CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

PK results of BMS-626529 when coadministered with DRV/r and/or ETR Conclusions: BMS-663068 can be co-administered with DRV/r or DRV/r + ETR, without dose adjustment. Co-administration with ETR (without DRV/r) resulted in a ~50% decrease in BMS-626529 C 12 levels. Skin rash was consistent with ETR and DRV/r administration.

THURSDAY, FEBRUARY 26, 2015 Session P-H4 Poster Session

Poster Hall

2:30 pm– 4:00 pm Pharmacokinetics in Compartments and Reservoirs and of Novel Formulations 524 Local and Systemic Pharmacokinetic Profile of Dapivirine Vaginal Ring-004When Used Continuously Over Various Periods up to TwelveWeeks Annalene M. Nel 1 ;Wouter Haazen 2 ; Marisa Russell 1 ; Jeremy P. Nuttall 3 ; NelietteVan Niekerk 1 ; NicolineTreijtel 4 1 International Partnership for Microbicides, Paarl, South Africa; 2 SGS Life Science Services, Antwerp, Belgium; 3 International Partnership for Microbicides, Silver Spring, MD, US; 4 Kinesis Pharma BV, Breda, Netherlands Background: Dapivirine Vaginal Ring-004 (25 mg dapivirine) is a topical microbicide being evaluated for safety and efficacy in a Phase III clinical program. The pharmacokinetic (PK) profile of Ring-004 has been described for up to 35 days of continuous use. This trial investigated the PK of dapivirine from Ring-004 for continuous use up to 12 weeks. Methods: An open-label, parallel group trial was conducted among 40 healthy, HIV-negative women, aged 18-40 years. Participants were divided into 5 groups of 8 women each: participants in Group A kept the ring inserted for 1 week, Group B for 2 weeks, Group C for 4 weeks, Group D for 8 weeks and Group E for 12 weeks. Dapivirine concentrations were determined in plasma and vaginal fluid (CVF) samples collected by tear test strip at the cervix, and residual dapivirine levels were assessed in used rings. Results: Mean plasma dapivirine C max was similar across groups: 385 to 449 pg/mL. Median t max was variable and ranged from 7 days to 17.5 days. Mean C prior to ring removal was similar for rings inserted for 1, 2 or 4 weeks (329 to 379 pg/mL), and showed a pronounced decline for longer ring use: 228 pg/mL at Week 8; 156 pg/mL at Week 12. Maximum dapivirine CVF concentrations were achieved after approximately 1 week, displaying high inter- and intra-individual variability. Mean C max ranged between 48.2 and 61.3 m g/g across groups. Mean C prior to ring removal was similar for rings inserted for 1 or 2 weeks (39.5 and 44.6 m g/g), and then declined with duration of ring use: 20.1 m g/g at Week 4; 17.2 m g/g at Week 8; 13.3 m g/g at Week 12. The lowest concentration observed (Week 12) was 1.1 m g/g, which was well above the in vitro IC 99 in cervical tissue (3.3 ng/mL). Mean ring residual levels of dapivirine were 16.8, 21.6, 20.1, 17.0 and 15.0 mg for Groups A to E. In general, ring residual levels decreased with duration of ring use; results for Groups A and B should be interpreted with caution due to problems with validation of analytical results for these rings. No product-related SAEs occurred. Three AEs of vaginal discharge (Grade 1) and one AE of bacterial vaginitis (Grade 2) were reported as product-related. Conclusions: Dapivirine ring residual levels, and plasma and CVF concentrations decreased with the duration of ring use for periods of greater than 4 weeks; mean CVF concentrations at 12 weeks were >4000 times above IC 99 . Ring-004, when worn continuously up to 12 weeks, was well tolerated with no safety concerns. 525 Steady-state TDF/FTC in Genital, Rectal, and Blood Compartments in Males vs Females Sharon M. Seifert 1 ; Amie L. Meditz 2 ; Jose R. Castillo-Mancilla 3 ; Edward M. Gardner 3 ; Brandon Klein 1 ; Becky Kerr 1 ; L. Anthony Guida 1 ; Jia-Hua Zheng 1 ; Lane R. Bushman 1 ; Peter L. Anderson 1 1 University of Colorado, Aurora, CO, US; 2 Boulder Community Hospital, Boulder, CO, US; 3 University of Colorado School of Medicine, Aurora, CO, US Background: Despite the widespread use of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for treatment and prevention of HIV infection, gaps in knowledge remain regarding the pharmacokinetics (PK) of the intracellular active moieties, tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP), at steady-state concentrations

Poster Abstracts

343

CROI 2015