CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

TUESDAY, FEBRUARY 24, 2015 Session P-T7 Poster Session

Poster Hall

2:30 pm– 4:00 pm Pharmacokinetics and Safety of ART During Pregnancy 891 Raltegravir Plasma Concentrations on HIV-1 Infected Pregnant Women Emilie Belissa; Amine Benchikh; Charlotte Charpentier; MorganeValentin; Agnes Bourgeois-Moine; Sylvie Lariven; Florence Damond;YazdanYazdanpanah; Sophie Matheron; Gilles Peytavin APHP, Bichat-Claude Bernard Hospital, Paris, France Background: Raltegravir (RAL) is used in association with other antiretrovirals (ARV) in pregnant women as a formal tritherapy or an additional ARV as intensification in late presenters or in low level viremia. Because of physiological changes during pregnancy, RAL plasma concentration 12 hours post-dose (C12h) at different trimester of pregnancy is important to evaluate. Secondary objectives are assessment of efficacy and safety of RAL containing regimen during pregnancy Methods: single center, observational, descriptive study. The main inclusion criteria were pregnant women treated with RAL 400mg BID containing regimen with available demographic, immuno-virological and therapeutic data. ARV maternal plasma and cord blood concentrations were performed using UPLC-MS/MS. All results were expressed as median [IQR25-75%] and Mann-Whitney test was used Results: among the 23 women enrolled (31 yrs, 19 African), 11 of them received RAL as intensification of ongoing ARV treatment. Their characteristics were: duration of HIV infection 8.3 yrs (4.0-12.1); Plasma HIV-RNA (pVL) before ARV 32,365 c/mL (3,792-200,500), before RAL 544 c/mL (156-13,232) and before pregnancy 184 c/mL (35-17,650); Nadir CD4 224/mm 3 (42-352) and CD4 before pregnancy 434/mm 3 (280-529), duration of ARV 7.1 yrs (1.1-11.7); duration of RAL 8.1 months (2.6-67.1). All patients received RAL+PI/ r+NRTIs except one (RAL+ABC/3TC). PI/r were: DRV/r (17), LPV/r (4) and SQV/r (1). RAL C12h at 2 nd and 3 rd trimesters was 84ng/mL (32-215, n=20) and 58ng/mL (20-185, n=47) (p=0.52), respectively. Cord blood/maternal plasma concentrations ratio (R CB/MP ) was 1.03 (0.50-1.43, n=4). The mode of delivery was available in 16 women (10 caesarians). At delivery, 18 of 23 patients had pVL<50c/mL and all pVL<400c/mL. Among the 5 women with detectable pVL, 2 was non adherent and 3 late presenters. Neonate characteristics were: gestational age 38.7 weeks (38.1-40.1; n=20), Hb 16,4 g/dL (15,1-17.9; n=9), bilirubinemia 30 m mol/L (21-36; n=7). No neonate was HIV infected. No adverse event was observed in mothers and neonates during the follow-up Conclusions: RAL plasma concentrations are not modified during pregnancy and are similar with historical data in non pregnant population. Besides, RAL containing regimen seems to be efficient and safe for mother and her children, probably due to a favorable placental transfer (R CB/MP >1.0) 892 Etravirine Pharmacokinetics During Pregnancy and Postpartum Brookie M. Best 1 ; Angela Colbers 2 ; JiajiaWang 3 ; GrahamTaylor 4 ; Alice Stek 5 ; Marjo van Kasteren 6 ; Mark Mirochnick 7 ; David Burger 2 On behalf of the IMPAACT P1026s ProtocolTeam and the PANNA Network 1 University of California San Diego, San Diego, CA, US; 2 Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 3 Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, US; 4 Imperial College Healthcare NHS Trust, London, United Kingdom; 5 University of Southern California School of Medicine, Los Angeles, CA, US; 6 St. Elisabeth Hospital, Tilburg, Netherlands; 7 Boston University School of Medicine, Boston, MA, US Background: Maintaining therapeutic concentrations of antiretrovirals (ARVs) throughout pregnancy is critical to prevent perinatal transmission and maternal resistance development. Physiological changes during pregnancy may alter the pharmacokinetics (PK) of prescribed medicines, particularly those metabolized by cytochrome (CYP) P450 enzymes. To date, no studies have reported etravirine (ETV) PK during pregnancy. ETV is metabolized by and inhibits or induces CYP 3A4, 2C9 and 2C19. The goal was to determine ETV PK parameters during the 2 nd and 3 rd trimesters compared to the same subjects postpartum and to historical non-pregnant controls. Methods: P1026s is an ongoing, multi-center, multi-arm, prospective PK study of HIV-1 infected pregnant women on ARVs for routine care. This arm enrolled women on ETV 200 mg twice daily. The PANNA Study is a similar design, enrolling in European countries. Steady-state 12-hour ETV profiles were obtained in the 2 nd and 3 rd trimesters, and at 4-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. The P1026s target steady-state ETV 12-hour AUC was 2.5 μ g*hr/mL (10 th percentile in non- pregnant historical controls). The 50 th percentile AUC in non-pregnant controls is 4.2 μ g*hr/mL, and a suggested minimum concentration from the GRACE trial is 0.16 mg/L. Paired PK parameters were compared with the Wilcoxon signed-rank test at a significance of p<0.05. Results: Five, 12 and 8 women completed 2 nd trimester, 3 rd trimester, and postpartum PK evaluations. Median (range) age was 26 (19-43) years. Seven patients were black; 6 Hispanic; and 1 Caucasian. At delivery 9/10 patients had an HIV viral load <50 copies/mL. One subject took ETV 400 mg once daily; her oral clearance (CL/F), AUC 0-12 , and half-life values are included in the summary data, while individual concentrations were excluded. ETV PK parameters are presented below. The median (range) ratio of cord blood/maternal plasma concentrations (n=5) was 0.59 (0.19-4.25). Six children were HIV uninfected; for five children results are pending.

Poster Abstracts

537

CROI 2015