Globally, over 50% of those infected with HIV are women, and annually, ~50% of all pregnancies are unintended. Therefore, there is a critical need to promote female-controlled methods of multipurpose prevention and delivery strategies that can be disassociated from the sex act. Intravaginal rings are well tolerated by women, are efficacious for contraception and hormone replacement therapy, and have high patient compliance [1-4]. However, developing effective multipurpose IVRs is challenging due to the complexity of current engineering processes [5, 6], and differences in drug properties and release rates, thus mandating drug-specific customized IVR designs. The ultimate goal of this proposal is to address these limitations by revolutionizing the engineering process of intravaginal rings using a state-of-the-art 3D printing process known as the continuous liquid interface production (CLIP?) [7]. Using CLIP, we can engineer IVRs with complex geometries that cannot be achieved with traditional injection molding or extrusion. The complex geometries within the ring will allow us to precisely fine-tune diffusion and release of drugs from the IVR, and achieve near complete release of drugs from the IVR. More importantly, with CLIP, we can manufacture multipurpose IVRs that can integrate 2 or more drugs to prevent against unintended pregnancies and STIs (HIV, HSV-2, HPV) in a rapid and cost effective single-step process. We propose a comprehensive evaluation of this innovative approach using a highly relevant macaque model of mucosal simian/human immunodeficiency virus (SHIV162p3) as an invaluable preclinical tool to assess the efficacy of the IVRs against SHIV acquisition [8- 10]. This cutting edge combined approach will be utilized to evaluate the scientific premise of our proposal to investigate whether sustained protection against HIV acquisition can be achieved along with sustained delivery of a contraceptive drug using a unique and highly innovative 3D printed multipurpose IVR.
The benefit of multipurpose prophylaxis to women with high risk of HIV/STIs infection is significant. Long-acting intravaginal formulations providing steady release over weeks or months of antiretroviral drugs in combination with a contraceptive drug can potentially increase compliance to STIs and unintended pregnancy prophylactic regimen and transform the HIV prevention landscape. The overarching goal of this proposal is to develop and evaluate an innovative approach to multipurpose intravaginal rings that can contribute to curb the HIV epidemic.
