs) at baseline and weeks 1 and 6, and electrocardiograms at baseline, day 5, and weeks 1, 2, and 6. Adverse events (AE) were classified as expected (associated with prematurity) or unexpected. Results: Twenty-five newborns were enrolled;13 (52%) male and 22 (88%) black African. The median (interquartile range (IQR)) birth weight and gestational age were 2130 (1775, 2630) grams and 35 (32, 37) weeks, respectively. The median (IQR) age at enrollment was 45 (35, 61) days old. As of August 2017, 22 newborns contributed to 124 LPV concentrations. Median C0 was 4.7 (IQR 1.5, 7.4) µg/mL, with 1.5 and 4 hour levels approximately 1.5-2 times higher, similar to adults. LPV C0 was above target in 41/50 samples (figure 1). Of the 24 newborns with safety data, 11 had Grade 3/4 unexpected AEs (none treatment related) and four newborns had Grade 3/4 expected AEs. Most AEs were infection related (n=11). One infant died from presumed sepsis on day 2 of LPV/r. Infant ECHOs were normal except for two with mild abnormalities. No abnormal PR or QTc interval prolongation was observed. Median serum osmolality post LPV/r initiation was 289 (IQR 287, 291) mOsm/kg. Conclusion: No treatment related adverse events were observed in this study of LPV/r safety and PK in newborns and very young infants. LPV concentrations were similar to adult levels, with most C0 >1 μg/mL.

(5 deaths). Baseline and WK 48 VL available in 220 children (49% female; 11% ART naïve,84% switched from LPV/r and 5% from NVP based ART). At Baseline, median (IQR) age in months was 20 (8-41) in ARV naïve, 47 (32-66) in LPV/r exposed and 50 (41-67) in NVP exposed, while VL results: Median VL (log 10 cp/ ml) and %with VL<50, <400 and <1000 cp/ml were 5.4 (4.7-5.8), 3.5%, 9.5% and 11.3% respectively in naïve, 2.2 (1.6-3.9), 29.5%, 57.9% and 63.5% in LPV/r exposed and 4.7 (4.3-5.4), 5.3%, 10.6% and 10.6% in the NVP exposed. At WK48, VL parameters were 2.1 (1.3-3.8),43.5%, 65.2% and 70% respectively in naïve,1.6(1.3-2.1), 56%, 80.9% and 85.1% in LPV/r exposed and 1.5(1.3-2.5), 58.3%, 75% and 83.3% in the NVP exposed. At baseline, Immunodeficiency, wasting and stunting were present in 70%, 50% and 35% of naïve respectively, 33%, 17% and 7.8% of LPV/r and in 40%, 20% and 14.3% of NVP exposed, reaching 36.4%, 9% and 5% of naïve, 21.7%, 2% and 3%% of LPV/r exposed and 40%, 0%, and 14.3% of NVP exposed respectively at Wk48. 21 children had 67 AEs grade 3/4, 2 leading to treatment stoppage. Conclusion: LPV/r pellets were well accepted with minimal safety concerns. Naïve, those failing NVP, as well as those switching from LPV/r liquid were well suppressed at week 48 and had recuperated immunologically and clinically.

