Multipurpose vaginal rings for HIV prevention and treatment of bacterial vaginosis

This thesis is focused on the developvent of a multipurpose prevention technology (MPT) vaginal ring that can provide sustained release of two or more of the following actives: dapivirine (DPV, a potent experimental antiretroviral); metronidazole (MET, 5-nitroimidazole antibiotic drug); sucrose (selectively promotes the growth of lactobacilli), and boric acid (antimicrobial and antibiofilm properties) to prevent HIV infection and, at the same time, treat or prevent BV. A matrixtype silicone elastomer vaginal ring developed by the International Partnership for Microbicides (IPM) and providing 28-day continuous release of DPV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), was prequalified by the WHO in 2020 and received a recommendation in WHO’s HIV guideline in 2021. The development of next-generation vaginal rings is primarily focused on so-called ‘multipurpose prevention technology’(MPT) products which aim to simultaneously prevent HIV-1 infection, unintended pregnancy and other sexually transmitted infections using a single product. Bacterial vaginosis is a common lower genital tract disorder in reproductive age women and is characterized by the replacement of a Lactobacillus-dominated microbiota by a variable mixture of anaerobic and facultative bacteria. It has been reported that bacterial vaginosis is associated with an increased risk of HIV acquisition. The experimental results obtained to date are encouraging and support the continued development of these ring formulations as a novel and interesting MPT strategy. A study exploring women’s preferences around design characteristics (colour, scent and size) of drug-releasing vaginal rings in the collaboration with Cecilia Milford from University of the Witwatersrand was conducted in 2021. Opinions varied on ring colour and scent, with some women preferring specific colours or scent intensities, while for others these attributes were unimportant