Pill Burden: A Major Barrier to HAART Adherence and Fixed Dose Combinations (FDCS) as its Solution A Mini-Review
- Authors: Simon M.1, Derrick S.1, Kosanam S.2, Pasupula R.1
-
Affiliations:
- Department. of Pharmacology, College of Pharmacy, Koneru Lakshmaiah Education Foundation, KL Deemed to be University
- Department of Pharmacy Practice, Sandip Institute of Pharmaceutical Sciences
- Issue: Vol 22, No 3 (2024)
- Pages: 143-152
- Section: Medicine
- URL: https://rjpbr.com/1570-162X/article/view/644064
- DOI: https://doi.org/10.2174/011570162X307740240604115154
- ID: 644064
Cite item
Full Text
Abstract
:HIV/ AIDS is a global pandemic, one of the most challenging; with no cure for the disease, various therapies available in the form of regimens as Highly Active Anti-Retroviral Therapy (HAART) or simply Anti-Retroviral Therapy (ART) are the only way to manage the disease. The Fixed Dose Combinations (FDCs) concept has been a well-recognised improvement in pharmacotherapy for the treatment of a variety of chronic maladies like hypertension, diabetes, HIV/AIDS, and several FDC products consisting of HIV drugs are approved. These single-tablet regimens have been essential in streamlining ART, lowering pill burden and increasing adherence. Adherence to HAART is the most vital factor to ensure medication success and virologic suppression. However, adherence is faced with several barriers including adverse effects of drugs, the complexity of ART, social-cultural factors, and pill burden among others. This writing reviews the concept of adherence to ART, and its barriers while stressing pill burden as a significant one which we suggest would be solved by using Fixed Dose Combinations (FDCs).
About the authors
Mugisa Simon
Department. of Pharmacology, College of Pharmacy, Koneru Lakshmaiah Education Foundation, KL Deemed to be University
Email: info@benthamscience.net
Ssebaduka Derrick
Department. of Pharmacology, College of Pharmacy, Koneru Lakshmaiah Education Foundation, KL Deemed to be University
Email: info@benthamscience.net
Sreya Kosanam
Department of Pharmacy Practice, Sandip Institute of Pharmaceutical Sciences
Email: info@benthamscience.net
Rajeshwari Pasupula
Department. of Pharmacology, College of Pharmacy, Koneru Lakshmaiah Education Foundation, KL Deemed to be University
Author for correspondence.
Email: info@benthamscience.net
References
- Larmarange J, Bendaud V. HIV estimates at second subnational level from national population-based surveys. AIDS 2014; 28(4) (Suppl. 4): S469-76. doi: 10.1097/QAD.0000000000000480 PMID: 25406750
- Gazzard BG, Anderson J, Babiker A, et al. British HIV Association guidelines for the treatment of HIV‐1‐infected adults with antiretroviral therapy 2008. HIV Med 2008; 9(8): 563-608. doi: 10.1111/j.1468-1293.2008.00636.x PMID: 18826546
- Iacob SA, Iacob DG, Jugulete G. Improving the adherence to antiretroviral therapy, a difficult but essential task for a successful hiv treatmentclinical points of view and practical considerations. Front Pharmacol 2017; 8: 831. doi: 10.3389/fphar.2017.00831 PMID: 29218008
- Spaulding A, Rutherford GW, Siegfried N. Tenofovir or zidovudine in three-drug combination therapy with one nucleoside reverse transcriptase inhibitor and one non-nucleoside reverse transcriptase inhibitor for initial treatment of HIV infection in antiretroviral-naïve individuals. Cochrane Libr 2010; (10): CD008740. doi: 10.1002/14651858.CD008740 PMID: 20927777
- Buscher A, Hartman C, Kallen MA, Giordano TP. Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naïve HIV patients. Int J STD AIDS 2012; 23(5): 351-5. doi: 10.1258/ijsa.2011.011292 PMID: 22648890
- Everson F, Genis A, Ogundipe T, et al. Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats. PLoS One 2018; 13(12): e0208537. doi: 10.1371/journal.pone.0208537 PMID: 30517206
- Lu DY, Wu HY, Yarla NS, Xu B, Ding J, Lu TR. HAART in HIV/AIDS treatments: Future trends. Infect Disord Drug Targets 2018; 18(1): 15-22. doi: 10.2174/1871526517666170505122800 PMID: 28474549
- Zhang J, Vernon K, Li Q, et al. Single-agent and fixed-dose combination HIV-1 protease inhibitor drugs in fission yeast (Schizosaccharomyces pombe). Pathogens 2021; 10(7): 804. doi: 10.3390/pathogens10070804 PMID: 34202872
- Reda AA, Biadgilign S. Determinants of adherence to antiretroviral therapy among HIV-infected patients in Africa. Aids Res Treat 2012; 2012: 1-8. doi: 10.1155/2012/574656 PMID: 22461980
- McCool J, Dobson R, Whittaker R, Paton C. Mobile health (mHealth) in low- and middle-income countries. Annu Rev Public Health 2022; 43(1): 525-39. doi: 10.1146/annurev-publhealth-052620-093850 PMID: 34648368
- Hodes R, Cluver L, Toska E, Vale B. Pesky metrics: The challenges of measuring ART adherence among HIV-positive adolescents in South Africa. Crit Public Health 2020; 30(2): 179-90. doi: 10.1080/09581596.2018.1550253
- McComsey GA, Lingohr-Smith M, Rogers R, Lin J, Donga P. Real-world adherence to antiretroviral therapy among HIV-1 patients across the United States. Adv Ther 2021; 38(9): 4961-74. doi: 10.1007/s12325-021-01883-8 PMID: 34390465
- Myers LB, Midence K. Concepts and Issues in Adherence Adherence to Treatment in Medical Conditions. CRC Press 1998.
