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Adverse Drug Reactions and Clinical Outcomes in Patients Initiated on Antiretroviral Therapy: A Prospective Cohort Study From Ethiopia

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Abstract

Introduction

In Ethiopia, the use of antiretroviral therapy (ART) has been scaled up for HIV/AIDS over the past decade. Adverse drug reactions (ADRs) associated with ART pose a unique challenge in the treatment of the infection in this resource-limited setting.

Objectives

The aims of this study were to examine the incidence and nature of ADRs, identify the risk factors associated with the development of ADRs, and assess their impact on treatment outcomes.

Methods

A prospective cohort study was conducted in adult patients (≥18 years of age) with HIV/AIDS who commenced ART. All ADRs in the first 12 months of therapy were recorded, and the severity, causality, and preventability assessed. The impact of severe ADRs on self-reported adherence, immunological, and body mass index (BMI) outcomes were assessed.

Results

Of the 211 patients included in the analysis, 181 (85.7 %) experienced at least one ADR and 66 (31.3 %) experienced at least one severe ADR within 12 months of commencing ART (incidence rates for any ADR and severe ADR of 14.8 and 3.2 per 100 person-months, respectively). Logistic regression analysis indicated that taking zidovudine-containing regimens (odds ratio [OR] 4.2, 95 % confidence interval [CI] 2.1–8.4) or being unemployed (OR 2.2, 95 % CI 1.1–4.3) were independent predictors of experiencing severe ADRs. Patients who experienced a severe ADR were less likely (OR 0.4, 95 % CI 0.2–0.9) to be ≥90 % adherent to ART. The mean gain in BMI was significantly lower in patients with severe ADRs after 3 and 12 months of therapy.

Conclusions

ADRs were common within the first 3 months in patients initiated on ART. Severe ADRs were negatively associated with self-reported adherence and gain in BMI. Measures need to be implemented to routinely monitor for severe ADRs to improve ART adherence and treatment outcomes.

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References

  1. World Health Organization. Global update on HIV treatment: results, impacts and opportunities. 2013. Available at: http://www.who.int/hiv/data/global treatment report presentation. Accessed 20 Mar 2013.

  2. Michaels SH, Clark R, Kissinger P. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;339(6):405–6.

    Article  CAS  PubMed  Google Scholar 

  3. Ammassari A, Murri R, Pezzotti P, Trotta MP, Ravasio L, De Longis P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr. 2001;28(5):445–9.

    Article  CAS  PubMed  Google Scholar 

  4. Shubber Z, Calmy A, Andrieux-Meyer I, Vitoria M, Renaud-Thery F, Shaffer N, et al. Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis. AIDS. 2013;27(9):1403–12.

    Article  CAS  PubMed  Google Scholar 

  5. Cespedes MS, Aberg JA. Neuropsychiatric complications of antiretroviral therapy. Drug Saf. 2006;29(10):865–74.

    Article  CAS  PubMed  Google Scholar 

  6. Sagwa E, Ruswa N, Musasa JP, Mantel-Teeuwisse AK. Adverse events during treatment of drug-resistant tuberculosis: a comparison between patients with or without human immunodeficiency virus co-infection. Drug Saf. 2013;36(11):1087–96.

    Article  CAS  PubMed  Google Scholar 

  7. Ethiopian Federal Ministry of Health HIV/AIDS Prevention and Control Office. Multi-sectoral HIV/AIDS response monitoring and evaluation report. 2011. Available at: http://www.etharc.org/resources. Accessed 13 July 2012.

  8. Reniers G, Araya T, Davey G, Nagelkerke N, Berhane Y, Coutinho R, et al. Steep declines in population-level AIDS mortality following the introduction of antiretroviral therapy in Addis Ababa, Ethiopia. AIDS. 2009;23(4):511–8.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Ethiopian Federal Ministry of Health HIV/ AIDS Prevention and Control office (HAPCO). Country progress report in HIV/AIDS response. Addis Ababa: Ethiopian Federal Ministry of Health HIV/ AIDS Prevention and Control office. 2012. Available at: http://www.unaids.org. Accessed 13 Mar 2013.

