Purpose

Ending the HIV epidemic as a public health threat requires high-impact HIV prevention and testing services. Pre-exposure prophylaxis (PrEP) is a key component of combination HIV prevention. For people at substantial risk of HIV, the World Health Organization (WHO) in 2015 recommended oral PrEP containing tenofovir disoproxil fumarate (TDF), in 2021 the dapivirine vaginal ring (DVR) for cisgender women at substantial risk of HIV and in 2022 the long-acting injectable cabotegravir (CAB-LA). Expansion of access to and use of oral PrEP have accelerated in recent years, and more countries have included CAB-LA and the DVR in their national guidelines and have begun programmatic implementation.

Potential barriers to the uptake and effective use of oral PrEP, as well as CAB-LA and the DVR, include not wanting to take an oral pill regularly and desire for less frequent clinic visits. These barriers may be overcome with new PrEP products that offer protection for longer periods of time. With these guidelines, WHO recommends offering the six-monthly injectable lenacapavir (LEN) as an additional HIV prevention option. Offering additional PrEP choices has the potential to increase uptake and effective use of PrEP and of HIV prevention overall, as it allows people to choose a method that they prefer.

With these guidelines, WHO recommends offering the six-monthly injectable lenacapavir (LEN) as an additional HIV prevention option.

Testing services are a critical component of PrEP delivery. Effective and efficient testing services can help streamline service provision and support a broader public health approach. To ensure effective and equitable access to PrEP, HIV testing services should be feasible, accessible and scalable. These guidelines highlight the latest evidence on the benefits of using simple rapid diagnostic tests (RDTs) when providing long-acting injectable PrEP, rather than more complex and costly nucleic acid testing (NAT) techniques or laboratory-based testing. Simplified testing approaches reduce barriers, minimize delays, improve sustainability and reduce per-test cost.

WHO continues to recommend HIV RDTs and HIV self-testing (HIVST) as part of standard HIV testing services. With these guidelines, WHO recommends using HIV RDTs for individuals initiating or continuing long-acting injectable PrEP, such as CAB-LA and LEN. HIVST remains a recommended option for oral PrEP, the DVR and post-exposure prophylaxis (PEP), as it may offer additional flexibility across PrEP programmes. Further implementation research is needed to fully determine the role of HIVST in delivering long-acting injectable PrEP.

Flexible HIV testing approaches are essential for ensuring that testing does not become a barrier to accessing or continuing PrEP, including long-acting injectable options. Aligning testing frequency with PrEP refill and injection visit schedules is often practical. To enhance access and choice, alternative testing schedules may also be needed and can be considered, particularly as part of efforts to adopt simplified and differentiated PrEP delivery (for example, greater task sharing, multi-month dispensing, pharmacy PrEP, TelePrEP and other online distribution models).

The primary audience for this guideline is national and subnational programme managers and policy-makers responsible for the national health sector response to HIV, particularly in low- and middle-income countries.

Guideline development methodology

In response to emerging new evidence on the efficacy of LEN for the prevention of HIV acquisition across diverse populations, and on testing for long-acting prevention products, the WHO Department of Global HIV, Hepatitis and Sexually Transmitted Infections Programmes led the development of new guidance, with support from the Guideline Development Group (GDG) and External Review Group, from January to May 2025.

The WHO steering group formulated two population, intervention, comparator, outcome (PICO) questions, one on LEN as PrEP and another on the use of RDTs in the context of long-acting prevention. External researchers, supported by WHO, conducted the systematic reviews of the evidence to answer these questions. They synthesized the evidence and incorporated it into an evidence-to-decision framework to help inform the discussions at a virtual GDG meeting that occurred over three days from 28 to 30 January 2025, chaired by two members of the GDG and facilitated by an independent methodologist. The GDG members made judgements on the potential benefits and harms of the intervention, stakeholder values and preferences, acceptability, feasibility, resource use and considerations of human rights and equity. Taken together and using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, these judgements contributed to determining the strength and direction of the recommendations. The recommendations were formulated through consensus.

New recommendations

The GDG concluded that, at the time of convening, there was insufficient evidence to recommend HIV self-testing for long-acting injectable PrEP (LA-PrEP). Evidence reviewed did suggest, however, that HIVST could increase flexibility and testing frequency as well as further decentralize testing access. Further implementation research is needed to understand the potential role of HIVST within LA-PrEP. HIVST continues to be recommended for oral PrEP, the DVR and PEP.

Implications for implementation

LEN should be delivered as an additional choice alongside other HIV PrEP and prevention options. As countries plan for the introduction of LEN, considerations should include differentiated service delivery models and integration to maximize acceptability and accessibility; population-specific needs; awareness raising and demand generation activities; provider training. At the same time, monitoring and surveillance systems should be designed, to support safety and service quality improvement such as adverse event monitoring during pregnancy and breastfeeding, seroconversions and drug resistance; and the relative costs and potential of LEN to achieve impact. Successful introduction of LEN will be enhanced by the full participation of communities in designing, implementing and monitoring programmes.

Availability of LEN to date has been restricted to trial settings, and the follow-up time has been limited. There are evidence gaps regarding the optimal testing strategies, the best approaches to support access, adherence to the dosing schedule, persistence, alternative dosing and administration, product switching, ideal provision in some populations and geographies, and the costs and impacts of LEN. However, the GDG stressed that, despite the evidence gaps identified, further research should not delay the programmatic implementation of LEN in countries.

Simple HIV testing strategies that rely on RDTs and are aligned to WHO guidance are needed to support injectable LA-PrEP implementation within broader PrEP programmes. Adopting this approach will provide consistency, quality and efficiency to programmes and enable countries to use their standard national testing algorithm. Using HIV RDTs also makes it possible to provide same-day injectable LA-PrEP initiation and, thus, to facilitate effective and continuous use.