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: Introduction: Emerging long‐acting (LA) prevention and treatment medicines, technologies and regimens could be game‐changing for the HIV response, helping reach the ambitious goal of halting the epidemic by 2030. To attain this goal, the rapid expansion of at‐scale, sustainable, quality‐assured, and affordable supplies of LA HIV prevention and treatment products through accelerated and stronger competition, involving both originator and generic companies, will be essential. To do this, global health stakeholders should take advantage of voluntary licensing of intellectual property (IP) rights, such as through the United Nations‐backed, not‐for‐profit Medicines Patent Pool, as a proven mechanism to support broad access to existing HIV medicines across low‐ and middle‐income countries (LMICs). Discussion: While voluntary licensing may unlock the possibility for generic competition to take place ahead of patent expiry, there are additional elements—of amplified importance for more complex LA HIV medicines—that need to be taken into consideration. This paper discusses 10 enablers of voluntary licensing of IP rights as a model to rapidly expand at‐scale, sustainable, quality‐assured, and affordable supplies of LA HIV prevention and treatment regimens in LMICs: 1. Identifying promising LA technology platforms and drug formulations at an early developmental stage and engaging with patent holders 2. Consolidating a multidisciplinary network and strengthening early‐stage coordination and collaboration to foster innovation 3. Embedding public health considerations in product design and delivery 4. Building innovative partnerships for product development and commercialization 5. Raising awareness of and creating demand for emerging LA products 6. Estimating the market size, ensuring sufficient competition and protecting sustainability 7. Using technology transfer and hands‐on technical support to reduce product development timelines and costs 8. Exploring de‐risking mechanisms and financial incentives to support generic manufacturers 9. Optimizing strategies for generic product development and regulatory filings 10. Aligning and coordinating efforts of stakeholders across the value chain. Conclusions: Rapid access to emerging LA prevention and treatment regimens and technologies can be facilitated by voluntary licensing—catalyzed and supplemented by enabling collaborative and non‐duplicative efforts of various other stakeholders. This can effectively lead to improved—accelerated and cheaper—access to quality‐assured medicines for populations in LMICs., INTRODUCTION Emerging long‐acting (LA) prevention and treatment medicines, technologies and regimens could be game‐changing for the HIV response [1–6]. The rapid expansion of at‐scale, sustainable, quality‐assured, and affordable supplies of [...]

: Introduction: Worldwide, 71 million people are infected with hepatitis C virus (HCV), which, without treatment, can lead to liver failure or hepatocellular carcinoma. HCV co‐infection increases liver‐ and AIDS‐related morbidity and mortality among HIV‐positive people, despite ART. A 12‐week course of HCV direct‐acting antivirals (DAAs) usually cures HCV – regardless of HIV status. However, patents and high prices have created access barriers for people living with HCV, especially people who inject drugs (PWID). Inadequate access to and coverage of harm reduction interventions feed the co‐epidemics of HIV and HCV; as a result, the highest prevalence of HCV is found among PWID, who face additional obstacles to treatment (including stigma, discrimination and other structural barriers). The HIV epidemic occurred during globalization of intellectual property rights, and highlighted the relationship between patents and the high prices that prevent access to medicines. Indian generic manufacturers produced affordable generic HIV treatment, enabling global scale‐up. Unlike HIV, donors have yet to step forward to fund HCV programmes, although DAAs can be mass‐produced at a low and sustainable cost. Unfortunately, although voluntary licensing agreements between originators and generic manufacturers enable low‐income (and some lower‐middle income countries) to buy generic versions of HIV and HCV medicines, most middle‐income countries with large burdens of HCV infection and HIV/HCV co‐infection are excluded from these agreements. Our commentary presents tactics from the HIV experience that treatment advocates can use to expand access to DAAs. Discussion: A number of practical actions can help increase access to DAAs, including new research and development (R&D) paradigms; compassionate use, named‐patient and early access programmes; use of TRIPS flexibilities such as compulsory licences and patent oppositions; and parallel importation via buyers’ clubs. Together, these approaches can increase access to antiviral therapy for people living with HIV and viral hepatitis in low‐, middle‐ and high‐income settings. Conclusions: The HIV example provides helpful parallels for addressing challenges to expanding access to HCV DAAs. HCV treatment access – and harm reduction – should be massively scaled‐up to meet the needs of PWID, and efforts should be made to tackle stigma and discrimination, and stop criminalization of drug use and possession., Introduction Worldwide, an estimated 71 million people have chronic hepatitis C virus (HCV) infection; 2.3 million of them are HIV co‐infected. The highest prevalence of HCV infection – 82% – [...]

: Introduction: Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. Discussion: The Global Accelerator for Paediatric Formulations (GAP‐f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low‐ and middle‐income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP‐f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP‐f will reinforce coordinated procurement and communication with suppliers. The GAP‐f will be implemented in a three‐stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. Conclusions: GAP‐f is a key partnership example enhancing North‐South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity‐building). By promoting access to the most needed paediatric formulations for HIV and high‐burden infectious diseases in low‐and middle‐income countries, GAP‐f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super‐fast‐track targets., Introduction Prompt treatment of people living with HIV (PLHIV) with appropriate antiretroviral drugs (ARVs) saves lives and improves health, but the 43% ARV treatment (ART) coverage of children living with [...]

Abstract Background Pre-elafin/trappin-2 is a human innate defense molecule initially described as a potent inhibitor of neutrophil elastase. The full-length protein as well as the N-terminal "cementoin" and C-terminal "elafin" domains were also shown to possess broad antimicrobial activity, namely against the opportunistic pathogen P. aeruginosa. The mode of action of these peptides has, however, yet to be fully elucidated. Both domains of pre-elafin/trappin-2 are polycationic, but only the structure of the elafin domain is currently known. The aim of the present study was to determine the secondary structures of the cementoin domain and to characterize the antibacterial properties of these peptides against P. aeruginosa. Results We show here that the cementoin domain adopts an α-helical conformation both by circular dichroism and nuclear magnetic resonance analyses in the presence of membrane mimetics, a characteristic shared with a large number of linear polycationic antimicrobial peptides. However, pre-elafin/trappin-2 and its domains display only weak lytic properties, as assessed by scanning electron micrography, outer and inner membrane depolarization studies with P. aeruginosa and leakage of liposome-entrapped calcein. Confocal microscopy of fluorescein-labeled pre-elafin/trappin-2 suggests that this protein possesses the ability to translocate across membranes. This correlates with the finding that pre-elafin/trappin-2 and elafin bind to DNA in vitro and attenuate the expression of some P. aeruginosa virulence factors, namely the biofilm formation and the secretion of pyoverdine. Conclusions The N-terminal cementoin domain adopts α-helical secondary structures in a membrane mimetic environment, which is common in antimicrobial peptides. However, unlike numerous linear polycationic antimicrobial peptides, membrane disruption does not appear to be the main function of either cementoin, elafin or full-length pre-elafin/trappin-2 against P. aeruginosa. Our results rather suggest that pre-elafin/trappin-2 and elafin, but not cementoin, possess the ability to modulate the expression of some P.aeruginosa virulence factors, possibly through acting on intracellular targets.