Antiretrovirals and frequently prescribed medications in people living with HIV: Potential drug-drug interactions detected by three online-databases

Main Article Content

Apisada Jiso
Kanaporn Thiengtham
Athikhun Suwannakhan
Nunnaphat Sirijaraswan
Phisit Khemawoot
Somnuek Sungkanuparph

Keywords

drug interactions, antiretrovirals, metabolic syndrome, micromedex, drugs.com, liverpool HIV drug interactions checker

Abstract

Background: Since the advent of antiretroviral therapy, HIV infection, which was once considered a life-threatening condition, can now be managed as a chronic disease. People infected with HIV have high prevalence rates of comorbid illnesses, including cardiovascular diseases, cancers, diabetes, dyslipidemia, chronic renal disease, and chronic liver disease. Comedication of antiretrovirals and frequently prescribed medications for comorbid illness could cause serious drug-drug interactions (DDIs). Objective: To evaluate the level of agreement among the drug interaction tools of three databases (Micromedex, Drugs.com, and Liverpool HIV Drug Interactions Checker) for potential DDIs detection. Methods: Drugs were selected from National List of Essential Medicines of Thailand (2021) and the Ramadhibodi Chakri Naruebodindra Hospital drug list. Potential DDIs were identified by the three databases. The agreement was determined by Fleiss’ kappa. Results: Seventeen antiretrovirals and 77 frequently prescribed medications from the National List of Essential Medicines of Thailand (2021) and the Ramadhibodi Chakri Naruebodindra Hospital drug list were included in this study. Overall, 383 pairs of potential DDIs were detected by the three databases. Drugs.com reported the highest number of DDIs (302 pairs), followed by the Liverpool (222 pairs) and Micromedex (160 pairs) databases. Among these DDIs, 113 pairs (29.5%) were reported as contraindicated or major severity in all three databases. The major DDI mechanisms were pharmacokinetic-based cytochrome P450 inhibition (33.4%) and induction (20.1%). Fleiss’ kappa agreements were slightly concordant among the three databases (0.0476). Conclusions: Healthcare provider vigilance is important to manage the potentially varying DDI information in different databases that could impact the safety and efficacy of HIV treatment.

