CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: The fixed drug combination of bictegravir, emtricitabine, tenofovir alafenamide appears to be safe and well-tolerated when used as PEP, with occasional, mainly mild, gastrointestinal side effects, fatigue, and infrequent laboratory abnormalities. This favorable safety profile, and the high completion rates, suggest that BIC/FTC/TAF is a potential option for PEP. 997 HYPO-OSMOLAR RECTAL DOUCHE DELIVERED TFV DISTRIBUTES TFV DIFFERENTLY THAN ORAL PrEP Peng Xiao 1 , Sanjeev Gumber 2 , Mark A.Marzinke 3 , Abhijit Date 3 , Thuy Hoang 3 , Justin Hanes 3 , Laura Ensign 3 , Lin Wang 4 , Lisa C. Rohan 4 , Richard Cone 3 , Edward J. Fuchs 3 , Craig W. Hendrix 3 , Francois Villinger 1 1 University of Louisiana at Lafayette, Lafayette, LA, USA, 2 Emory University, Atlanta, GA, USA, 3 Johns Hopkins University, Baltimore, MD, USA, 4 Magee–Womens Research Institute, Pittsburgh, PA, USA Background: In spite of the PrEP with tenofovir disoproxil fumarate/ emtricitabine (TDF/FTC) rollout, the rate of new HIV infections remains a major hurdle. In the US alone, the rate of new infections has shifted to predominantly men having sex with men in rural settings where access to PrEP can be an issue, in addition to cost and the need for adherence. As an alternative, we have developed an on demand PrEP approach using TFV-based hypo-osmolar (HOsm) rectal douches that are congruent with sexual behavior. Using stringent intrarectal repeated exposures of macaques to SHIV, this approach has delivered significantly better protective efficacy from virus acquisition compared to oral daily TDF and TDF/FTC PrEP. We therefore attempted to delineate the parameters that may dictate such improved efficacy and tested the safety of repeated TFV douching. Methods: Sodium based HOsm intrarectal douches were compared to oral daily PrEP for their ability to promote uptake of TFV into the tissue and circulation. Results: Analysis of HOsm formulation of TFV douche delivery demonstrated the presence of >14,000 fmol/mg TFV-DP at 3 hours 2500 fmol/mg TFV-DP in rectal tissues at 24 h post rectal douching, markedly higher than the ~200 fmol/mg steady state achieved by daily oral PrEP. TFV-DP levels in all other tissues analyzed including colonic lymph nodes draining the rectal mucosa were considerably lower, between 10-30 fmol/mg irrespective of anatomical location. Of note, while single oral TDF and HOsm rectal TDF achieved the same peak of plasma TFV, general AUC were higher for the oral delivered TDF. Rapidly repeated HOsm rectal douching (x5) using 30 vs 60 ml did not cause any detectable tissue or systemic toxicity. The single vs repeated HOsm rectal douching achieved similar TFV and TFV-DP levels in colorectal tissues, but plasma TFV levels were significantly higher for the repeated 60 ml dosing. Gel and bicarbonate formulations of rectal TDF douching did not markedly improve the pharmacokinetics of TFV or TFV-DP in tissues. Conclusion: TFV HOsm douching showed high protection efficacy and appeared well tolerated even after multiple administrations within 30 minutes. The most salient parameter potentially associated with protection from rectal infection appeared to be the considerably higher levels of TFV-DP at the portal of entry but not in distal lymphoid tissues, suggesting that drug levels at that barrier are critical for preventing mucosal virus acquisition. 998 THE POTENTIAL FOR A RECTAL MICROBICIDE DOUCHE: FINDINGS FROM AN INTERNATIONAL SURVEY Rebecca Giguere 1 , Alex Carballo-Dieguez 1 , Cody Lentz 1 , Curtis Dolezal 1 , Edward J. Fuchs 2 , Craig W.Hendrix 2 1 New York State Psychiatric Institute, New York, NY, USA, 2 Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Since many individuals who engage in receptive anal intercourse (RAI) regularly use cleansing rectal douches beforehand, an HIV-prevention douche could have high acceptability. Administration of tenofovir via a rectal douche results in faster and higher drug concentration in the rectal mucosa than oral administration. We aimed to describe behavioral aspects of rectal douching before RAI in different international settings to inform development of a behaviorally congruent tenofovir douche. Methods: Using the social media app Grindr, we recruited individuals aged 18 or above, born male, who had engaged in RAI in the past three months. They completed an online survey about their rectal douching practices. The survey was available in English, Spanish, and French. Participants were recruited from: 1) the United States and its territories; 2) Latin America; 3) Africa. Data were analyzed using descriptive statistics.

