CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

may have sub-clinical intolerance. These patients may therefore gain more weight after switch from EFV-based ART to INI-based ART.

474 BICTEGRAVIR CONCENTRATIONS AND VIRAL SUPPRESSION IN CSF HIV– INFECTED PATIENTS Juan M. Tiraboschi 1 , Arkaitz Imaz 1 , Saye Khoo 2 , Jordi Niubo 1 , Paula Prieto 1 , Maria Saumoy 1 , Sujan Dilly Penchala 2 , Benito Garcia 1 , Cristina Padilla 1 , Daniel Podzamczer 1 1 Bellvitge University Hospital, Barcelona, Spain, 2 University of Liverpool, Liverpool, UK Background: Bictegravir (BIC) is a novel, potent, once-daily, unboosted inhibitor of HIV-1 integrase specifically targets IN strand transfer activity. BIC differs from previously known structures in that it contains a unique bridged bicyclic ring and a distinct benzyl tail consisting of a tri substituted 2,4,6-trifluorobenzyl moiety. These changes resulted in increased plasma protein binding to improve its solubility. These two physicochemical characteristics are crucial determinants of drug penetration. The aim of our study was to determine BIC levels in cerebrospinal fluid (CSF) as well as HIV viral load in this compartment. Methods: This is a single-arm, open-label, single-center study. After an initial assessment, 15 participants switched from stable ART to FTC/TAF/BIC (Biktarvy®). At week 4, plasma and CSF concentrations of BIC were measured 24 hs post-dose, using a validated LC-MS methodology (assay calibration range is 10-10,000 ng/ml for plasma and 1-100 ng/ml for CSF). HIV RNA was measured in plasma and CSF by RT-PCR ( LLQ 40 copies/mL). Results: A total of 15 plasma an 15 CSF samples were collected. At baseline, median CD4 count was 776 cells/uL (613 – 905). Most patients switched from Genvoya® and Triumeq® (57,2%). One patient presented with unexpected low BIC concentrations in plasma and CSF while concomitantly taking self- prescribed magnesium supplements*. Conclusion: Although the target concentrations are unknown, total trough BIC concentrations in CSF were near or just above the in vitro 50% inhibitory concentration for wild-type HIV (IC50: 3.54 ng/mL), suggesting that BIC given in combination with FTC/TAF may contribute to inhibit viral replication in this compartment.

473 HORMONAL CONTRACEPTIVES DO NOT ALTER CABOTEGRAVIR PK IN HIV- UNINFECTED WOMEN HPTN 077 Cherie Blair 1 , Sue Li 2 , Gordon Chau 3 , Leslie Cottle 3 , Paul Richardson 4 , Mark A. Marzinke 4 , Susan H. Eshleman 4 , Adeola Adeyeye 5 , David Burns 6 , Alex Rinehart 7 , David A. Margolis 7 , Marybeth McCauley 8 , Craig W. Hendrix 4 , Raphael J. Landovitz 1 , for the HPTN 077 Study Team 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA, 3 Statistical Center for HIV/ AIDS Research and Prevention, Seattle, WA, USA, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 NIH, Rockville, MD, USA, 6 NIH, Bethesda, MD, USA, 7 ViiV Healthcare, Research Triangle Park, NC, USA, 8 FHI 360, Washington, DC, USA Background: Long-acting Injectable Cabotegravir (CAB LA) is a novel strand- transfer integrase inhibitor, currently in development for HIV prevention and treatment. Unexpected drug-drug interactions (DDI) between ARVs and hormones for contraception or cross-sex therapy have been noted for other ARVs, ranging from 13% to 38% reduction in tenofovir exposure (AUC) in the setting of estrogen with or without anti-androgen use. Understanding such DDIs is critical to acceptability and scale up of novel treatment and prevention paradigms. Methods: We performed a secondary analysis of cisgender women who were enrolled in HPTN 077, a Phase 2a multicenter study that enrolled HIV- uninfected, low risk individuals in Malawi, Brazil, South Africa, and the US. Participants received a 4 week oral CAB lead-in, followed by CAB LA 800mg Q12w IM (Cohort 1) or 600mg q8w IM (after a 4 week initial interval between injections, Cohort 2) over 41 weeks. Participants were followed 52-76 weeks subsequent to their final injection. Linear regression was used to evaluate differences in pharmacokinetic (PK) parameters (peak concentration [Cmax], trough [Cτ], exposure after the last injection [AUC0-τ], and apparent terminal half-life after the last injection [T1/2app]) between hormonal contraception (use vs not) and contraception type (oral, injectable, vaginal ring, implants, other) controlling for body mass index (BMI) and CAB dose cohort. Results: 85 cisgender females enrolled in HPTN 077 and received at least 1 dose of active CAB LA. In this study population, BMI associated with 1% reduction (per unit increase in BMI) in Cmax, Cτ, and AUC0-τ and 2% increase in T1/2app. Median BMI was 27.2 in Cohort 1 and 25.7 in Cohort 2. Use of any type of hormonal contraceptive, individually or in aggregate, did not result in statistically significant changes in Cmax, Cτ, AUC0-τ, or T1/2app (Table, all p >0.05, Cmax, AUC0-τ not shown). No pregnancies occurred among those receiving active CAB LA during the study period. We did not assess the impact of CAB on estrogen concentrations. Conclusion: Among HIV-uninfected females in HPTN 077, use of hormonal contraception did not alter the CAB concentration profile during injections or during the pharmacokinetic tail. While there is no anticipation of an effect of CAB on estrogen concentration, the effects of CAB LA on hormonal treatment for both contraception and gender-affirming treatment warrant evaluation.

Poster Abstracts

CROI 2019 175