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References

1. UNAIDS. Global HIV & AIDS statistics — Fact sheet: UNAIDS 2022 [cited 2022 12 Oct 2022]. Available from: https://www. unaids.org/en/resources/fact-sheet.
2. Thailand National Guidelines on HIV/AIDS Diagnosis, Treatment and Prevention 2020/2021. Department of Disease Control, Ministry of Public Health, Thailand; 2020. 
3. Lagathu C, Kim M, Maachi M, et al. HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo. Biochimie. 2005;87(1):65-71. https://doi.org/10.1016/j.biochi.2004.12.007
4. Lee GA, Rao MN, Grunfeld C. The effects of HIV protease inhibitors on carbohydrate and lipid metabolism. Curr HIV/AIDS Rep. 2005;2(1):39-50. https://doi.org/10.1007/s11904-996-0008-z
5. Riddle TM, Schildmeyer NM, Phan C, et al. The HIV protease inhibitor ritonavir increases lipoprotein production and has no effect on lipoprotein clearance in mice. J Lipid Res. 2002;43(9):1458-63. https://doi.org/10.1194/jlr.M200129-JLR200
6. Noubissi EC, Katte J-C, Sobngwi E. Diabetes and HIV. Curr Diab Rep. 2018;18(11):125. https://doi.org/10.1007/s11892-018- 1076-3
7. Shah ASV, Stelzle D, Lee KK, et al. Global burden of atherosclerotic cardiovascular disease in people living with HIV. Circulation. 2018;138(11):1100-12. https://doi.org/10.1161/CIRCULATIONAHA.117.033369
8. Nguyen TMD. Adiponectin: Role in physiology and pathophysiology. Int J Prev Med. 2020;11:136. https://doi.org/10.4103/ ijpvm.IJPVM_193_20
9. Flint OP, Noor MA, Hruz PW, et al. The role of protease inhibitors in the pathogenesis of HIV-associated lipodystrophy: Cellular mechanisms and clinical implications. Toxicol Pathol. 2009;37(1):65-77. https://doi.org/10.1177/0192623308327119
10. Paula AA, Falcão MCN, Pacheco AG. Metabolic syndrome in HIV-infected individuals: underlying mechanisms and epidemiological aspects. AIDS Res Ther. 2013;10(1):32. https://doi.org/10.1186/1742-6405-10-32
11. Julian T, Rekatsina M, Shafique F, et al. Human immunodeficiency virus–related peripheral neuropathy: A systematic review and meta-analysis. Eur J Neurol. 2021;28(4):1420-31. https://doi.org/10.1111/ene.14656
12. Kazamel M, Stino AM, Smith AG. Metabolic syndrome and peripheral neuropathy. Muscle Nerve. 2021;63(3):285-93. https:// doi.org/10.1002/mus.27086
13. Biver E. Osteoporosis and HIV infection. Calcif Tissue Int 2022;110(5):624-40. https://doi.org/10.1007/s00223-022-00946-4
14. Delpino MV, Quarleri J. Influence of HIV infection and antiretroviral therapy on bone homeostasis. Front Endocrinol (Lausanne). 2020;11:502. Epub 20200902. https://doi.org/10.3389/fendo.2020.00502
15. Kamel NS, Gammack JK. Insomnia in the elderly: Cause, approach, and treatment. Am J Med. 2006;119(6):463-9. https://doi. org/10.1016/j.amjmed.2005.10.051
16. Omonuwa TS, Goforth HW, Preud’homme X, et al. The pharmacologic management of insomnia in patients with HIV. J Clin Sleep Med. 2009;05(03):251-62. https://doi.org/10.5664/jcsm.27496
17. Roth T. Insomnia: Definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007;3(5 suppl):S7-S10. https://doi. org/10.5664/jcsm.26929
18. Shahriar S, Araf Y, Ahmad R, et al. Insights into the coinfections of human immunodeficiency virus-hepatitis B virus, human immunodeficiency virus-hepatitis C virus, and hepatitis B virus-hepatitis C virus: Prevalence, risk factors, pathogenesis, diagnosis, and treatment Front Microbiol. 2022;12:780887. https://doi.org/10.3389/fmicb.2021.780887
19. Vivithanaporn P, Kongratanapasert T, Suriyapakorn B, et al. Potential drug-drug interactions of antiretrovirals and antimicrobials detected by three databases. Sci Rep. 2021;11(1):6089. https://doi.org/10.1038/s41598-021-85586-8
20. Suriyapakorn B, Chairat P, Boonyoprakarn S, et al. Comparison of potential drug-drug interactions with metabolic syndrome medications detected by two databases. PLoS One. 2019;14(11):e0225239. https://doi.org/10.1371/journal.pone.0225239
21. Thailand National List of Essential Medicines Bangkok, Thailand: National Drug System Development Comittee; 2021. p. 1-339.
22. stata.com. Kappa — Interrater agreement: Stata.com; 2022 [cited 2022 15 Jan 2023]. Available from: https://www.stata.com/ manuals/rkappa.pdf.
23. Dubé MP, Cadden JJ. Lipid metabolism in treated HIV infection. Best Pract Res Clin Endocrinol Metab. 2011;25(3):429-42. https://doi.org/10.1016/j.beem.2011.04.004
