Antiretroviral Landscape: Assessment to Identify Potential Alternative Candidates for Antiretroviral Pre-exposure Prophylaxis Microarray Patch

Microarray patches (MAPs) are a promising delivery technology that could improve adherence to HIV PrEP by providing long-acting (LA) protection against HIV. MAP technology has the potential to enable self-administration and improve thermostability, but it must overcome regulatory and manufacturing barriers to become a viable commercial product with public health impact. The primary objective of this landscape analysis is to survey antiretroviral (ARV) drugs that are currently available and in development for HIV PrEP and to prioritize ARVs most suitable for delivery with a MAP. The analysis identified 10 ARVs from existing classes that have been approved by stringent regulatory authorities for HIV treatment or PrEP, 12 investigational ARVs from existing classes, and 2 new compounds from a new class. Four candidates were selected for an in-depth analysis for MAP formulation potential, including pharmacokinetic and pharmacokinetic considerations. Integrase inhibitors, which prevent incorporation of viral HIV DNA into host-cell DNA, are the most favorable class of ARVs for PrEP candidates. Among the HIV PrEP candidates surveyed, cabotegravir (CAB) is the most viable candidate for formulation into the MAP delivery system. CAB has a long half-life, low effective dose, high barrier to resistance, high protein-binding affinity, low water solubility, and low plasma clearance, making it a promising candidate for MAP formulation and delivery. If PATH is unable to finalize an agreement with GlaxoSmithKline (GSK) and ViiV Healthcare for access to CAB for ARV MAP development, PATH will consult with the United States Agency for International Development (USAID) and members of the Project Advisory Committee on next steps. This may involve reaching out to Merck & Co. and Gilead Sciences, Inc. to explore their willingness to provide access to raltegravir (RAL) or elvitegravir (EVG), respectively, for project activities. Ultimately, a MAP formulation for delivery of a LA ARV must provide efficacy equivalent to or better than current HIV PrEP formulations to become a viable option for HIV prevention. The development of a MAP formulation for CAB or other ARVs will require careful consideration of the molecular properties of the ARV, as well as the required excipients, to ensure that the formulation can be delivered from the dissolving MAP delivery platform. The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that there were 2.1 million new HIV infections worldwide in 2015, with adolescent girls and young women accounting for 20% of new infections among adults globally. In sub-Saharan Africa, adolescent girls and young women accounted for 25% of new infections among adults. These disparities highlight the need for effective HIV prevention strategies, including PrEP, to protect vulnerable populations. The development of a MAP formulation for HIV PrEP has the potential to improve adherence and reduce the risk of HIV transmission. However, it is essential to carefully consider the molecular properties of the ARV and the required excipients to ensure that the formulation can be delivered from the dissolving MAP delivery platform.