Case report: Dolutegravir dosing post-Roux-en-Y gastric bypass surgery

Abstract

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Case report: Dolutegravir dosing post-Roux-en-Y gastric bypass surgery

Jennifer Hawkes

Northern Health

Background: Adequacy of dolutegravir drug exposure when administered after the duodenum (such as Roux-en-Y jejunostomy tube or Roux-en-Y gastric bypass surgery) is largely unknown. In addition, various gastrointestinal modifications including changes in gastric volume, acidity, emptying time, enterohepatic circulation and delayed entry of bile acids may be present post-surgery. Existing data are limited to individual case reports or case series with the timing of collection post-surgery varying. Pharmacokinetics are more likely to be altered in the early stages post-surgery. There is evidence of decreased exposure of dolutegravir following a Roux-en-Y gastric bypass surgery. In some cases, a temporary increase in dolutegravir dose to 50 mg BID may be considered.

Case report: A 53-year-old white male with HIV on antiretroviral therapy with dolutegravir/abacavir/lamivudine FDC and recent non-adherence with 1 month of missed doses is admitted for emergency Roux-en-Y gastric bypass surgery due to a septic shock and perforated gastric viscus with a suspected gastric tumour. He is non-obese and had a low BMI of 18.5. He was not virologically suppressed at the time of the surgery with an HIV VL 560 copies/mL and a CD4 count of 160 cells/mm³. The dolutegravir dose was increased to 50 mg BID with food post-surgery to mitigate potential decreased levels. Dolutegravir trough levels were measured at 7 days' post-dose increase (steady state), which was 2 weeks' post-surgery. A reduction in dolutegravir trough concentrations were observed compared to reference C_min levels prior to the AM dose but not the supper dose (1137 and 2167 ng/mL vs. reference of 2120 ng/mL). A target dolutegravir trough has not yet been established nor has a dose limiting toxicity. His HIV viral load re-suppressed to <40 copies/mL at 1 month post-surgery and has remained suppressed at 2, 3 and 5 months' post-surgery with an increase of CD4 cells to 290 cells/mm³ at 5 months' post-surgery.

It was decided to continue dolutegravir BID long term in this patient due to one level being at reference and one below reference, the challenges with obtaining new steady-state levels, tolerability of the regimen and ongoing intermittent non-adherence.

Conclusion: This case study continues to highlight the importance of performing pharmacokinetic assessments in patients with the potential for impaired drug absorption to ensure antiretroviral success. Dolutegravir BID has been shown to be well tolerated for long-term use; however, there is the potential to reduce the dose in the future based on adherence and therapeutic drug monitoring.