24. Giannarelli C, Klein RS, Badimon JJ. Cardiovascular implications of HIV-induced dyslipidemia. Atherosclerosis. 2011;219(2):384- 9. https://doi.org/10.1016/j.atherosclerosis.2011.06.003
25. Chauvin B, Drouot S, Barrail-Tran A, et al. Drug–drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors. Clin Pharmacokinet. 2013;52(10):815-31. https://doi.org/10.1007/s40262-013-0075-4
26. Maggi P, Di Biagio A, Rusconi S, et al. Cardiovascular risk and dyslipidemia among persons living with HIV: a review. BMC Infect Dis. 2017;17(1):551. https://doi.org/10.1186/s12879-017-2626-z
27. Chastain DB, Stover KR, Riche DM. Evidence-based review of statin use in patients with HIV on antiretroviral therapy. J Clin Transl Endocrinol. 2017;8:6-14. https://doi.org/10.1016/j.jcte.2017.01.004
28. Hirano M, Maeda K, Shitara Y, et al. Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006;34(7):1229. https://doi.org/10.1124/dmd.106.009290
29. Duncan AD, Goff LM, Peters BS. Type 2 diabetes prevalence and its risk factors in HIV: A cross-sectional study. PLOS ONE. 2018;13(3):e0194199. https://doi.org/10.1371/journal.pone.0194199
30. Health NIo. HIV and Diabetes: National Institutes of Health 2021 [cited 2022 17 Oct 2022]. Available from: https://hivinfo.nih. gov/understanding-hiv/fact-sheets/hiv-and-diabetes
31. Monroe AK, Glesby MJ, Brown TT. Diagnosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis. 2015;60(3):453-62. https://doi.org/10.1093/cid/ciu779
32. Kimura N, Masuda S, Tanihara Y, et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005;20(5):379-86. https://doi.org/10.2133/dmpk.20.379
33. Reese MJ, Savina PM, Generaux GT, et al. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013;41(2):353–61. https://doi.org/10.1124/dmd.112.048918
34. Song IH, Zong J, Borland J, et al. The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects. J Acquir Immune Defic Syndr. 2016;72(4):400-7. https://doi.org/10.1097/qai.0000000000000983
35. Naccarato M, Yoong D, Fong IW. Dolutegravir and metformin: a case of hyperlactatemia. AIDS. 2017;31(15):2176-7. https:// doi.org/10.1097/qad.0000000000001617
36. Cattaneo D, Resnati C, Rizzardini G, et al. Dolutegravir and metformin: a clinically relevant or just a pharmacokinetic interaction? AIDS. 2018;32(4):532-3. https://doi.org/10.1097/qad.0000000000001617
37. Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins). Clin Pharmacokinet 2010;49(9):573-88. https://doi. org/10.2165/11532980-000000000-00000
38. Triant VA. Cardiovascular disease and HIV infection. Curr HIV/AIDS Rep. 2013;10(3):199-206. https://doi.org/10.1007/s11904- 013-0168-6
39. Schwartz T, Maracantoni E, Allen N, et al. Platelet activity and platelet-induced endothelial inflammatory pathways in treated HIV is lowered by clopidogrel: a randomized control trial [abstract]. International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress; Philadelphia, PA2021.
40. Marsousi N, Daali Y, Fontana P, et al. Impact of boosted antiretroviral therapy on the pharmacokinetics and efficacy of clopidogrel and prasugrel active metabolites. Clin Pharmacokinet. 2018;57(10):1347-54. https://doi.org/10.1007/s40262-018-0637-6
41. Fravel MA, Ernst M. Drug interactions with antihypertensives. Curr Hypertens Rep. 2021;23(3):14. https://doi.org/10.1007/ s11906-021-01131-y
42. Harrison TB, Smith B. Neuromuscular manifestations of HIV/AIDS. J Clin Neuromuscul Dis. 2011;13(2):68-84. https://doi. org/10.1097/cnd.0b013e318221256f
43. Benevides MLACdSe, Filho SB, Debona R, et al. Prevalence of peripheral neuropathy and associated factors in HIV-infected patients. J Neurol Sci. 2017;375:316-20. https://doi.org/10.1016/j.jns.2017.02.011
44. Product information: ULTRAM(R) oral tablets, tramadol hydrochloride oral tablets. Raritan, NJ: Ortho-McNeil Pharmaceutical Inc; 2007.
45. Product Information: ULTRAM(R) ER oral extended-release tablets, tramadol HCl oral extended-release tablets. Titusville, NJ: Valeant Pharmaceuticals International Inc (per FDA); 2016.
46. Schütz SG, Robinson-Papp J. HIV-related neuropathy: Current perspectives. HIV AIDS (Auckl). 2013;5:243-51. Epub 20130911. https://doi.org/10.2147/HIV.S36674 PubMed PMID: 24049460; PubMed Central PMCID: PMC3775622.
