NICE Draft Guidance Rejects Lenacapavir for HIV PrEP in England

NICE has opened a consultation on draft guidance that does not recommend lenacapavir for HIV PrEP. The evaluation committee found the six-monthly injection is not value for money for the NHS in England on the evidence it reviewed.

The draft recommendation

The draft says lenacapavir should not be used as pre-exposure prophylaxis (PrEP) alongside safer sex practices in adults and young people at high risk of HIV-1 who weigh at least 35 kg. If the recommendation becomes final, lenacapavir would not be routinely funded in England. Treatment already started in the NHS before publication is unaffected.

Where the injection fits

Most people at high risk of HIV take daily oral PrEP, usually tenofovir disoproxil fumarate plus emtricitabine (TDF-FTC). Those who cannot take oral PrEP can have cabotegravir, an injection given every two months. Lenacapavir (Yeytuo, Gilead Sciences) is a longer-acting option given every six months. Its marketing authorisation covers adults and adolescents at increased risk of HIV-1 who weigh at least 35 kg.

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The evidence for lenacapavir for HIV PrEP

The clinical case rested on the PURPOSE 1 and PURPOSE 2 randomised controlled trials. PURPOSE 1 enrolled cis women aged 16 to 25 in South Africa and Uganda (n=5,338), with data collected from August 2021 to August 2023. PURPOSE 2 enrolled cis men, trans women, trans men and non-binary people aged 16 and over who have sex with men, across the US, Brazil, Thailand, South Africa, Peru, Argentina and Mexico (n=3,265), with data collected from June 2021 to December 2023.

In the in-study analysis, lenacapavir recorded 0 HIV infections per 100 person-years in PURPOSE 1 (95% confidence interval 0.00 to 0.19), against 1.69 for TDF-FTC (0.96 to 2.74). In PURPOSE 2, lenacapavir recorded 0.1 per 100 person-years (0.01 to 0.37) against 0.93 for TDF-FTC (0.43 to 1.77). The committee concluded that lenacapavir reduces HIV acquisition compared with TDF-FTC.

Cost effectiveness

There was no direct trial comparing lenacapavir with cabotegravir, so the external assessment group used an indirect treatment comparison rated as very low certainty. The committee preferred a baseline HIV acquisition risk of 1.9 per 100 person-years, drawn from UK Health Security Agency data on gay, bisexual and other men who have sex with men attending sexual health services in England in 2022 to 2023.

Both the company’s and the assessment group’s models produced incremental cost-effectiveness ratios above £35,000 per quality-adjusted life year. That sits above the range NICE considers an acceptable use of NHS resources, around £25,000 to £35,000 per QALY. The exact ratios and the list price for lenacapavir are commercial in confidence.

Uncertainty and equality

The committee flagged several uncertainties, including how well the trial populations reflect the UK population and how to model the effect of HIV and its treatment on quality of life. Stakeholders noted that people at high risk include Black African people, trans people, migrants, sex workers, people in unstable housing and gay or bisexual men. The committee acknowledged that long-acting injections may help some underserved groups, but said a recommendation could not directly address access to services.

What happens next

This is not NICE’s final guidance. Stakeholders and the public can comment until 30 September 2026. A second evaluation committee meeting follows on 3 November 2026, after which NICE will prepare final draft guidance. The topic was considered by committee C, chaired by James Fotheringham.