Sayan Kumar Das, Smita Shenoy, Muralidhar Varma, R Rajesh, Ravi Shankar, Sadhana Holla, Kavitha Saravu
Sayan Kumar Das1*, Smita Shenoy2, Muralidhar Varma3, R Rajesh4, Ravi Shankar5, Sadhana Holla6, Kavitha Saravu7
1Department of Pharmacology, All India Institute of Medical Sciences, Saket Nagar, Bhopal – 462020 (MP).
2Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka.
3Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka.
4Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka.
5Department of Biostatistics, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi.
6Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka.
7Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Centre for Infectious Diseases (MAC ID), Manipal Academy of Higher Education, Manip
Volume - 15,
Issue - 5,
Year - 2022
The high prevalence of comorbid conditions, both communicable and non-communicable, in HIV patients dictate the need for prescription of additional medications which makes way for the possibility of a particular medication altering the intensity of the pharmacotherapeutic effect of a concomitantly administered medication, a potential drug-drug interaction (PDDI), which can lead to the precipitation of adverse effects and even treatment failure. In this retrospective observational study, data was collected from medical records of adult HIV positive patients on antiretroviral therapy (ART) with comorbidities who visited the hospital between January, 2015 and June, 2017. Using the University of Liverpool drug-interaction database, the identified interactions were classified into three categories. The category of PDDI requiring monitoring, dose adjustment or adjustment of time of dosing was taken and evaluated for the type of interaction, risk and prevalence. Time of onset and severity was determined using Micromedex drug-interaction database. Data analysis was done using descriptive statistics and binomial logistic regression was used for risk estimation. In this study, a total of 244 people were enrolled. A total of 711 PDDIs were identified. By analysing risk ratio, patients with more than 5 concomitant medications, protease inhibitor-based ART regimen, duration of illness (=6 years), cardiovascular disease and presence of coinfections were at a higher risk of development of PDDIs. Pharmacokinetic PDDIs (87.2%) were higher in comparison to pharmacodynamic PDDIs (12.8%). Awareness among prescribers of this silent but important occurrence will help in recognition, prevention and management of PDDI which might otherwise complicate the therapeutic outcome.
Cite this article:
Sayan Kumar Das, Smita Shenoy, Muralidhar Varma, R Rajesh, Ravi Shankar, Sadhana Holla, Kavitha Saravu. A Study of Potential drug-drug interactions in HIV positive individuals with Co-morbidities. Research Journal of Pharmacy and Technology. 2022; 15(5):1960-6. doi: 10.52711/0974-360X.2022.00326
Sayan Kumar Das, Smita Shenoy, Muralidhar Varma, R Rajesh, Ravi Shankar, Sadhana Holla, Kavitha Saravu. A Study of Potential drug-drug interactions in HIV positive individuals with Co-morbidities. Research Journal of Pharmacy and Technology. 2022; 15(5):1960-6. doi: 10.52711/0974-360X.2022.00326 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2022-15-5-8
1. Fettig J, Swaminathan M, Murrill CS, Kaplan JE. Global epidemiology of HIV. Infectious Disease Clinics. 2014 Sep 1;28(3):323-37. doi: 10.1016/j.idc.2014.05.001
2. National AIDS Control Organisation (NACO). India HIV Estimations 2017, Technical Report. 2017. 2017. Available on: http://naco.gov.in/sites/default/files/HIV%20Estimations%202017%20Report_1.pdf
3. National AIDS Control Organisation (NACO). National AIDS Control Programme IV (NACP). 2019. Available on: http://naco.gov.in/nacp
4. World Health Organisation (WHO). The use of retroviral drugs for treating and preventing HIV infection 2016. 2016. Available on: https:// apps.who.in t/iris/ bitstream/ 10665/ 208825/1/9789241549684_en.pdf?ua=1
5. Siefried KJ, Mao L, Cysique LA, et al. Concomitant medication polypharmacy, interactions and imperfect adherence are common in Australian adults on suppressive antiretroviral therapy. AIDS (London, England). 2018 Jan 2;32(1):35. doi: 10.1097/QAD.0000000000001685
6. Scondotto G, Pojero F, Addario SP et al. The impact of polypharmacy and drug interactions among the elderly population in Western Sicily, Italy. Aging clinical and experimental research. 2018 Jan;30(1):81-7. doi.org/10.1007/s40520-017-0755-2