- Nachega JB, Mills EJ, Schechter M. Antiretroviral therapy adherence and retention in care in middle-income and low-income countries: Current status of knowledge and research priorities. Curr Opin HIV AIDS 2010; 5(1): 70-7. doi: 10.1097/COH.0b013e328333ad61 PMID: 20046150
- Godman B, McCabe H, D Leong T, et al. Fixed dose drug combinations are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries. Expert Rev Pharmacoecon Outcomes Res 2020; 20(1): 1-26. doi: 10.1080/14737167.2020.1734456 PMID: 32237953
- de los Rios P, Okoli C, Punekar Y, et al. Prevalence, determinants, and impact of suboptimal adherence to HIV medication in 25 countries. Prev Med 2020; 139: 106182. doi: 10.1016/j.ypmed.2020.106182 PMID: 32593732
- Juday T, Gupta S, Grimm K, Wagner S, Kim E. Factors associated with complete adherence to HIV combination antiretroviral therapy. HIV Clin Trials 2011; 12(2): 71-8. doi: 10.1310/hct1202-71 PMID: 21498150
- Hudelson C, Cluver L. Factors associated with adherence to antiretroviral therapy among adolescents living with HIV/AIDS in low- and middle-income countries: A systematic review. AIDS Care 2015; 27(7): 805-16. doi: 10.1080/09540121.2015.1011073 PMID: 25702789
- Ankrah D, Koster E, Mantel-Teeuwisse A, Arhinful D, Agyepong I, Lartey M. Facilitators and barriers to antiretroviral therapy adherence among adolescents in Ghana. Patient Prefer Adherence 2016; 10: 329-37. doi: 10.2147/PPA.S96691 PMID: 27042024
- Pefura-Yone EW, Soh E, Kengne AP, Balkissou AD, Kuaban C. Non-adherence to antiretroviral therapy in Yaounde: Prevalence, determinants and the concordance of two screening criteria. J Infect Public Health 2013; 6(4): 307-15. doi: 10.1016/j.jiph.2013.02.003 PMID: 23806707
- Arts EJ, Hazuda DJ. HIV-1 antiretroviral drug therapy. Cold Spring Harb Perspect Med 2012; 2(4): a007161. doi: 10.1101/cshperspect.a007161 PMID: 22474613
- Landovitz RJ, Scott H, Deeks SG. Prevention, treatment and cure of HIV infection. Nat Rev Microbiol 2023; 21(10): 657-70. doi: 10.1038/s41579-023-00914-1 PMID: 37344551
- Atta MG, De Seigneux S, Lucas GM. Clinical pharmacology in HIV therapy. Clin J Am Soc Nephrol 2019; 14(3): 435-44. doi: 10.2215/CJN.02240218 PMID: 29844056
- Ramdas P, Sahu AK, Mishra T, Bhardwaj V, Chande A. From entry to egress: Strategic exploitation of the cellular processes by HIV-1. Front Microbiol 2020; 11: 559792. doi: 10.3389/fmicb.2020.559792 PMID: 33343516
- Aquaro S, Borrajo A, Pellegrino M, Svicher V. Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages. Virulence 2020; 11(1): 400-13. doi: 10.1080/21505594.2020.1760443 PMID: 32375558
- Nash D, Tymejczyk O, Gadisa T, et al. Factors associated with initiation of antiretroviral therapy in the advanced stages of HIV infection in six Ethiopian HIV clinics, 2012 to 2013. J Int AIDS Soc 2016; 19(1): 20637. doi: 10.7448/IAS.19.1.20637 PMID: 27113335
- Initiation of antiretroviral therapy. ARV Guidel 2019 Available from: https://arv.guidelines.org.au/adult/initiation-therapy/ (accessed 17 Apr 2024).
