Cabotegravir

Background 

Injectable PrEP with cabotegravir is highly effective in preventing HIV transmission. It is indicated for adults and adolescents at risk of HIV transmission but for whom oral PrEP is not appropriate to meet their HIV prevention needs. It was accepted for use within NHS Scotland in February 2025. 

Cabotegravir was found to be superior to daily oral tenofovir disoproxil fumarate/emtricitabine in the reduction of incident HIV acquisitions in a phase IIb/III study in men who have sex with men and transgender women by 66% (HPTN 083) and in a phase III study in heterosexual cisgender women at high risk of acquiring HIV by 89% (HPTN 084)^16,17,18. 

There was no placebo arm in the HPTN-083 and 084 trials but an indirect treatment comparison suggests that cabotegravir has superior efficacy compared with no PrEP in reducing the risk of HIV acquisition: the relative estimated effectiveness was 91% (97.5% credible interval [Crl]: 83% to 96%) in men who have sex with men and transgender women (HPTN 083 population), and 92% (97.5% Crl: 83% to 97%) in heterosexual cisgender women (HPTN 084 population)¹⁹. 

There is however  a significant resource implication in prescribing this regimen in place of generic Tenofovir DF/Emtricitabine PrEP both in terms of drug costs and appointment requirements. A Patient Access Scheme (PAS) was submitted by the company and assessed by the Patient Access Scheme Assessment Group (PASAG) as acceptable for implementation in NHS Scotland.  

Eligibility considerations  

Use of cabotegravir should be reserved for adolescent and adults with an increased risk of HIV acquisition that cannot safely or reliably take daily or event-based doses of oral PrEP because of medical, demographic or social reasons.   

It is recommended that all dosing options including daily, TTSS or ‘Ts & Ss’, and event based (2:1:1 or 2:7 dosing according to exposure type) for TD/FTC and TAF/FTC are considered and/or trialled before injectable PrEP is considered.  

For individuals where cabotegravir is being considered as PrEP, it is advised that the case is discussed at a local or regional HIV/GUM MDT. Cases may also be referred for discussion at the Scottish national complex PrEP MDT.

Individuals need to agree to the 2-month injection dosing schedule because non-adherence or missed doses could lead to HIV acquisition and development of drug resistance. Furthermore a reactive HIV antibody screening test has been shown in rare cases to be delayed in those taking Cabotegravir PrEP warranting the need for HIV viral load testing, in addition antibody testing.  

Counselling should cover the following points;  

Increased clinic visits compared to oral PrEP requirements 

• Cabotegravir is approved as a gluteal intramuscular injection given by a healthcare professional, initiated monthly for 2 months and then continued with an injection every 2 months thereafter.  

Importance of adherence and stopping rules  

• Protective levels of cabotegravir are achieved 7 days after the first injection and maintained for 8 weeks after the last injection  

• Individuals who miss a scheduled injection visit should be clinically reassessed to ensure resumption of cabotegravir remains appropriate  

• If cabotegravir  is discontinued and HIV prevention is still required, it is preferable that an alternative PrEP agent is initiated, starting at 8 weeks and continuing to at least 52 weeks after the last cabotegravir injection 

Increased blood testing compared to oral PrEP requirements 

• In addition to routine testing, it is recommended that individuals on cabotegravir have HIV antibody-antigen and HIV viral load testing every 8 weeks. Laboratory teams need to be notified that testing is for cabotegravir PrEP and not HIV monitoring. 

Side effects 

• Individuals can choose to have a 4-week lead-in period of 30 mg daily oral cabotegravir prior to the first injection if they are worried about side effects. Studies have confirmed that cabotegravir is well-tolerated with a safety profile similar to that of oral PrEP (TDF/FTC), with the exception of injection site reactions. Injection site pain was the most frequently reported injection site reaction (ISR) in the cabotegravir group in both studies (HPTN 083: 81%; HPTN 084: 34%); injection site nodule, induration and swelling were also commonly reported. In general, reactions decreased in severity and frequency over time^15,18.