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Introduction: Antiretroviral-based pre-exposure prophylaxis (PrEP) is today an established, effective and safe method of HIV prevention used in multiple countries worldwide by a broad range of populations at risk of HIV infection. Biomedicalinno-vations are criticalin supporting the primary prevention of HIV; however, their potentialcan only be maximized if end-user challenges are recognized, described and used to develop next-generation models. Discussion: First-generation PrEP, a daily oralpill, is highly efficacious, discreet and affords users the ability to commence and conclude treatment rapidly. However, consistent daily adherence and persistence is challenging, especially among younger populations, due in part to side effects, the risk of stock-outs and a lack of pillstorage options. Second-generation PrEP, longer acting agents that require less frequent dosing, could overcome such challenges. Agents that have shown efficacy in clinical trials include a monthly vaginalring and PrEP injectables to be administered every 8 weeks, while products in development include 6 monthly injectables, oral therapy that uses monthly rather than daily pills, implants and the potentialfor long-acting passive immunization. Conclusions: Second-generation PrEP agents will have the potential to offer improved adherence and less frequent reminders once they have undergone further development and the delivery systems that will best support them have been established. In order to pursue globalUNAIDS targets of reducing new HIV infections to fewer than 500,000 annually by 2025, and to ensure that allpeople have access to prevention options that meet their specific prevention needs, both early and next-generation PrEP options are needed. Keywords: pre-exposure prophylaxis; long-acting PrEP; HIV prevention; oral PrEP; injectable PrEP; PrEP implants, 1 | INTRODUCTION We have known for more than a decade that antiretroviral-based pre-exposure prophylaxis (PrEP) provides robust protection against HIV infection in all populations and through allroutes of infection [...]

Our perspective and experience of HIV is fundamentally shaped by our age. HIV emerged in 1981 and we, the millennials and all subsequent generations, were brought up in a world [...]

The number of products that can provide pre-exposure prophylaxis (PrEP) for HIV prevention is expanding, with three now approved in South Africa (oral Tenofovir-based PrEP, injectable Cabotegravir, and a Dapivirine-based vaginal ring) and more in the development pipeline. Although highly effective and safe, oral PrEP products have not reduced HIV incidence in South Africa to the extent seen in other countries, primarily due to adherence challenges, rapidly diminishing persistence over time, and insufficient scale-up of PrEP service delivery. The Dapivirine vaginal ring, which provides 1-month-long protection, provides women with a new and discreet choice for PrEP; however, it is Cabotegravir long-acting (CAB LA) that is anticipated to land the largest impact. Administered as an intramuscular injection given every 2 months, CAB LA is safe, highly efficacious, and expected to become available in South Africa in late 2023. Yet, clinical and implementation questions remain, including the need to understand and characterise breakthrough HIV infections amongst CAB LA users, knowledge of how to package each PrEP product in a new context of PrEP choice, and how to avoid the remedicalisation of PrEP access following extensive efforts to make oral PrEP delivery differentiated and community based. [ABSTRACT FROM AUTHOR]

The authors comment on a study published within the issue which reviewed preexposure prophylaxis (PrEP) and examined the opportunities presented to providers in offering oral PrEP to their adolescent clients. Topics covered include ways on how oral PrEP can be introduced to prevent the risk and danger associated with sexual activity, and the opportunities presented by PrEP beyond HIV prevention and enhance sexual and reproductive health (SRH) care to adolescents.