PrEP-LANA (Pre-exposure Prophylaxis- Long-acting Novel Antiviral Agent)

Background

The introduction of pre-exposure prophylaxis (PrEP) marked a major scientific advance in HIV prevention. However, its public health value depends on whether individuals at risk feel able to access it and remain protected over time. In the UK, this is not currently realised equally across population groups. The UK Health Security Agency reported that in 2024, PrEP initiation or continuation among people with a PrEP need was 79.4% in White gay and bisexual men and 77.8% in ethnic minority gay and bisexual men, but much lower in Black African heterosexual women (34.6%), Black African heterosexual men (36.4%), and other ethnic minority heterosexual adults (43.9%). (1) PrEP delivery approaches are yet to address these inequities.

Daily oral tenofovir-based PrEP (TDF/FTC) remains the standard PrEP option in the UK. (2) However, its effectiveness depends on consistent use over time. This is often not achieved in practice. For example, a meta-analysis of 59 longitudinal studies involving 43,917 participants initiating oral PrEP globally found that 41.0% discontinued within 6 months and 37.7% had suboptimal adherence over the same period. (3) It has been suggested since 2018 that adherence to oral PrEP is particularly challenging for cisgender women and younger people. (4) This is supported by recent trial data. In HPTN 082, a randomised study of daily oral PrEP among adolescent girls and young women in South Africa and Zimbabwe, 95% initiated oral PrEP, but only 21% had drug levels consistent with high adherence at month 6, with this number dropping to 9% at month 12. (5) In HPTN 084, a phase 3 randomised trial conducted at 20 sites across seven sub-Saharan African countries among cisgender women, adherence was similarly low, with only 42.1% of plasma samples in a random subset consistent with daily use. (6) Daily oral dosing is also recognised as harder to sustain for individuals who struggle with oral medicines or regular engagement with services, and those experiencing homelessness, unstable housing, or intimate partner violence. (7) Taken together, these findings suggest that service models built primarily around daily oral PrEP leave some populations with less protection against HIV acquisition.

Long-acting injectable cabotegravir (LA CAB) offers an alternative PrEP modality. (7) On 5 November 2025, NICE recommended LA CAB for preventing HIV-1 in adults and young people at high risk of sexually acquired HIV-1 infection who cannot have oral PrEP. (7) This includes people for whom oral PrEP is medically contraindicated, people who cannot take tablets, and people for whom oral PrEP is unsuitable because of social or personal circumstances. (7) Superior efficacy of LA CAB compared with daily oral TDF/FTC has been demonstrated in two large, randomised trials. HPTN 083, conducted across sites in the United States, Latin America, Asia and Africa among cisgender men and transgender women who have sex with men, found that LA CAB was superior to daily oral TDF/FTC for HIV prevention. (8) In the blinded phase of HPTN 083, 91.5% of person-years were covered by on-time injections. (8) In the oral TDF/FTC arm, 74.2% of participants had plasma tenofovir concentrations consistent with daily dosing. (9) HPTN 084, conducted in sub-Saharan Africa among cisgender women, found HIV incidence of 0.20 versus 1.85 per 100 person-years, corresponding to an 88% lower risk of HIV acquisition with cabotegravir. (6) Injection coverage in HPTN 084 reached 93% of person-years, whereas 42.1% of plasma samples in a random subset of the oral TDF/FTC group were consistent with daily use. (6) These trials establish LA CAB as a more efficacious PrEP option than daily oral TDF/FTC in the populations studied. Furthermore, data modelling the impact of rapid LAI PrEP scale up in men who have sex with men in the Netherlands, demonstrated that offering individuals LAI PrEP had the potential to avert between 14-21% of new infections within 10 years of introduction. (10) US modelling estimates similarly suggest that LAI PrEP could reduce HIV incidence by 4%-36% over a 10-year period. (11,12) Early implementation data suggest that LA CAB can be delivered effectively, acceptably, and feasibly in routine practice, but the evidence base remains limited. In a two-clinic Italian implementation report, LA CAB was offered to 265 people prioritised because of barriers to oral PrEP, with injection adherence (defined as injections within a 7-day window) exceeding 95%, favourable tolerability, and only 1.5% discontinuing because of drug-related reasons. (13) In another Italian study, a prospective real-world cohort from Milan, LA CAB PrEP was associated with high acceptability and improved perceived adherence, convenience and HIV protection, although the cohort was almost exclusively cisgender men who have sex with men and most participants had prior oral PrEP experience. (14) In the Trio Health cohort in the United States, no incident HIV diagnoses were identified among 526 LA CAB PrEP users, and reported persistence was 92% at 6 months and 85% at 12 months. (15) However, these persistence estimates remain uncertain, due to limitations in follow-up and overlap in how adherence and persistence were defined. (7) Interim patient findings from the EBONI study among Black cisgender and transgender women in the United States likewise suggest high acceptability and feasibility, while interim healthcare provider findings indicate that delivery depends on staff preparation, workable local pathways, and reminder or tracking systems. (16,17) Formative implementation work from ImPrEP CAB Brazil similarly identified the need for service-delivery optimisation, including visit duration, staff training, support for injection appointments, and the value of educational and reminder tools. (18)

5.2. Rationale