7. Hisaka A, Ohno Y, Yamamoto T, Suzuki H. Prediction of pharmacokinetic drug–drug interaction caused by changes in cytochrome P450 activity using in vivo information. Pharmacology & therapeutics. 2010 Feb 1;125(2):230-48. doi.org/10.1016/j.pharmthera.2009.10.011
8. Watkins CC, Pieper AA, Treisman GJ. Safety considerations in drug treatment of depression in HIV-positive patients. Drug safety. 2011 Aug;34(8):623-39. doi.org/10.2165/11592070-000000000-00000
9. Siddiqua A, Abdullah RK, Kareem NA. Impact of Clinical Pharmacist Intervention towards Polypharmacy in Elderly population-A Systematic Study. Research Journal of Pharmacy and Technology. 2019;12(6):2621-7. doi: 10.5958/0974-360X.2019.00439.6
10. Vidya V Gawande, AV Chandewar. Polypharmacy: An Overview. Research J. Pharm. and Tech. 4 (1): January 2011; Page 155-159. Available on: https://rjptonline.org/AbstractView.aspx?PID=2011-4-1-23
11. Abubakar AR, Simbak NB, Haque M. Adverse drug reactions: predisposing factors, modern classifications and causality assessment. Research Journal of Pharmacy and Technology. 2014;7(9):1091-8. doi: 10.5958/0974-360X available on: https://rjptonline.org/AbstractView.aspx?PID=2014-7-9-18
12. Archana B. Chavhan, Dipali M. Bhoi. Pharmacovigillance: Drug Safety Monitoring. Asian J. Pharm. Tech. 2019; 9(1):49-52. doi: 10.5958/2231-5713.2019.00009.6 available on: https://ajptonline.com/AbstractView.aspx?PID=2019-9-1-9
13. Rajeswari C, Selvi S. Anti-Retro Viral Therapy (ART) Adherence and Factors affecting Adherence among People living with HIV (PLHIVs). Asian Journal of Nursing Education and Research. 2017;7(3):337-40. doi: 10.5958/2349-2996.2017.00067.2
14. Rajesh R, Vidyasagar S, Varma DM, et al. A prospective study of highly active antiretroviral therapy in Indian human immunodeficiency virus positive patients. International journal of risk & safety in medicine. 2013 Jan 1;25(1):53-65. doi: 10.3233/JRS-130580
15. The University of Liverpool. HIV drug interactions. 2018. Available on: http://www.hiv-druginteractions.org.
16. IBM Watson Health, Greenwood Village, Colorado, USA. IBM Micromedex® Drug Interaction Checking (electronic version). 2018. Available on: https:// www. micromedexsolutions.com/
17. Zhao X, Lynch Jr JG, Chen Q. Reconsidering Baron and Kenny: Myths and truths about mediation analysis. Journal of consumer research. 2010 Aug 1;37(2):197-206. doi.org/10.1086/652283
18. Tseng A, Szadkowski L, Walmsley S, et al. Association of age with polypharmacy and risk of drug interactions with antiretroviral medications in HIV-positive patients. Annals of Pharmacotherapy. 2013 Nov;47(11):1429-39. doi.org/10.1177/1060028013504075
19. Wu L, Li X. Community-based HIV/AIDS interventions to promote psychosocial well-being among people living with HIV/AIDS: a literature review. Health Psychology and Behavioral Medicine: An Open Access Journal. 2013 Jan 1;1(1):31-46. doi.org/10.1155/2014/576592
20. Rathbun RC, Liedtke MD. Antiretroviral drug interactions: overview of interactions involving new and investigational agents and the role of therapeutic drug monitoring for management. Pharmaceutics. 2011 Dec;3(4):745-81. doi.org/10.3390/pharmaceutics3040745
21. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2018. Available on: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/
22. Moore HN, Mao L, Oramasionwu CU. Factors associated with polypharmacy and the prescription of multiple medications among persons living with HIV (PLWH) compared to non-PLWH. AIDS care. 2015 Dec 2;27(12):1443-8. doi.org/10.1080/09540121.2015.1109583
23. Sembian N. Polypharmacy and its Management. Research J. Pharm. and Tech. 7(3): Mar., 2014; Page 335-339. doi: 10.5958/0974-360X Available on: https://rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2014-7-3-16
24. Weinberg JL, Kovarik CL. The WHO clinical staging system for HIV/AIDS. AMA Journal of Ethics. 2010 Mar 1;12(3):202-6. doi: 10.1001/virtualmentor.2010.12.3.cprl1-1003
25. Mok S, Minson Q. Drug-related problems in hospitalized patients with HIV infection. American Journal of Health-System Pharmacy. 2008 Jan 1;65(1):55-9. doi.org/10.2146/ajhp070011
26. Hsue PY, Lo JC, Franklin A et al. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation. 2004 Apr 6;109(13):1603-8. doi.org/10.1161/01.CIR.0000124480.32233.8A
