Implementation of HIV prevention strategies globally

Although pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine was first approved by the US Food and Drug Administration in 2012, uptake of PrEP has been slow, with challenges at many levels, including policy development, implementation, and societal acceptance. Innovations in PrEP delivery, such as community-based delivery and self-care interventions could address some of these challenges for improved oral PrEP use. A priority for the HIV prevention community is to implement differentiated service delivery models and pursue innovations to improve the uptake and persistence of oral PrEP. However, HIV epidemic control (ie, the point at which the total number of new HIV infections is less than the total number of deaths from all causes among people living with HIV, with both new infections and deaths low and declining) will be hard to realise with primary prevention limited to daily oral PrEP tablets. In addition, there are many barriers to uptake, including limited access, an inaccurate perceived risk of HIV acquisition, stigma, medical mistrust, and difficulties consistently taking a daily pill.¹

A choice of prevention options is necessary to meet the needs of the diverse populations who might benefit from PrEP. Thus, biomedical HIV prevention with different formulations and modalities have been under development,² with two recently (2016–21) demonstrating effectiveness—the monthly dapivirine vaginal ring and long-acting injectable cabotegravir. Adolescent girls and young women and other key populations (eg, men who have sex with men, female sex workers, people who use injection drugs, and transgender people) are often not aware of and cannot access oral PrEP; stigma and pill burden have posed challenges with initiating and persisting on PrEP.¹ Therefore, long acting and more discreet options might be preferred.

In 2016, the ASPIRE trial³ showed that dapivirine rings are safe and lowered the incidence of HIV by 27%, with increased efficacy among subgroups with higher adherence.³ Open-label extension studies subsequently showed high uptake and persistent use of the ring with improved adherence, effectiveness, and high acceptability among African women.^4,5 WHO prequalified the dapivirine ring in 2021, and many countries adapted their policies to allow for implementation of the ring and to offer an additional choice to women for HIV prevention. Adolescent girls and young women are disproportionately affected by HIV in sub-Saharan Africa and have an unmet need for HIV prevention; the REACH (MTN 034)⁶ crossover study showed participants could use both oral PrEP and the dapivirine ring with high adherence when given a choice and offered several options for adherence support.⁶ Two-thirds of participants chose the ring after having used both methods for 6 months each.⁶ The efficacy of dapivirine rings is high when used correctly and consistently. Effective use of a PrEP product during periods of possible exposure to HIV is important; thus the ease of adherence to the dapivirine ring compared with use of oral PrEP is an essential consideration, and the ring might be a viable option for women because they are replaced monthly. If adolescent girls and young women are comfortable using dapivirine rings, it might lead to better coverage and protection compared with nothing, or with suboptimal adherence to oral PrEP. Modelling studies showed dapivirine rings could be cost-effective in high-incidence settings, such as KwaZulu-Natal, and cost-saving if priority is given to sex workers.^7,8

In 2021, the FDA approved long-acting cabotegravir, which was highly effective, safe, and superior to oral tenofovir and emtricitabine among men who have sex with men, and transgender and cisgender women who have sex with men.^9,10 Although long-acting cabotegravir was highly effective in all study populations and breakthrough infections were rare, delayed diagnosis of a small number of incident infections with risk of integrase inhibitor resistance presents a real challenge for implementation, particularly in low-resource settings with limited HIV RNA laboratory monitoring. The logistics and higher cost of service delivery pose further barriers, given the need for specialised training to administer injections. Additionally, oral PrEP must be given to people with ongoing risk during the long pharmacokinetic tail if they miss doses, cannot access, or discontinue CAB-LA.

Ideally, all prevention options should be available to people susceptible to HIV acquisition. However, logistics and cost might restrict availability of dapivirine rings and long-acting cabotegravir for years to come, possibly hindering HIV epidemic control in many high-burden countries. Therefore, public health authorities should consider innovative delivery approaches for continued use and improved outcomes of oral PrEP. Demand creation and education that assess the need for oral PrEP will facilitate uptake of other biomedical prevention modalities. Also, implementation needs (table) and essential operations research necessary to facilitate timely roll-out of new biomedical prevention modalities should be considered. Key issues for implementation include educating users about the relative effectiveness of products and understanding the utility of products with lower effectiveness as another option for individuals who are non-adherent to daily oral PrEP. Without concerted action and thoughtful attention to all aspects of implementation and service delivery, the potential of the dapivirine ring and long-acting cabotegravir to increase PrEP coverage and to achieve population-level impacts on HIV prevention might not be realised. The field of biomedical prevention is dynamic, and as new modalities become available it is important to help individuals recognise how characteristics of different prevention options might suit their own lifestyle, so that personalised optimal HIV prevention becomes a reality.

Table:

Implementation needs for successful roll-out and programming of new biomedical prevention modalities in low-resource settings

	Description of needs
Societal and policy
Resource mobilisation and budget	Ensure funding and other resources are available for implementation; there is the potential for programmatic prioritisation or trade-offs in resource-constrained or zero-sum resource environments
Policies and guidelines	Develop timely enabling policies and guidelines reflecting stakeholder buy-ins
Regulatory approvals	Support the regulatory approval of modalities as needed
Environment
Demand creation and education	Conduct education campaigns about different modalities
Stigma	Offer PrEP with approaches that minimise stigma and discrimination
Institutional
Supply chain and procurement	Leverage systems to ensure that new modalities and related diagnostics and supplies are affordable and accessible
Service delivery	Promote informed choices of PrEP options and integrate into systems that reach the intended recipients; integrate PrEP with sexual and reproductive health programmes (including the provision of sexually transmitted infection services, contraception, and gender-affirming hormones)
Implementation science	Run cost-effectiveness analyses and formative assessments of differentiated service delivery models and other programmes such as antenatal care and voluntary medical male circumsion clinics, considering populations, such as women and other pregnant or breastfeeding people; pilot the feasibility of offering the ring and long-acting PrEP in pharmacies and other community-based PrEP delivery models, and other differentiated prevention considerations, such as clinics that are specifically set up to provide injections; assess and evaluate acceptability of modalities by recipients and health-care workers; define larger comprehensive strategies for switching from one modality to another
Monitoring and evaluation	Establish monitoring and evaluation systems for uptake, persistence, and adverse reactions, including delayed diagnosis and drug resistance in breakthrough infections; establish pharmacovigilance for PrEP use during pregnancy and breastfeeding, with pregnancy and infant outcomes; evaluate the risk of drug resistance and need for RNA testing; evaluate systems routinely for quality improvement; assess their effect on HIV epidemic control
Interpersonal
Client tools	Develop and implement infographics about attributes of PrEP products and client-facing decision support tools
Training	Regular training of health-care providers and counsellors, including regarding client-centred decision making and PrEP options, relative effectiveness, side-effects, and monitoring
Intrapersonal
Education	Individuals should understand their risk for HIV infection and know available prevention options