Results: In total, 5,127 participants from 52 countries responded; 87% from the US, 10% from Latin America, and 3% from Africa. Among those who reported RAI, 80% in the US, 63% in Latin America, and 73% in Africa reported douching beforehand. Proportions who reported douching after RAI included 27% in the US, 37% in Latin America, and 59% in Africa. Most (90%) douched for cleanliness, though one-quarter of respondents in Latin America and Africa believed it might prevent infections. While half of US respondents used an enema bottle, reported use of this device was less common in other regions, with infrequent use in Africa (14%). Instead, a hose attached to a faucet was most popular in Latin America (51%) and Africa (45%), while a rubber bulb was used across all regions (39%). Tap water was the liquid preferred by 89% of respondents in all regions. Among those who did not douche, most had never thought about it (58%) or did not feel the need (28%). Finally, 98% of those who douched and 96% those who did not reported likelihood of using a rectal douche to prevent HIV transmission. Conclusion: Findings from this international survey demonstrate a high prevalence of rectal douching associated with RAI and high likelihood of using a rectal microbicide douche to prevent HIV if one were available, even among those who do not currently douche. Ideally, an HIV-prevention douche should be adaptable to various devices, as enema bottles such as those used for douche administration in current clinical trials are not commonly used in regions outside of the US.

Poster Abstracts

999 A PHASE I TRIAL OF A RECTALLY ADMINISTERED GEL FORMULATED WITH THE NNRTI IQP-0528 Amer Al-Khouja 1 , Eugenie C. Shieh 1 , Edward J. Fuchs 1 , Mark A.Marzinke 1 , Anthony S. Ham 2 , Karen W. Buckheit 2 , Jennifer Breakey 1 , Ethel D. Weld 1 , Robert W. Buckheit 2 , Craig W. Hendrix 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 ImQuest BioSciences, Inc, Frederick, MD, USA Background: There is an unmet need for the development of a dual-purpose topical microbicide, for rectal and vaginal use, as pre-exposure prophylaxis (PrEP) against HIV. A microbicide gel was formulated with IQP-0528, a potent non-nucleoside reverse transcriptase inhibitor (NNRTI). The primary objectives of this study were to assess local and systemic safety, and to evaluate single- dose pharmacokinetics (PK) and pharmacodynamics (PD) in plasma, and rectal and cervicovaginal (CV) tissue following rectal dosing of an IQP-0528 gel. Methods: In this phase 1, open-label trial, 7 healthy participants (4 men and 3 women) received a 10 mL rectal dose of 1% IQP-0528 gel. Plasma sample collection was adaptively designed, with samples initially collected over 72 h (4 participants), and then over 48 h (3 participants). Rectal tissue (RT) biopsies were collected at baseline (5), 3-6 h post-dose (14), and 24-26 h post-dose (14). CV biopsies were collected at baseline (2), and 24-26 h post-dose (4). Biopsies were distributed for measurements of IQP-0528 concentration, and ex vivo HIV challenge assays. Results: 4 adverse events (AEs) were experienced in 3 participants. None was Grade 3 or higher and 1 Grade 1 event was attributed to study product. All concentrations measured from plasma and CV tissue were below the limit of quantitation, indicating a lack of systemic exposure with no transfer to CV

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