Is Descovy (emtricitabine and tenofovir alafenamide) or Apretude (cabotegravir) a better Pre-Exposure Prophylaxis (PrEP) option for a patient with impaired renal function (chronic kidney disease) and/or bone disease?

From the Guidelines

Descovy (emtricitabine and tenofovir alafenamide) is the preferred Pre-Exposure Prophylaxis (PrEP) option for patients with impaired renal function (chronic kidney disease) and/or bone disease due to its more favorable safety profile for renal and bone health. When considering PrEP options for patients with chronic kidney disease or bone disease, it is crucial to prioritize medications with a lower risk of exacerbating these conditions.

• The tenofovir alafenamide (TAF) component in Descovy results in lower circulating levels of tenofovir in the bloodstream, reducing potential toxicity to kidneys and bones, as noted in the 2020 recommendations of the international antiviral society-USA panel 1.
• For patients with CKD, Descovy can be used with estimated glomerular filtration rates (eGFR) as low as 30 mL/min, making it a more versatile option for patients with significant renal impairment, as recommended for the subset of men who have sex with men (MSM) with a creatinine clearance rate between 30 mL/min and below 60 mL/min who have a history of osteopenia or osteoporosis, or who are at high risk for these complications 1.
• Apretude (cabotegravir), while effective as a long-acting injectable given every two months, does not have the same established safety data for patients with significant kidney or bone disease, and its use is primarily recommended for cisgender men and transgender women who have sex with men (evidence rating: AIa) 1.
• The oral formulation of Descovy allows for easier discontinuation if side effects occur, whereas Apretude's long-acting nature means the medication remains in the system for months after injection.
• Monitoring for patients on Descovy should still include regular kidney function tests, typically every 3-6 months, even though the risk of renal complications is reduced compared to other options. Overall, the choice of Descovy over Apretude for patients with impaired renal function or bone disease is based on its pharmacological profile that minimizes additional risk to these systems, aligning with the goal of minimizing morbidity, mortality, and improving quality of life.

From the FDA Drug Label

Renal Impairment: No clinically significant differences in the pharmacokinetics of cabotegravir are expected with mild, moderate, or severe renal impairment.

The effect of hepatitis B and C virus co-infection on the pharmacokinetics of cabotegravir is unknown

Cabotegravir has not been studied in patients with end-stage renal disease not on dialysis.

As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures of cabotegravir

Cabotegravir (Apretude) may be a better option for a patient with impaired renal function, as no clinically significant differences in the pharmacokinetics are expected with mild, moderate, or severe renal impairment.

• However, it is essential to note that cabotegravir has not been studied in patients with end-stage renal disease not on dialysis.
• Additionally, the impact of bone disease on cabotegravir is not directly addressed in the provided label.
• Descovy (emtricitabine and tenofovir alafenamide) is not discussed in the provided label, so no comparison can be made. 2

From the Research

Comparison of Descovy and Apretude for PrEP in Patients with Impaired Renal Function and/or Bone Disease

• Descovy (emtricitabine and tenofovir alafenamide) has been shown to have improved renal and bone safety compared to tenofovir disoproxil fumarate-containing regimens 3, 4.
• Tenofovir alafenamide, a component of Descovy, has a 90% reduction in plasma tenofovir concentrations, which may contribute to its improved renal and bone safety profile 4.
• A meta-analysis of 14,894 patients across 14 trials found no significant differences in efficacy or safety between tenofovir alafenamide and tenofovir disoproxil fumarate, but noted a difference in risk for discontinuation due to renal adverse events in boosted regimens 5.
• Tenofovir alafenamide may be safer for the kidneys than tenofovir disoproxil fumarate, but long-term renal safety and safety in patients with chronic kidney disease require further study 6.

Considerations for Patients with Chronic Kidney Disease

• Patients with chronic kidney disease have an increased risk of osteoporotic fractures due to poor bone microarchitecture and tissue quality 7.
• Therapeutic interventions to improve bone health, such as those that affect bone turnover and mineralization, may be beneficial for patients with chronic kidney disease 7.
• The impact of Descovy and Apretude on bone quality and renal function in patients with impaired renal function and/or bone disease requires careful consideration and monitoring.

Apretude (Cabotegravir) Considerations

• There is limited information available on the use of Apretude for PrEP in patients with impaired renal function and/or bone disease.
• Cabotegravir, the active ingredient in Apretude, has a different mechanism of action and side effect profile compared to tenofovir alafenamide, and its effects on renal and bone health are not well established in the context of PrEP.