27. Glesby MJ et al. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clinical Pharmacology & Therapeutics. 2005 Aug;78(2):143-53. doi.org/10.1016/j.clpt.2005.04.005
28. Faragon JJ, Patel N. Cardiovascular and HIV Drug Interactions. InCardiovascular Care in Patients With HIV 2019 (pp. 209-224). Springer, Cham. doi: 10.1007/978-3-030-10451-1_15
29. Bristol-Myers Squibb Canada. Reyataz (atazanavir) [Product monograph]. 2013. Available on: https://www.bms.com/assets/bms/ca/documents/productmonograph/REYATAZ_EN_PM.pdf
30. Puech R, Gagnieu MC, Planus C et al. Extreme bradycardia due to multiple drug–drug interactions in a patient with HIV post-exposure prophylaxis containing lopinavir–ritonavir. British journal of clinical pharmacology. 2011 Apr;71(4):621. doi: 10.1111/j.1365-2125.2010.03849.x
31. Nachega JB, Hsu AJ, Uthman OA et al. Antiretroviral therapy adherence and drug–drug interactions in the aging HIV population. Aids. 2012 Jul 31;26:S39-53. doi: 10.1097/QAD.0b013e32835584ea
32. Capeau J, Bouteloup V, Katlama C et al. Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. Aids. 2012 Jan 28;26(3):303-14. doi: 10.1097/QAD.0b013e32834e8776
33. Gayathri V, Sharmila J, Navyatha N et al. Assessment of Drug Utilization pattern on Cardiovascular patients at a Tertiary Care Hospital in South India. Research Journal of Pharmacy and Technology. 2019;12(8):3781-6. doi.org/10.5958/0974-360X.2019.00647.4
34. Niemi M, Cascorbi I, Timm R et al. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clinical Pharmacology & Therapeutics. 2002 Sep;72(3):326-32. doi.org/10.1067/mcp.2002.127495
35. Scaria C, Satheesh A, Prabhakar P et al. Evaluation of Adverse Drug Reactions and their Management in Psychiatric in-Patients. Research Journal of Pharmacy and Technology. 2019;12(7):3455-61. doi: 10.5958/0974-360X.2019.00585.7
36. Abbott Laboratories. NORVIR (R) (ritonavir) tablets and oral solution. Prescribing information. 2017. Available on: https://www.rxabbvie.com/pdf/norvirtab_pi.pdf
37. Pham PA, Flexner C. Emerging antiretroviral drug interactions. Journal of Antimicrobial Chemotherapy. 2011 Feb 1;66(2):235-9. doi.org/10.1093/jac/dkq448
38. Piscitelli SC, Gallicano KD. Interactions among drugs for HIV and opportunistic infections. New England Journal of Medicine. 2001 Mar 29;344(13):984-96. doi: 10.1056/NEJM200103293441307
39. Redfearn DP, Trim GM, Skanes AC et al. Esophageal temperature monitoring during radiofrequency ablation of atrial fibrillation. Journal of cardiovascular electrophysiology. 2005 Jun;16(6):589-93. doi.org/10.1111/j.1469-0691.2004.00758.x
40. Bates M, Marais BJ, Zumla A. Tuberculosis comorbidity with communicable and noncommunicable diseases. Cold Spring Harbor perspectives in medicine. 2015 Nov 1;5(11):a017889. doi: 10.1101/cshperspect.a017889
41. Ku SW, Jiamsakul A, Joshi K et al. Cotrimoxazole prophylaxis decreases tuberculosis risk among Asian patients with HIV. Journal of the International AIDS Society. 2019 Mar;22(3):e25264. doi.org/10.1002/jia2.25264
42. Chijioke-Nwauche I. Malaria/HIV interactions in Nigeria-A review. Nigerian Health Journal. 2014;14(3):97-107. Available on: https://www.ajol.info/index.php/nhj/article/view/133214
43. Priyanka PS, Varma DM, Immadisetti K et al. Recognition of possible risk factors for clinically significant drug-drug interactions among Indian people living with HIV receiving highly active antiretroviral therapy and concomitant medications. International Journal of Risk & Safety in Medicine. 2017 Jan 1;29(1-2):25-55. doi: 10.3233/JRS-170738
44. Cruciol-Souza JM, Thomson JC. A pharmacoepidemiologic study of drug interactions in a Brazilian teaching hospital. Clinics. 2006;61:515-20. doi.org/10.1590/S1807-59322006000600005
45. Roberts JS, Watrous ML, Schulz RM et al. Quantifying the Clinical Significance of Drug—Drug Interactions: Scaling Pharmacists' Perceptions of a Common Interaction Classification Scheme. Annals of Pharmacotherapy. 1996 Sep;30(9):926-34. doi.org/10.1177/106002809603000902
46. Shoukath U, Khatoon F, Mahveen S, Uddin MN. Iatrogenic Disease. Asian Journal of Pharmaceutical Research. 2018;8(2):113-6. doi: 10.5958/2231-5691.2018.00020.5
47. Jose C, Antony M, Kumar JG et al. Conceptual and Practical Update on Drug-Drug Interactions. Research Journal of Pharmacy and Technology. 2016;9(1):60. doi:10.5958/0974-360X.2016.00011.1