Department of Pharmacy, Radboud University Medical Center, and Radboud Institute for Health Sciences, Geert Grooteplein-Zuid 10 (route 864), P.O. Box 9101, 6500 HB, Nijmegen (864), The Netherlands.
Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.
Clin Pharmacokinet. 2022 May;61(5):619-635. doi: 10.1007/s40262-022-01120-7. Epub 2022 Apr 11.
Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV, sufficient antiretroviral exposure and activity should always be maintained to prevent development of resistance and disease progression. However, bariatric surgery procedures bring various gastrointestinal modifications including changes in gastric volume, and acidity, gastrointestinal emptying time, enterohepatic circulation and delayed entry of bile acids. These alterations may affect many aspects of antiretroviral pharmacokinetics. Some drug characteristics may result in subtherapeutic exposure and the potential related risk of treatment failure and resistance. Antiretrovirals that require low pH, administration of fatty meals, longer intestinal exposure, and an enterohepatic recirculation for their absorption may be most impacted by bariatric surgery procedures. Additionally, some antiretrovirals can interact with the polyvalent cations in supplements or drugs inhibiting gastric acid, thereby preventing their use as these comedications are commonly prescribed post-bariatric surgery. Predicting pharmacokinetics on the basis of drug characteristics solely proved to be challenging, therefore pharmacokinetic studies remain crucial in this population. Here, we discuss general implications of bariatric surgery on antiretroviral outcomes in people living with HIV as well as drug properties that are relevant for the choice of antiretroviral treatment in this special patient population. Additionally, we summarise studies that evaluated the pharmacokinetics of antiretrovirals post-bariatric surgery. Finally, we performed a comprehensive analysis of theoretical considerations and published pharmacokinetic and pharmacodynamic data to provide recommendations on antiretrovirals for people living with HIV undergoing bariatric surgery.
肥胖症手术在 HIV 感染者中越来越多地应用于降低肥胖症及其相关发病率和死亡率。在 HIV 感染者中,始终应保持充分的抗逆转录病毒暴露和活性,以防止耐药性和疾病进展。然而,肥胖症手术程序会引起各种胃肠道改变,包括胃容量和酸度、胃肠排空时间、肠肝循环和胆汁酸延迟进入的改变。这些改变可能会影响抗逆转录病毒药代动力学的许多方面。一些药物特征可能导致治疗失败和耐药性的潜在相关风险的治疗效果不佳。需要低 pH 值、给予高脂肪餐、更长的肠道暴露和肠肝再循环以吸收的抗逆转录病毒药物可能受到肥胖症手术程序的影响最大。此外,一些抗逆转录病毒药物可以与补充剂或抑制胃酸的药物中的多价阳离子相互作用,从而阻止它们的使用,因为这些药物通常是在肥胖症手术后开的。仅根据药物特征预测药代动力学证明具有挑战性,因此药代动力学研究在该人群中仍然至关重要。在这里,我们讨论了肥胖症手术对 HIV 感染者抗逆转录病毒治疗结果的一般影响,以及与该特殊患者人群中抗逆转录病毒治疗选择相关的药物特性。此外,我们总结了评估肥胖症手术后抗逆转录病毒药代动力学的研究。最后,我们对理论考虑因素和已发表的药代动力学和药效学数据进行了全面分析,为接受肥胖症手术的 HIV 感染者提供了抗逆转录病毒药物的建议。