Emtricitabine 200mg/tenofovir alafenamide 25mg tablets (Descovy®)

Tenofovir AF/emtricitabine (Descovy® or TAF/FTC) has been shown to be non-inferior to tenofovir DF/emtricitabine (TDF/FTC) in reducing incident HIV infections in a large, randomised clinical trial involving gay, bisexual and other men who have sex with men (GBMSM) and transgender women (TGW)¹⁰. Adverse effects on markers of bone mineral density and renal function were significantly reduced in the Descovy® arm¹¹. Extrapolated data and national guidance supports its use in individuals out with these groups including for vaginal intercourse and for blood-borne exposure in people who inject drugs (PWID)¹².

The Medicines and Healthcare products Regulatory Agency (MHRA) granted a license extension for Descovy®, at 200/25mg dosage, for PrEP in April 2022. This applies across the UK and means that use of Descovy® for PrEP is not ‘off label’, but it does not fall within the remit of Scottish Medicines Consortium. Prescribing in Scotland will therefore be through inclusion in local formularies or through non-formulary applications.  There is a significant cost implication in prescribing this regimen in place of generic TD/FTC, although the original cost benefit analysis supporting PrEP in Scotland was made using a list price for TDF PrEP (Truvada®), equivalent to the current list price for Descovy®. For patients where Descovy® is being considered as PrEP, it is advised that the case is discussed at a local or regional HIV/GUM MDT. Where it offers comparable levels of risk reduction for the individual, TTSS or ‘Ts & Ss’, event based or interval (‘holiday’) dosing of Tenofovir disoproxil/emtricitabine should be trialled where possible.  It is recommended that those under the age of 18 years should be offered TAF/FTC as PrEP and as bone formation continues into the early 20s, TAF/FTC PrEP when commenced before the age of 18 years should be continued until the individual is aged 20 years. In cases where indications are not clear, referral for discussion at the Scottish national complex PrEP MDT should be made and the decision documented and recorded.  

The following scenarios may warrant consideration of starting or switching to Descovy® PrEP in individuals who fulfil the Eligibility criteria for Tenofovir AF/emtricitabine (Descovy®) for pre-exposure prophylaxis for HIV (PrEP) in Scotland¹².  

• Renal: high risk factors for TD/FTC: or moderate or severe reduction in glomerular filtration (estimated glomerular filtration rate [eGFR] ≤ 59 ml/min2, at baseline or during follow-up) and clinical assessment suggests that TAF/FTC would have a lower risk profile than TD/FTC OR in individuals with proven renal toxicity with TD/FTC (acute or chronic)^*.
• Renal: medium risk factors for TD/FTC: Individuals with an eGFR ≥ 60 ml/min2 in which: a progressive reduction in estimated glomerular filtration rate on TD/FTC is seen AND significant concurrent medical issues or monitoring/prescribing concerns that suggest TAF/FTC would have a lower risk profile to TD/FTC^**.
• Bone: high risk factors for TD/FTC: Individuals with confirmed osteoporosis on DEXA or a high risk of a major fracture as determined by an appropriate fragility risk score. Note: high fracture probability defined as > 10% (major osteoporotic or hip fracture absolute risk), with NICE recommending QFracture or FRAX scores. 
• Bone: medium risk factors for TD/FTC: Individuals who are < 18 years. Note: markers of increased absolute fracture risk include previous vertebral fracture(s), high alcohol intake, high-dose oral or high-dose systemic glucocorticoids (more than 7.5 mg prednisolone or equivalent per day for 3 months or longer) or other causes of secondary osteoporosis^13,14.
• Gastrointestinal intolerance/swallowing difficulties: There is no evidence base for changes made for GI intolerance, nor any evidence that Descovy® PrEP has better GI tolerability than TD/FTC PrEP. Any changes should be based on clinical experience and with MDT input. A list of excipients for all available TD/FTC formulations is available.

* Renal toxicity defined as a progressive, sustained decline in renal function or development of renal tubular acidosis, attributable to TD-FTC. Toxicity could also include development or worsening of existing proteinuria without another reversible or explained cause. It is expected that prescribers can consult renal specialists if there is diagnostic uncertainty.

** A reduction in eGFR of 15ml/min in the past 12 months or 25% reduction in eGFR in the past 12 months were determined to be significant threshold measures by NHS England Specialist Commissioning HIV Clinical Reference Group (HIV [CRG]) working group.

Any reduction in eGFR of clinical concern should be confirmed at least once on a repeat sample before changing dosing or preparation, after confirming that any creatine and protein supplements have been discontinued.   

• A confirmed reduction of 15mL/min or 25% in eGFR from baseline to 60-69mL/min is an indication for consideration of a non-TDF PrEP (alternative TDF dosing may be considered)¹².
• A confirmed reduction of 15mL/min or 25% in eGFR from baseline to >70-89ml/min is an indication for 3 monthly recheck of eGFR.
• In those over 50 years, risk factors for reduced bone mineral density should be assessed at baseline. 
• In those with risk factors for reduced BMD over 50 years, the FRAX tool could be undertaken, to indicate the need for a DEXA scan.