PATH_MAPs for PrEP_annual performance report_31July2018

The primary objective is to develop a dissolving MAP for delivery of an ARV for long-acting HIV PrEP to the point of Phase 1 clinical readiness. To achieve this objective, the project is divided into two specific aims. Aim 1 focuses on developing a dissolving MAP for delivery of an ARV for long-acting HIV PrEP. This aim is further divided into four activities: establishing an agreement with a pharmaceutical company to obtain an ARV, advancing preclinical development of an ARV MAP, evaluating the acceptability of an ARV MAP for HIV prevention and a multipurpose prevention technology (MPT) MAP for HIV prevention and contraception, and establishing the product development pathway for ARV MAPs. Under Activity 1.1, an agreement was signed with ViiV Healthcare (ViiV) for access to cabotegravir (CAB) to develop the analytical method and the long-acting nanoparticle formulation of cabotegravir (CAB LA) for MAP formulation development. This was completed on December 12, 2017. Under Activity 1.2, Queen's University Belfast (QUB) validated analytical methods to quantify CAB LA, optimized MAP formulations, completed in vitro physiochemical characterization, completed preliminary in vivo dose-range finding experiments in rats, and initiated a stability study. Under Activity 1.3, LVCT Health (Kenya), Genesis Analytics (South Africa), and the Child Health and Development Centre (CHDC) at the Makerere University College of Health Sciences (Uganda), with PATH's support, developed in-country usability and acceptability evaluation protocols and data collection tools for submission to local ethics review boards. PATH also developed and fabricated three iterations of MAP feedback indicator prototypes, drafted prototype packaging designs and instructions for use, and conducted a human factors evaluation. Under Activity 1.4, the Population Council (PC) drafted a preliminary clinical/regulatory plan in collaboration with and with input from PATH, QUB, LTS Lohmann Therapie-Systeme AG (LTS), and ViiV. The clinical/regulatory plan will evolve throughout the project and will be updated as new data are generated. Aim 2 focuses on exploring the potential of a segmented dissolving MPT MAP for delivery of both an ARV for long-acting HIV PrEP and a hormonal contraceptive for pregnancy prevention. This aim is further divided into one activity: advancing proof-of-concept development of a contraceptive MAP to enable an MPT MAP. Under Activity 2.1, QUB initiated formulation development activities for a future MPT MAP by validating analytical methods to quantify norelgestromin and creating long-acting nanoparticles for slow release of the drug. The project holds regular technical calls and meetings with partners to review data, align project milestones and activities, and coordinate next steps. These calls include monthly technical calls with QUB, PC, LTS, ViiV, and GlaxoSmithKline (GSK), individual biweekly partner calls with QUB and PC, and a monthly call with LTS. The project also holds individual biweekly calls with LVCT Health, Genesis Analytics, and CHDC, as well as a monthly call with all country partners included. The project has made significant progress in advancing the development of the MAP technology for delivery of an ARV for long-acting HIV PrEP. The next steps will focus on completing the preclinical development of the ARV MAP, evaluating its acceptability, and establishing the product development pathway for ARV MAPs.