  10. Abdissa SG, Fekade D, Feleke Y, Seboxa T, Diro E. Adverse drug reactions associated with antiretroviral treatment among adult Ethiopian patients in a tertiary hospital. Ethiop Med J. 2012;50(2):107–13.

    PubMed  Google Scholar 

  11. Tadesse WT, Mekonnen AB, Hailu W, Tadesse YT. Self-reported adverse drug reactions and their influence on highly active antiretroviral therapy in HIV infected patients: a cross sectional study. BMC Pharmacol Toxicol. 2014;15(1):32.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Fowler MG, Owor M. Monitoring HIV treatment in resource-limited settings: reassuring news on the usefulness of CD4(+) cell counts. J Infect Dis. 2009;199(9):1255–7.

    Article  PubMed  Google Scholar 

  13. Bezabhe WM, Peterson GM, Bereznicki L, Chalmers L, Gee P. Adherence to antiretroviral drug therapy in adult patients who are HIV-positive in Northwest Ethiopia: a study protocol. BMJ Open. 2013;3(10):e003559.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Ethiopian Federal Ministry of Health HIV/ AIDS Prevention and Control Office (HAPCO). Guidelines for management of opportunistic infections and antiretroviral treatment in adolescents and adults in Ethiopia. 2008. Available at: http://www.who.int/hiv/pub/guidelines/ethiopia_art.pdf. Accessed 24 Mar 2015.

  15. World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach 2010 revision. 2010. Available at: http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf. Accessed 2 Apr 2015.

  16. Edwards IR, Biriell C. Harmonisation in pharmacovigilance. Drug Saf. 1994;10(2):93–102.

    Article  CAS  PubMed  Google Scholar 

  17. National Institute of Allergy and Infectious Diseases. Division of AIDS table for grading the severity of adult and paediatric adverse events (DAIDS AE Grading Table). December 2004, with clarification published on August 2009. Available at: http://rsc.tech-res.com/Document/safetyandpharmacovigilance/Tableforgradingseverityofadultpediatricadverseevents.pdf. Accessed 29 Mar 2012.

  18. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts E, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45.

    Article  CAS  PubMed  Google Scholar 

  19. Schumock GT, Thornton JP. Focusing on the preventability of adverse drug reactions. Hosp Pharm. 1992;27(6):538.

    CAS  PubMed  Google Scholar 

  20. Grabar S, Le Moing V, Goujard C, Leport C, Kazatchkine MD, Costagliola D, et al. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med. 2000;133(6):401–10.

    Article  CAS  PubMed  Google Scholar 

  21. Chesney MA, Ickovics JR, Chambers DB, Gifford AL, Neidig J, Zwickl B, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. Patient Care Committee and Adherence Working Group of the Outcomes Committee of the Adult AIDS Clinical Trials Group (AACTG). AIDS Care. 2000;12(3):255–66.

    Article  CAS  PubMed  Google Scholar 

  22. Meresse M, March L, Kouanfack C, Bonono RC, Boyer S, Laborde-Balen G, et al. Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon. HIV Med. 2014;15(8):478–87.

    Article  CAS  PubMed  Google Scholar 

  23. Sethi AK, Celentano DD, Gange SJ, Moore RD, Gallant JE. Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance. Clin Infect Dis. 2003;37(8):1112–8.

    Article  PubMed  Google Scholar 

  24. Khalili H, Dashti-Khavidaki S, Mohraz M, Etghani A, Almasi F. Antiretroviral induced adverse drug reactions in Iranian human immunodeficiency virus positive patients. Pharmacoepidemiol Drug Saf. 2009;18(9):848–57.

    Article  CAS  PubMed  Google Scholar 

  25. Shet A, Antony J, Arumugam K, Kumar Dodderi S, Rodrigues R, DeCosta A. Influence of adverse drug reactions on treatment success: prospective cohort analysis of HIV-infected individuals initiating first-line antiretroviral therapy in India. PloS One. 2014;9(3):e91028.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Rudorf DC, Krikorian SA. Adverse effects associated with antiretroviral therapy and potential management strategies. J Pharm Pract. 2005;18(4):258–77.

