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.
Background
Implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with HIV (PWH) on antiretroviral therapy (ART) is unrevealed. The ATHENA cohort collects data on PWH from all Dutch HIV treating centers.
Methods
We report a retrospective analysis up to 18-months post-BS in PWH from ATHENA cohort. Primary endpoints were a confirmed virologic failure (two consecutive HIV-RNA >200 copies/mL); and the percentage of subjects achieving >20% total body weight loss up to 18-months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS.
Results
Fifty-one subjects were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18-months post-BS. Eighty-five percent of subjects achieved >20% loss of total body weight at 18-months post-BS with mean difference from baseline (95% CI) at -33.5% (-37.7% to -29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except one sample of darunavir. Lipids profile, but not serum creatinine and blood pressure, improved significantly (p<0.01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 drugs and from 62 to 25, respectively at 18-months post-BS.
Conclusion
BS was an effective intervention for weight loss and lipids control in PWH using ART in this cohort with no clear link to a poor virologic outcomes.
Obesity is a global epidemic and people living with HIV (PLWH) are showing similar obesity trends to those in the general population. Obesity is manifested by several physiological features that can alter volume of distribution, elimination and metabolism of various medications including ART. Some drugs are increasingly prone to pharmacokinetic alteration during obesity depending on their physicochemical properties and clearance mechanism. These considerations raise concerns of hampered efficacy, development of resistance or increased toxicity of ART in PLWH. Here, we summarize available literature on the exposure and antiviral outcomes of currently available antiretroviral drugs in the context of obesity and provide a panel of recommendations for the clinical management and follow-up in this growing patient population.
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