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High resolution and 3D ultrasound imaging of implant and intravaginal ring drug delivery devices during HIV pre-exposure prophylaxis (PrEP) preclinical and clinical studies
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Presented at the HIVR4P, Virtual, 27-28 January and 3-4 February 2021
Presenter
Kathleen Listiak Vincent
Authors
J.A. Moss (1), Y. Zhu (2), G. Va
rgas (2), R.B. Pyles (2), M.M. Baum (1), M. Motamedi (2), K.L. Vincent * (2)
Institutions
(1) Oak Crest Institute of Science, Monrovia, United States, (2) University of Texas Medical Branch, Galveston, United States
BACKGROUND: Clinical trials support the use of daily HIV pre-exposure prophylaxis (PrEP), however compliance with frequent dosing schedules as well as plasma fluctuations can be limitations. Longer acting formulations can address these limitations by providing long-term steady state drug release through devices such as subdermal implants and intravaginal rings (IVRs). Clinically, ultrasound (US) imaging has been used to locate nonpalpable contraceptive implants while 3D reconstruction has been utilized for vaginal foreign body (mesh) localization. These techniques can be applied to evaluate drug-delivery devices designed to release PrEP. The goal of these studies is to utilize ultrasound imaging for anatomic mapping and observation of HIV PrEP-releasing devices during preclinical and clinical studies.
METHODS: PrEP-releasing silicone subdermal implants were evaluated in sheep (n=4) with a high-resolution US system, Visualsonics Vevo 2100 (22-55MHz linear probe). Images were obtained at the implant insertion site for assessment of implant location and tissue irritation, including edema (interstitial fluid, increased echogenicity), and hypervascularity (increased flow by Doppler). In the clinical study, a GE Voluson 730PRO US system (convex 2-5MHz, endocavitary 4-9MHz probes) was utilized for 2D/3D imaging of vaginal rings in women (n=10) using placebo or PrEP drug-releasing IVRs in a 28-day crossover study. Image volume sets were obtained and reconstructed to produce views of the IVR in relation to the uterus, cervix, bladder, and pubic symphysis.
RESULTS: Subcutaneous implants were visualized best in the transverse plane, similar to human contraceptive implants. The implants were linear and located 2-4mm deep. One implant was visualized within the muscle layer, a finding not detectable by palpation. No signs of tissue irritation were present. In the clinical study, IVRs, visible via abdominal and trans-perineal scanning, were hypoechoic, while the pods containing drug or placebo were hyperechoic. The IVRs were non-compressed, located in the posterior fornix extending to the level of the mid bladder, with the distal IVR edge located 2.3-3.5 cm from the pubic symphysis.
CONCLUSIONS: US imaging can enhance preclinical and clinical PrEP studies, providing vital information about device placement, location, and deformity in situ. It also has potential to detect signs of toxicity during use of subdermal implants.
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