    Article  Google Scholar 

  27. Reginald OO, Haruna MM, Sani GB, Eric T-A, Adebola OT, Mathew I, et al. Adverse reactions associated with antiretroviral regimens in adult patients of a university teaching Hospital HIV Program in Zaria, Northern Nigeria: an observational cohort study. J Antivir Antiretrovir. 2012;4(1):6–13.

    Article  Google Scholar 

  28. Cooper CL, Breau C, Laroche A, Lee C, Garber G. Clinical outcomes of first antiretroviral regimen in HIV/hepatitis C virus co-infection. HIV Med. 2006;7(1):32–7.

    Article  CAS  PubMed  Google Scholar 

  29. Eluwa GI, Badru T, Akpoigbe KJ. Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria. BMC Clin Pharmacol. 2012;12:7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Severe P, Leger P, Charles M, Noel F, Bonhomme G, Bois G, et al. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med. 2005;353(22):2325–34.

    Article  CAS  PubMed  Google Scholar 

  31. Modayil RR, Harugeri A, Parthasarathi G, Ramesh M, Prasad R, Naik V, et al. Adverse drug reactions to antiretroviral therapy (ART): an experience of spontaneous reporting and intensive monitoring from ART centre in India. Pharmacoepidemiol Drug Saf. 2010;19(3):247–55.

    Article  CAS  PubMed  Google Scholar 

  32. Bezabhe WM, Chalmers L, Bereznicki LR, Peterson GM, Bimirew MA, Kassie DM. Barriers and facilitators of adherence to antiretroviral drug therapy and retention in care among adult HIV-positive patients: a qualitative study from Ethiopia. PloS One. 2014;9(5):e97353.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Jena A, Sachdeva RK, Sharma A, Wanchu A. Adverse drug reactions to nonnucleoside reverse transcriptase inhibitor-based antiretroviral regimen: a 24-week prospective study. J Int Assoc Physicians AIDS Care (Chic). 2009;8(5):318–22.

    Article  Google Scholar 

  34. Nagpal M, Tayal V, Kumar S, Gupta U. Adverse drug reactions to antiretroviral therapy in AIDS patients at a tertiary care hospital in India: a prospective observational study. Indian J Med Sci. 2010;64(6):245–52.

    Article  PubMed  Google Scholar 

  35. Kumarasamy N, Venkatesh KK, Cecelia AJ, Devaleenal B, Lai AR, Saghayam S, et al. Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients. AIDS Patient Care STDS. 2008;22(4):337–44.

    Article  CAS  PubMed  Google Scholar 

  36. Clark R. Sex differences in antiretroviral therapy-associated intolerance and adverse events. Drug Saf. 2005;28(12):1075–83.

    Article  CAS  PubMed  Google Scholar 

  37. Bersoff-Matcha SJ, Miller WC, Aberg JA, van Der Horst C, Hamrick HJ Jr, Powderly WG, et al. Sex differences in nevirapine rash. Clin Infect Dis. 2001;32(1):124–9.

    Article  CAS  PubMed  Google Scholar 

  38. Omer HM, Hodson J, Thomas SK, Coleman JJ. Multiple drug intolerance syndrome: a large-scale retrospective study. Drug Saf. 2014;37(12):1037–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. d’Arminio Monforte A, Lepri AC, Rezza G, Pezzotti P, Antinori A, Phillips AN, et al. Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naive Patients. AIDS. 2000;14(5):499–507.

    Article  PubMed  Google Scholar 

  40. von Wyl V, Klimkait T, Yerly S, Nicca D, Furrer H, Cavassini M, et al. Adherence as a predictor of the development of class-specific resistance mutations: the Swiss HIV Cohort Study. PloS One. 2013;8(10):e77691.