- Eriksen J, Carlander C, Albert J, et al. Antiretroviral treatment for HIV infection: Swedish recommendations 2019. Infect Dis 2020; 52(5): 295-329. doi: 10.1080/23744235.2019.1707867 PMID: 31928282
- Gandhi RT, Bedimo R, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults. JAMA 2023; 329(1): 63-84. doi: 10.1001/jama.2022.22246 PMID: 36454551
- Ryom L, Cotter A, De Miguel R, et al. 2019 update of the European AIDS clinical society guidelines for treatment of people living with HIV version 10.0. HIV Med 2020; 21(10): 617-24. doi: 10.1111/hiv.12878 PMID: 32885559
- EACS Guidelines. EACS Guidel 2023. Available from: https://eacs.sanfordguide.com
- Krentz HB, Campbell S, Lahl M, Gill MJ. De‐simplifying single‐tablet antiretroviral treatments: Uptake, risks and cost savings. HIV Med 2019; 20(3): 214-21. doi: 10.1111/hiv.12701 PMID: 30632660
- Smith SJ, Zhao XZ, Passos DO, Lyumkis D, Burke TR Jr, Hughes SH. Integrase strand transfer inhibitors are effective Anti-HIV drugs. Viruses 2021; 13(2): 205. doi: 10.3390/v13020205 PMID: 33572956
- Scarsi KK, Havens JP, Podany AT, Avedissian SN, Fletcher CV. HIV-1 integrase inhibitors: A comparative review of efficacy and safety. Drugs 2020; 80(16): 1649-76. doi: 10.1007/s40265-020-01379-9 PMID: 32860583
- Deeks ED. Doravirine: First global approval. Drugs 2018; 78(15): 1643-50. doi: 10.1007/s40265-018-0993-4 PMID: 30341683
- De Clercq E. Tenofovir at the crossroad of the therapy and prophylaxis of HIV and HBV infections. J Cell Immunol 2020; 2(1): 23-30. doi: 10.33696/immunology.2.015
- Velvanathan T, Islahudin F, Sim BL, Taha NA. Simplification of HAART therapy on ambulatory HIV patients in Malaysia: A randomized controlled trial. Pharm Pract 2016; 14(4): 830. doi: 10.18549/PharmPract.2016.04.830 PMID: 28042354
- Murri R, Antinori A, Ammassari A, et al. Physician estimates of adherence and the patient-physician relationship as a setting to improve adherence to antiretroviral therapy. J Acquir Immune Defic Syndr 2002; 31(31) (Suppl. 3): S158-62. doi: 10.1097/00126334-200212153-00015 PMID: 12562042
- Powell-Cope GM, White J, Henkelman EJ, Turner BJ. Qualitative and quantitative assessments of HAART adherence of substance-abusing women. AIDS Care 2003; 15(2): 239-49. doi: 10.1080/0954012031000068380 PMID: 12856345
- Vink NM, Klungel OH, Stolk RP, Denig P. Comparison of various measures for assessing medication refill adherence using prescription data. Pharmacoepidemiol Drug Saf 2009; 18(2): 159-65. doi: 10.1002/pds.1698 PMID: 19109809
- Monforte AA, Lepri AC, Rezza G, et al. Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. AIDS 2000; 14(5): 499-507. doi: 10.1097/00002030-200003310-00005 PMID: 10780712
- Elzi L, Erb S, Furrer H, et al. Adverse events of raltegravir and dolutegravir. AIDS 2017; 31(13): 1853-8. doi: 10.1097/QAD.0000000000001590 PMID: 28692533
- Oyugi JH, Byakika-Tusiime J, Ragland K, et al. Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda. AIDS 2007; 21(8): 965-71. doi: 10.1097/QAD.0b013e32802e6bfa PMID: 17457090
- Tao X, Lu Y, Zhou Y, Zhang L, Chen Y. Efficacy and safety of the regimens containing tenofovir alafenamide versus tenofovir disoproxil fumarate in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection: A meta-analysis of randomized controlled trials. Int J Infect Dis 2020; 93: 108-17. doi: 10.1016/j.ijid.2020.01.035 PMID: 31988012
- Esser S, Helbig D, Hillen U, Dissemond J, Grabbe S. Side effects of HIV therapy. J Dtsch Dermatol Ges 2007; 5(9): 745-54. doi: 10.1111/j.1610-0387.2007.06322.x PMID: 17760894
- Rotunda A, Rotunda A, Rotunda A, Rotunda A. Severe cutaneous reactions associated with the use of human immunodeficiency virus medications. Acta Derm Venereol 2003; 83(1): 1-9. doi: 10.1080/00015550310002611 PMID: 12636014
