CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

tissue following rectal dosing. The median [IQR] IQP-0528 concentration in RT 3-6 h and 24-26 h post-dose was 4914 [2907, 5142] ng/mg and 5.4 [3.5, 7.5] ng/mg, respectively, with a median [IQR] half-life of 2.24 [2.23, 2.32] h. In RT, the median [IQR] cumulative p24 3-6 h post-dose (0.1 [0.0, 0.3] pg/mg) was reduced relative to that at baseline (38.4 [22.0, 63.7] pg/mg; p = 0.0277), and 24-26 h post-dose (53.1 [6.6, 144.8] pg/mg; p = 0.0350). The median [IQR] IC 50 determined was 47.4 [3.4, 183.0] ng/mg. In CV biopsy explants, p24 was not significantly different at baseline versus 24-26 h post-dose (p = 1.0000). Conclusion: The IQP-0528 gel was found to be safe and well tolerated. Despite the short IQP-0528 half-life in RT, concentrations remained well above the in vitro IC 90 of 146 ng/mL within 3-6 h post-dosing. RT PD indicated that cumulative p24 reductions are significantly associated with greater IQP-0528 (Fig. 1). The offset of IQP-0528 accumulation by its short half-life in RT indicates that this gel may be better suited for episodic use. Furthermore, dual protection is not offered from single-compartment dosing.

studies to correlate in-vitro and in-vivo results. This MPT platform offers the potential to address the unmet need for dual protection against unintended pregnancy and HIV infection in resource-limited areas.

1001 WITHDRAWN 1002 HIV-1 DRUG RESISTANCE IN THE DISCOVER PREEXPOSURE PROPHYLAXIS TRIAL Stephanie W. Cox 1 , Urvi Parikh 2 , Amy Heaps 2 , Breanna J. Goetz 2 , John W. Mellors 2 , Xinan Liu 1 , Ross Martin 1 , Jenny Svarovskaia 1 , Hadas Dvory-Sobol 1 , Scott McCallister 1 , Christian Callebaut 1 1 Gilead Sciences, Inc, Foster City, CA, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA Background: The DISCOVER study is an ongoing randomized, double blind study of pre-exposure prophylaxis (PrEP) using daily FTC/TAF (F/TAF; Descovy; DVY) or FTC/TDF (F/TDF; Truvada; TVD) in men or transgender women who have sex with men. Of the 5,335 randomized participants, 23 participants (0.4%) became infected with HIV-1 through 96 weeks on study. The infected participants from the DISCOVER study were evaluated with both standard and ultrasensitive sequencing and the overall resistance data and analysis are presented here. Methods: Plasma samples from participants who became HIV-1 infected and had a viral load of > 400 copies/mL were tested with the Monogram GenoSure™ MG assay, using Sanger sequencing to analyze the protease (PR) and reverse transcriptase (RT) genes for any known resistance mutations (at ≥20% of the viral population). Identification of minor variants was evaluated using ultrasensitive resistance testing (at ≥1% of the viral population) on all available plasma samples using unique molecular identifiers with next generation sequencing (UMI-NGS) to analyze RT codons 63-131 and 152-211 (University of Pittsburgh). Results: By standard sequencing, 4/20 HIV positive participants tested had M184V, all in the F/TDF group and all with suspected baseline infection; 2 of these 4 also had M184I present. Six participants had additional mutations conferring resistance to non-study drugs including NRTI, NNRTI, and PI, which were presumed to be transmitted. By UMI-NGS, 22/23 HIV infected participants had samples available and 20/22 were successfully analyzed. The four participants with M184V each had M184I also detected; K65R was detected in 1 participant at very low levels. One participant on F/TAF had the M184V mutation present at 2%. Two out of 3 participants with samples that had viral loads < 400 copies/mL were successfully tested and neither had resistance to study drugs. Conclusion: Using standard sequencing, M184V was detected in 4 participants, all in the F/TDF arm. Using ultrasensitive UMI-NGS testing, similar results were observed, with the addition of one participant with M184V in the F/TAF arm and one participant with possible low level K65R in the F/TDF arm. Overall, drug resistance in the DISCOVER study was most commonly seen in participants with suspected baseline infections and in only 1 individual who became infected while on study. 1003 PrEP SEROCONVERSION-SEGMENTAL HAIR ANALYSIS FOR UNRAVELING TIMING OF VIRAL RESISTANCE Brentton T. Lowery 1 , Hideaki Okochi 2 , Karen Kuncze 2 , Nhi Phung 2 , Cheryl McDonald 3 , Matthew A.Spinelli 2 , Anthony Mills 1 , Patricia A.Defechereux 2 , Kathryn Jee 2 , Peter L.Anderson 4 , Robert M. Grant 2 , Monica Gandhi 2

Poster Abstracts

1000 BIODEGRADABLE IMPLANT FOR DELIVERY OF ANTIRETROVIRAL (ARV) AND HORMONAL CONTRACEPTIVE Linying A. Li 1 , Sai Archana Krovi 1 , Chasity Norton 1 , Ellen Luecke 2 , Zach Demkovich 1 , Pafio Johnson 1 , Christine Areson 1 , Guadalupe Jimenez 1 , Ariane Van Der Straten 2 , Leah M.Johnson 1 1 RTI International, Research Triangle Park, NC, USA, 2 RTI International, San Francisco, CA, USA Background: Women worldwide confront two frequently concurrent reproductive health challenges: the need for contraception and protection from sexually transmitted infections, including HIV. Multipurpose prevention technologies (MPTs) that simultaneously prevent unintended pregnancy and HIV could address these challenges with one product. Here, we are developing a long-acting (LA) subcutaneously administered and biodegradable implant system that provides sustained delivery of hormone and antiretroviral (ARV) with zero-order release kinetics. Methods: Polycaprolactone (PCL) tubes were extruded and filled with various formulations and enclosed by heat sealing. In-vitro release from devices (in PBS, pH 7.4 at 37˚C) was monitored over 7 months using UV-vis spectroscopy or HPLC. Devices were transferred to fresh buffer three times per week to maintain sink conditions. Results: We selected two well-characterized progestins, levonorgestrel (LNG) and etonogestrel (ENG), as well as one ARV, tenofovir alafenamide (TAF), for MPT indication. We formulated these active pharmaceutical ingredients (APIs) with several excipients and identified the lead excipients that support the targeted release kinetics, requisite dosing and long-term stability of the APIs. We achieved sustained delivery of LNG, ENG and TAF with zero-order release kinetics for 7 months (Figure 1) and high stability of APIs. Devices with LNG formulation demonstrated linear release kinetics at approximately 30 mg/day, and LNG inside the device core displayed >98% stability after 7 months of in-vitro release. ENG formulations exhibited zero-order release kinetics at approximately 35 mg/day and maintained a purity of >99% after 7 months in-vitro. We also demonstrated sustained release of TAF at 180 mg/day with a purity of >93% at the 6-month timepoint. This MPT system is amenable to administration of two implants in-line with a single trocar or as a single segmented implant that houses different drug formulations in each compartment. Conclusion: We developed a LA MPT implant system for sustained delivery of TAF, LNG and ENG with zero-order kinetics that maintains in-vitro stability of the APIs. We are currently evaluating this implant system in preclinical animal

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