Poster Abstracts

843 SAFETY, PK, & EFFICACY OF FTC/TAF IN HIV-INFECTED ADOLESCENTS (12-18 YRS) Janet Chen 1 , Xavier Saez-Llorens 2 , Elizabeth Castaño 2 , Faeezah Patel 3 , Ann Melvin 4 , Elizabeth J. McFarland 5 , Jaime G. Deville 6 , Mark Cotton 7 , Chrisna Andersen 8 , Heather Maxwell 9 , Mingjin Yan 9 , Sophia R. Majeed 9 , Erin Quirk 9 , Hiba Graham 9 , Cheryl Pikora 9 1 Drexel College of Medicine, Philadelphia, PA, USA, 2 Hospital del Niño, Panama City, Panama, 3 Empilweni Service and Research Unit, Johannesburg, South Africa, 4 Seattle Children’s Hospital, Seattle, WA, USA, 5 University of Colorado, Aurora, CO, USA, 6 University of California Los Angeles, Los Angeles, CA, USA, 7 Tygerberg Hospital, Cape Town, South Africa, 8 Be Part Yoluntu Centre, Paarl, South Africa, 9 Gilead Sciences, Inc, Foster City, CA, USA Background: Fixed-dose combination emtricitabine (FTC)/tenofovir alafenamide (TAF) is approved for adolescents (US, EU) and a recommended first-line NRTI backbone for adolescents (US). Safety and efficacy of TAF in adolescents has been demonstrated in studies of elvitegravir/cobicistat/FTC/ TAF, including favorable bone and renal safety. Safety, pharmacokinetics (PK), and efficacy of other FTC/TAF-containing regimens in adolescents have not been reported. We describe safety, PK and efficacy of FTC/TAF in combination with boosted or unboosted third antiretroviral (ARV) agents to adolescents. Methods: This open-label, 2-part, 48-week (W) trial evaluated switching from 2 NRTIs to FTC/TAF while remaining on various third ARV agents (eg efavirenz or lopinavir/ritonavir). Virologically suppressed adolescents (12 to <18 yrs) weighing ≥35 kg were enrolled and given FTC/TAF 200/10 mg or 200/25 mg, with boosted or unboosted third ARVs, respectively. Adverse events (AE), laboratory tests (eg renal biomarkers) and bone mineral density (BMD) were assessed. Intensive PK was evaluated at W2. Efficacy was evaluated as proportion of adolescents with plasma HIV-1 RNA <50 copies(c)/mL (snapshot algorithm). We report safety, PK and efficacy through W24. Results: We treated 28 adolescents; median age 14 yrs (range 12-17), median weight 45 kg (range 35-62), 43% female, 43% Black. Median (Q1, Q3) duration of exposure to study drug was 76 (56, 129) wks. Mean study drug adherence was high (93%). Most common AE was viral upper respiratory infection (32%). Two participants had serious, unrelated AEs. Five had AEs related to study drug; none discontinued study drug due to an AE. Mean % change from baseline in BMD at W24 was +3.9% for spine and +2.2% for total body less head (TBLH). Mean change in BMD height-age adjusted Z-score was 0.00 for spine and -0.03

842 EFFECTIVENESS AND SAFETY OF LPV/R PELLETS-BASED ART IN CHILDREN: 48-WEEK ANALYSIS Isabelle Andrieux-Meyer 1 , Olawale Salami 1 , Raymond Omollo 1 , Dalton

Wamalwa 2 , Elizabeth Maleche Obimbo 2 , Adeodata Kekitiinwa 3 , Juliet Mwanga- Amumpaire 4 , Patrick Oyaro 5 , Elizabeth A. Bukusi 6 , Moses Waweru 1 , Monique Wasunna 1 , Janice Lee 1 , François Simon 1 , Marc Lallemant 1 1 Drug for Neglected Diseases Initiative, Geneva, Switzerland, 2 University of Nairobi, Nairobi, Kenya, 3 Baylor College of Medicine Children’s Foundation, Kampala, Uganda, 4 Epicentre, Mbarara, Uganda, 5 Kenya Medical Research Institute, Kisumu, Kenya, 6 Kenya Medical Research Institute, Nairobi, Kenya Background: A palatable, heat-stable, easy-to-administer pellets’ formulation of LPV/r has received tentative USFDA approval for use in infants and young children. However, there are few data on its effectiveness and safety in routine care. The LIVING study evaluates the effectiveness, safety, PK and acceptability of LPV/r pellets + ABC/3TC (or AZT/3TC) dispersible tablets, in HIV+ children unable to swallow tablets in Kenya and Uganda. Methods: An open-label, single-arm, prospective, multi-centre, phase-3b implementation study. Inclusion criteria: ARV naïve, on liquid LPV/r-based or failing NNRTI based ART; Weight ≥3 and <25kg. ART dosing based on WHO weight bands. Children assessed at baseline, 1 month then 3-monthly. Effectiveness was defined as a composite of VL<1000copies/ml, no death and being on study drugs. AEs were graded using DAIDS tables. Stunting was defined as height-for-age <-2SD, wasting as weight for height <-2SD and immunodeficiency following WHO age-specified CD4% cut offs. Results: As of 31/07/17, 610 patients had been enrolled, of whom 378 and 223 had reached WK24 and WK48 respectively, with a cohort retention of 88.7%

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