- Gong Y, Haque S, Chowdhury P, et al. Pharmacokinetics and pharmacodynamics of cytochrome P450 inhibitors for HIV treatment. Expert Opin Drug Metab Toxicol 2019; 15(5): 417-27. doi: 10.1080/17425255.2019.1604685 PMID: 30951643
- Nascimento ALCS, Fernandes RP, Quijia C, et al. Pharmacokinetic parameters of HIV‐1 protease inhibitors. ChemMedChem 2020; 15(12): 1018-29. doi: 10.1002/cmdc.202000101 PMID: 32390304
- Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12(7): F51-8. doi: 10.1097/00002030-199807000-00003 PMID: 9619798
- Brooks KM, George JM, Kumar P. Drug interactions in HIV treatment: Complementary & alternative medicines and over-the-counter products. Expert Rev Clin Pharmacol 2017; 10(1): 59-79. doi: 10.1080/17512433.2017.1246180 PMID: 27715369
- Stuardo Ávila V, Manriquez Urbina JM, Fajreldin Chuaqui V, Belmar Prieto J, Valenzuela Santibáñez V. Model of socio-cultural dimensions involved in adherence to antiretroviral therapy for HIV/AIDS in public health care centers in Chile. AIDS Care 2016; 28(11): 1441-7. doi: 10.1080/09540121.2016.1179252 PMID: 27144342
- Abaasa AM, Todd J, Ekoru K, et al. Good adherence to HAART and improved survival in a community HIV/AIDS treatment and care programme: The experience of The AIDS Support Organization (TASO), Kampala, Uganda. BMC Health Serv Res 2008; 8(1): 241. doi: 10.1186/1472-6963-8-241 PMID: 19021908
- Airoldi M, Zaccarelli M, Bisi L, et al. One-pill once-a-day HAART: A simplification strategy that improves adherence and quality of life of HIV-infected subjects. Patient Prefer Adherence 2010; 4: 115-25. PMID: 20517472
- Arya DS, Chowdhury S, Chawla R, et al. Clinical benefits of fixed dose combinations translated to improved patient compliance. J Assoc Physicians India 2019; 67(12): 58-64. PMID: 31801333
- DeJesus E, Young B, Morales-Ramirez JO, et al. Simplification of antiretroviral therapy to a single-tablet regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate versus unmodified antiretroviral therapy in virologically suppressed HIV-1-infected patients. J Acquir Immune Defic Syndr 2009; 51(2): 163-74. doi: 10.1097/QAI.0b013e3181a572cf PMID: 19357529
- Pujari SN, Patel AK, Naik E, et al. Effectiveness of generic fixed-dose combinations of highly active antiretroviral therapy for treatment of HIV infection in India. J Acquir Immune Defic Syndr 2004; 37(5): 1566-9. doi: 10.1097/00126334-200412150-00005 PMID: 15577409
- Parczewski M, Witak-Jędra M. Clinical data and practical experience related to Stribild as an option in patients with HIV infection. HIV AIDS Rev 2015; 14(4): 104-8. doi: 10.1016/j.hivar.2015.03.002
- Murrell DE, Moorman JP, Harirforoosh S. Stribild: A review of component characteristics and combination drug efficacy. ETSU Fac Works 2015; 19(5): 904-14. PMID: 25807445
- Mills AM, Cohen C, DeJesus E, et al. Efficacy and safety 48 weeks after switching from efavirenz to rilpivirine using emtricitabine/tenofovir disoproxil fumarate-based single-tablet regimens. HIV Clin Trials 2013; 14(5): 216-23. doi: 10.1310/hct1405-216 PMID: 24144898
- DeJesus E, Ramgopal M, Crofoot G, et al. Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: A randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV 2017; 4(5): e205-13. doi: 10.1016/S2352-3018(17)30032-2 PMID: 28259776
- Choudhary MC, Mellors JW. The transformation of HIV therapy: One pill once a day. Antivir Ther 2022; 27(2) doi: 10.1177/13596535211062396 PMID: 35492017
- Bunn HT, Hester EK, Maldonado RA, Childress D. Evaluation of human immunodeficiency virus medication errors in a community hospital following the implementation of a pharmacist‐led antiretroviral stewardship program. J Am Coll Clin Pharm 2020; 3(3): 593-600. doi: 10.1002/jac5.1196
