Outcomes of Modern Antiretroviral Therapy in Obese Individuals Living with HIV

Overview

Journal J Antimicrob Chemother

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2022 Nov 2

PMID 36322474

Authors

L Zino

J Stalenhoef

A Colbers

D M Burger

Affiliations

Soon will be listed here.

Abstract

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.

References

Caraco Y, Berry E, Levy M . Carbamazepine pharmacokinetics in obese and lean subjects. Ann Pharmacother. 1995; 29(9):843-7. DOI: 10.1177/106002809502900902. View

Eckard A, McComsey G . Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2019; 33(1):10-19. PMC: 7433018. DOI: 10.1097/QCO.0000000000000616. View

Jain R, Chung S, Jain L, Khurana M, Lau S, Lee J . Implications of obesity for drug therapy: limitations and challenges. Clin Pharmacol Ther. 2011; 90(1):77-89. DOI: 10.1038/clpt.2011.104. View

Brill M, van Rongen A, van Dongen E, van Ramshorst B, Hazebroek E, Darwich A . The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery. Pharm Res. 2015; 32(12):3927-36. PMC: 4628089. DOI: 10.1007/s11095-015-1752-9. View

Brill M, Diepstraten J, van Rongen A, van Kralingen S, van den Anker J, Knibbe C . Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012; 51(5):277-304. DOI: 10.2165/11599410-000000000-00000. View

Dupin N, Buffet M, Marcelin A, Lamotte C, Gorin I, Ait-Arkoub Z . HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy. AIDS. 2002; 16(18):2419-24. DOI: 10.1097/00002030-200212060-00006. View

Marzolini C, Sabin C, Raffi F, Siccardi M, Mussini C, Launay O . Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults. AIDS. 2014; 29(2):193-200. DOI: 10.1097/QAD.0000000000000530. View

Madelain V, Le M, Champenois K, Charpentier C, Landman R, Joly V . Impact of obesity on antiretroviral pharmacokinetics and immuno-virological response in HIV-infected patients: a case-control study. J Antimicrob Chemother. 2017; 72(4):1137-1146. PMC: 5517629. DOI: 10.1093/jac/dkw527. View

Moss D, Siccardi M, Murphy M, Piperakis M, Khoo S, Back D . Divalent metals and pH alter raltegravir disposition in vitro. Antimicrob Agents Chemother. 2012; 56(6):3020-6. PMC: 3370743. DOI: 10.1128/AAC.06407-11. View

10.

Muzard L, Alvarez J, Gbedo C, Czernichow S, Carette C . Tenofovir pharmacokinetic after sleeve-gastrectomy in four severely obese patients living with HIV. Obes Res Clin Pract. 2016; 11(1):108-113. DOI: 10.1016/j.orcp.2016.06.004. View

11.

Stohr W, Back D, Dunn D, Sabin C, Winston A, Gilson R . Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antivir Ther. 2008; 13(5):675-85. View

12.

Ang L, Ng O, Boudville I, Leo Y, Wong C . An observational study of the prevalence of metabolic syndrome in treatment-experienced people living with HIV in Singapore. PLoS One. 2021; 16(6):e0252320. PMC: 8171957. DOI: 10.1371/journal.pone.0252320. View

13.

Zarezadeh M, Saedisomeolia A, Shekarabi M, Khorshidi M, Emami M, Muller D . The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies. Eur J Nutr. 2020; 60(6):2905-2921. DOI: 10.1007/s00394-020-02421-y. View

14.

Marzolini C, Telenti A, Decosterd L, Greub G, Biollaz J, Buclin T . Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS. 2001; 15(1):71-5. DOI: 10.1097/00002030-200101050-00011. View

15.

Cheymol G . Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000; 39(3):215-31. DOI: 10.2165/00003088-200039030-00004. View

16.

Collis T, Devereux R, Roman M, De Simone G, Yeh J, Howard B . Relations of stroke volume and cardiac output to body composition: the strong heart study. Circulation. 2001; 103(6):820-5. DOI: 10.1161/01.cir.103.6.820. View

17.

Li X, Tan X, Cui X, Yang M, Chen C, Chen X . Pharmacokinetics of Tenofovir Alafenamide Fumarate and Tenofovir in the Chinese People: Effects of Non-Genetic Factors and Genetic Variations. Pharmgenomics Pers Med. 2021; 14:1315-1329. PMC: 8525415. DOI: 10.2147/PGPM.S329690. View

18.

Solas C, Poizot-Martin I, Drogoul M, Ravaux I, Dhiver C, Lafeuillade A . Therapeutic drug monitoring of lopinavir/ritonavir given alone or with a non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol. 2004; 57(4):436-40. PMC: 1884480. DOI: 10.1046/j.1365-2125.2003.02020.x. View

19.

Lloret-Linares C, Rahmoun Y, Lopes A, Chopin D, Simoneau G, Green A . Effect of body weight and composition on efavirenz, atazanavir or darunavir concentration. Therapie. 2018; 73(3):185-191. DOI: 10.1016/j.therap.2017.08.007. View

20.

de Roche M, Siccardi M, Stoeckle M, Livio F, Back D, Battegay M . Efavirenz in an obese HIV-infected patient--a report and an in vitro-in vivo extrapolation model indicate risk of underdosing. Antivir Ther. 2012; 17(7):1381-4. DOI: 10.3851/IMP2107. View