47. Thompson A, Silverman B, Dzeng L, et al. Psychotropic medications and HIV. Clin Infect Dis. 2006;42(9):1305-10. https://doi. org/10.1086/501454
48. Bockbrader HN, Wesche D, Miller R, et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661-9. https://doi.org/10.2165/11536200-000000000-00000
49. Ramanathan S, Shen G, Hinkle J, et al. Pharmacokinetic evaluation of drug interactions with ritonavir-boosted HIV integrase inhibitor GS-9137 (elvitegravir) and acid-reducing agents. The Eighth International Workshop on Clinical Pharmacology of HIV Therapy; Budapest, Hungary. Utrecht, The Netherlands: Virology Education; 2007.
50. Kiser JJ, Bumpass JB, Meditz AL, et al. Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers. Antimicrob Agents Chemother. 2010;54(12):4999-5003. https://doi.org/10.1128/AAC.00636- 10
51. Song I, Borland J, Arya N, et al. Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. J Clin Pharmacol. 2015;55(5):490-6. https://doi.org/10.1002/jcph.439
52. Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis. 2015;60(8):1242-51. https://doi.org/10.1093/cid/civ010
53. Porras AG, Holland SD, Gertz BJ. Pharmacokinetics of alendronate. Clin Pharmacokinet. 1999;36(5):315-28. https://doi. org/10.2165/00003088-199936050-00002
54. Negredo E, Bonjoch A, Clotet B. Management of bone mineral density in HIV-infected patients. Expert Opin Pharmacother. 2016;17(6):845-52. https://doi.org/10.1517/14656566.2016.1146690
55. Hileman CO, Overton ET, McComsey GA. Vitamin D and bone loss in HIV. Curr Opin HIV AIDS. 2016;11(3):277–84. https://doi. org/10.1097/coh.0000000000000272
56. Kunisaki KM, De Francesco D, Sabin CA, et al. Sleep disorders in human immunodeficiency virus: A substudy of the pharmacokinetics and clinical observations in people over fifty (POPPY) study. Open Forum Infect Dis. 2021;8(1):ofaa561. https://doi.org/10.1093/ofid/ofaa561
57. Services USDoHH. Hepatitis B & C: U.S. Department of Health & Human Services; 2022 [cited 2022 17 Oct 2022]. Available from: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/other-related-health-issues/hepatitis-b-and-c#:~:text=HIV%20 and%20Hepatitis%20B%20and%20Hepatitis%20C%20Coinfection&text=Viral%20hepatitis%20progresses%20faster%20 and,deaths%20among%20people%20with%20HIV.
58. de Vries–Sluijs TEMS, Reijnders JGP, Hansen BE, et al. Long-term therapy with tenofovir is effective for patients co-infected with human immunodeficiency virus and hepatitis B virus. Gastroenterology. 2010;139(6):1934-41. https://doi.org/10.1053/j. gastro.2010.08.045
59. Matthews GV, Seaberg E, Dore GJ, et al. Combination HBV therapy is linked to greater HBV DNA suppression in a cohort of lamivudine-experienced HIV/HBV coinfected individuals. AIDS. 2009;23(13):1707-15. https://doi.org/10.1097/ QAD.0b013e32832b43f2
60. Patients with HIV/HCV coinfection: American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) [17 Oct 2022]. Available from: https://www.hcvguidelines.org/unique-populations/hiv-hcv.
61. Maughan A, Ogbuagu O. Pegylated interferon alpha 2a for the treatment of hepatitis C virus infection. Expert Opin Drug Metab Toxicol. 2018;14(2):219-27. https://doi.org/10.1080/17425255.2018.1421173
62. Smit C, Arends J, Peters L, et al. Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord. BMC Infect Dis. 2015;15(1):498. https://doi.org/10.1186/s12879-015-1224-1
63. Solas C, Pambrun E, Winnock M, et al. Ribavirin and abacavir drug interaction in HIV–HCV coinfected patients: fact or fiction? AIDS. 2012;26(17):2193-9. https://doi.org/10.1097/qad.0b013e32835763a4
64. Amorosa VK, Slim J, Mounzer K, et al. The influence of abacavir and other antiretroviral agents on virological response to HCV therapy among antiretroviral-treated HIV-infected patients. Antivir Ther. 2010;15(1):91-9. https://doi.org/10.3851/IMP1492
65. Pau AK. Clinical management of drug interaction with antiretroviral agents. Curr Opin HIV AIDS. 2008;3(3):319-24. https://doi. org/10.1097/COH.0b013e3282f82c06
66. Aronson JK. Classifying drug interactions. Br J Clin Pharmacol 2004;58(4):343-4. https://doi.org/0.1111/j.1365- 2125.2004.02244.x
67. Lewis LD. Drug–drug interactions: is there an optimal way to study them? Br J Clin Pharmacol. 2010;70(6):781-3. https://doi. org/10.1111/j.1365-2125.2010.03829.x

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