- Rolle CP, Berhe M, Singh T, et al. Dolutegravir/lamivudine as a first-line regimen in a test-and-treat setting for newly diagnosed people living with HIV. AIDS 2021; 35(12): 1957-65. doi: 10.1097/QAD.0000000000002979 PMID: 34115650
- Graham SM, Grzemska M, Gie RP. The background and rationale for a new fixed-dose combination for first-line treatment of tuberculosis in children. Int J Tuberc Lung Dis 2015; 19(12) (Suppl. 1): 3-8. doi: 10.5588/ijtld.15.0416 PMID: 26564534
- Vitoria M, Vella S, Ford N. Scaling up antiretroviral therapy in resource-limited settings. Curr Opin HIV AIDS 2013; 8(1): 12-8. doi: 10.1097/COH.0b013e32835b8123 PMID: 23188179
- Ligade VS, Thakar TM, Dengale SJ. Fixed dose combinations of anti‐tubercular, antimalarial and antiretroviral medicines on the Indian market: Critical analysis of ubiquity, sales and regulatory status. Trop Med Int Health 2019; 24(2): 238-46. doi: 10.1111/tmi.13180 PMID: 30422371
- Waning B, Kyle M, Diedrichsen E, et al. Intervening in global markets to improve access to HIV/AIDS treatment: an analysis of international policies and the dynamics of global antiretroviral medicines markets. Global Health 2010; 6(1): 9. doi: 10.1186/1744-8603-6-9 PMID: 20500827
- Sax PE, Meyers JL, Mugavero M, Davis KL. Adherence to antiretroviral treatment and correlation with risk of hospitalization among commercially insured HIV patients in the United States. PLoS One 2012; 7(2): e31591. doi: 10.1371/journal.pone.0031591 PMID: 22384040
- Scott Sutton S, Magagnoli J, Hardin JW. Impact of pill burden on adherence, risk of hospitalization, and viral suppression in patients with HIV infection and AIDS receiving antiretroviral therapy. Pharmacotherapy 2016; 36(4): 385-401. doi: 10.1002/phar.1728 PMID: 26923931
- Freije I, Lamouche S, Tanguay M. Review of drugs approved via the 505(b)(2) pathway: Uncovering drug development trends and regulatory requirements. Ther Innov Regul Sci 2020; 54(1): 128-38. doi: 10.1007/s43441-019-00036-y PMID: 32008242
- Shehu-Xhilaga M, Tachedjian G, Crowe S, Kedzierska K. Antiretroviral compounds: Mechanisms underlying failure of HAART to eradicate HIV-1. Curr Med Chem 2005; 12(15): 1705-19. doi: 10.2174/0929867054367211 PMID: 16029143
- Marzolini C, Elzi L, Gibbons S, et al. Prevalence of comedications and effect of potential drugdrug interactions in the swiss HIV cohort study. Antivir Ther 2010; 15(3): 413-23. doi: 10.3851/IMP1540 PMID: 20516560
- Ebrahim O, Mazanderani AH. Recent developments in HIV treatment and their dissemination in poor countries. Infect Dis Rep 2013; 5(11) (Suppl. 1): e2. doi: 10.4081/idr.2013.s1.e2 PMID: 24470966
- Miranda MRH, Dubey A, G S R, Charyulu RN. Fixed-dose combinations banned in India: Is it the right decision? An eye-opening review. Expert Opin Drug Saf 2019; 18(10): 977-85. doi: 10.1080/14740338.2019.1651292 PMID: 31374180
- Auwal F, Dahiru MN, Abdu-Aguye SN. Availability and rationality of fixed dose combinations available in Kaduna, Nigeria. Pharm Pract 2019; 17(2): 1470. doi: 10.18549/PharmPract.2019.2.1470 PMID: 31275504
- Dalal K, Ganguly B, Gor A. Assessment of rationality of fixed dose combinations approved in CDSCO list. J Clin Diagn Res 2016; 10(4): FC05-8. doi: 10.7860/JCDR/2016/17856.7691 PMID: 27190825
- Mitra A, Wu Y. Challenges and opportunities in achieving bioequivalence for fixed-dose combination products. AAPS J 2012; 14(3): 646-55. doi: 10.1208/s12248-012-9378-x PMID: 22684403
- Llibre JM, Arribas JR, Domingo P, et al. Clinical implications of fixed-dose coformulations of antiretrovirals on the outcome of HIV-1 therapy. AIDS 2011; 25(14): 1683-90. doi: 10.1097/QAD.0b013e3283499cd9 PMID: 21673556
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