    Article  Google Scholar 

  41. Simpson K, Chen SY, Wu A, Boulanger L, Chambers R, Nedrow K, et al. Costs of adverse events among patients with HIV infection treated with nonnucleoside reverse transcriptase inhibitors. HIV Med. 2014;15(8):488–98.

    Article  CAS  PubMed  Google Scholar 

  42. Weiser SD, Tuller DM, Frongillo EA, Senkungu J, Mukiibi N, Bangsberg DR. Food insecurity as a barrier to sustained antiretroviral therapy adherence in Uganda. PloS One. 2010;5(4):e10340.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Fox MP, Rosen S, MacLeod WB, Wasunna M, Bii M, Foglia G, et al. The impact of HIV/AIDS on labour productivity in Kenya. Trop Med Int Health. 2004;9(3):318–24.

    Article  PubMed  Google Scholar 

  44. Reisler RB, Han C, Burman WJ, Tedaldi EM, Neaton JD. Grade 4 events are as important as AIDS events in the era of HAART. J Acquir Immune Defic Syndr. 2003;34(4):379–86.

    Article  PubMed  Google Scholar 

  45. Stone VE, Hogan JW, Schuman P, Rompalo AM, Howard AA, Korkontzelou C, et al. Antiretroviral regimen complexity, self-reported adherence, and HIV patients’ understanding of their regimens: survey of women in the her study. J Acquir Immune Defic Syndr. 2001;28(2):124–31.

    Article  CAS  PubMed  Google Scholar 

  46. Gurwitz JH, Field TS, Avorn J, McCormick D, Jain S, Eckler M, et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med. 2000;109(2):87–94.

    Article  CAS  PubMed  Google Scholar 

  47. Messou E, Gabillard D, Moh R, Inwoley A, Sorho S, Eholie S, et al. Anthropometric and immunological success of antiretroviral therapy and prediction of virological success in west African adults. Bull World Health Organ. 2008;86(6):435–42.

    PubMed Central  PubMed  Google Scholar 

  48. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach (2013). Report No.: 978 92 4 1505727. Available at: http://www.who.int/hiv/pub/guidelines. Accessed 3 July 2014.

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Funding

This study was financially supported by the Division of Pharmacy, School of Medicine, University of Tasmania, Hobart, TAS, Australia.

Conflict of interest

Woldesellassie M. Bezabhe, Luke R. Bereznicki, Leanne Chalmers, Peter Gee, Desalew M. Kassie, Mekides A. Bimirew, and Gregory M. Peterson have no conflicts of interest to declare that are directly relevant to the content of this study. Gregory M. Peterson is the principal investigator in the Ethiopian HIV Evaluation (EHIVE) Project.

Acknowledgments

The authors are grateful to Mr. Adane Minayehu, Mr. Zemene Demelash, and Mr. Dawit Demelash who worked as research pharmacists. We are also grateful to the study participants who volunteered for this study, and healthcare providers in the ART clinics who assisted in the recruitment process.

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Authors and Affiliations

  1. Division of Pharmacy, School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia

    Woldesellassie M. Bezabhe, Luke R. Bereznicki, Leanne Chalmers, Peter Gee & Gregory M. Peterson

  2. College of Medicine and Health Science, Bahir-Dar University, Gojjam, Ethiopia

    Woldesellassie M. Bezabhe

  3. Department of Internal Medicine, Gondar University Hospital, Gondar, Ethiopia

    Desalew M. Kassie

  4. Department of Internal Medicine, Felege-Hiwot Hospital, Gojjam, Ethiopia

    Mekides A. Bimirew

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  1. Woldesellassie M. Bezabhe
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Correspondence to Woldesellassie M. Bezabhe.

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Bezabhe, W.M., Bereznicki, L.R., Chalmers, L. et al. Adverse Drug Reactions and Clinical Outcomes in Patients Initiated on Antiretroviral Therapy: A Prospective Cohort Study From Ethiopia. Drug Saf 38, 629–639 (2015). https://doi.org/10.1007/s40264-015-0295-7

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