Background: Human Immunodeficiency Virus (HIV) is one of the main causes of morbidity and mortality; because of this it continues to be a major global public health concern. It has believed to kill more than 34 million lives so far. Sub Saharan Africa constitutes about 70% of people living with HIV among the 37 million on the globe. This region, accounted for more than two third of the global new HIV infections and about 15 million (40%) were receiving antiretroviral therapy (ART) at the end of 2014 throught the world. ART has fundamentally changed the treatment of HIV and transformed this infection from a disease of high mortality to chronic and medically managed disease. The issues of drug induced toxicities & complexity of current highly active antiretroviral therapy (HAART) regimens has remained of great concern. The aim of this study was to determine factors leading to antiretroviral regimen changes among HIV/AIDS Patients in the study area. Methods: A facility based retrospective cross-sectional study was conducted from April 28, 2017 to May 30, 2017 in the ART clinics of east and west Wollega zone health institutions using a pre-tested data collecting form and chart review. The sample included the 243 patients whose medication had been switched. Results: Majority 145 (59.67%) of the patients had been on ART for > 10 years duration. More than half 126(51.9%) of the patients had received tuberculosis (TB) treatment and almost three out of five patients (57.2%) had received isoniazid & cotrimoxazole prophylaxis. The most common reason for regimen change was peripheral neuropathy 146(60.1%) and the most common medication for this reason was stavudine, lamivudine and neverapine based 108(44.44%). Conclusions: The number of patients who changed ARV drug in our resource constrained setting present a challenge to the restricted treatment choices that we currently own. Less toxic and better-tolerated HIV treatment options should be available and used more frequently. Keywords: HIV/AIDS, HAART, ARV drug, Regimen change, Wollega * Correspondence: firstname.lastname@example.org Nekemte referral hospital, Nekemte, Ethiopia Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 2 of 8 Background enables recovery of the immune response and thereby Human immunodeficiency virus (HIV) annihilates and reduces risk of opportunistic infections (OIs) and compromises the function of immune cells. Immunity of death . infected individuals gradually depletes and susceptibility The decision to initiate ART for adults and adolescents to a wide range of infections and diseases would be depend on: WHO stage 3 and 4 disease irrespective of boosted. Acquired immunodeficiency syndrome (AIDS) CD4 cell count, CD4 count ≤500cells/mm irrespective is the most advanced stage of HIV infection, which can of WHO clinical stage and active tuberculosis (TB) take from 2 to 15 years to develop depending on the in- co-infection with HIV irrespective of CD4 cell count ac- dividual and it can be explained by the progression of cording to standard treatment guideline of Ethiopia . opportunistic infections, or other intense clinical mani- Triple combination therapy has been in use for more festations and certain cancers [1, 2]. than two decades globally. Currently, the preferred first HIV is one of the main causes of morbidity and mor- regimen triple therapy in Ethiopia consists of, two Nu- tality; because of this it continues to be a major global cleoside Reverse Transcriptase Inhibitors (NRTIs) and public health concern. It has believed to kill more than one Protease Inhibitor (PI) or a Non-Nucleoside Reverse 34 million lives so far. Sub Saharan Africa constitutes Transcriptase Inhibitor (NNRTI) or a triple therapy of about 70% of people living with HIV among the thirty three NRTIs. Based on the guideline, common ART reg- seven million on the globe. This region, accounted for imens in the country are; Tenofovir (TDF)/ Emtricita- more than two third of the global new HIV infections in bine (FTC)/ Efavirenz (EFV) or Nevirapine (NVP); 2014 with only 12% of the global population. Globally alternatives are TDF/ Lamivudine (3TC) /EFV or people receiving ART were about fifteen million (40%) NVP, Zidovudine (ZDV)/3TC/EFV or NVP. Other op- among those living with HIV of which about fourteen tions are Abacavir (ABC)/3TC/NVP, ABC/3TC/EFV million were in low- and middle –income countries and and ABC/3TC/ZDV. The second line regimen consists nearly one million were children . of ZDV ±3TC + Lopinavir/ritonavir (LPV/r) (or Ataza- Ethiopia is among the countries most affected by HIV/ navir/ritonavir (ATV/r)), ZDV + ABC + LPV/r (or AIDS with prevalence of 1.9% for women and 1.0% for ATV/r), TDF/3TC ± ZDV + LPV/r (or ATV/r), ABC/ men in 2011  and it is also in a low generalized HIV Didanosine (ddI) /LPV/r (or ATV/r), EFV or NVP / epidemic with significant heterogeneity among regions LPV/r (or ATV/r) [1, 9]. and population groups . The existence of HIV infec- Changes of multiple medications in HAART regimens tion in Ethiopia was recognized in the early 1980s with were commonly required simultaneously. These changes the first two AIDS cases reported in 1986. The predom- may be due to co morbidity with other chronic diseases, inant strain is HIV-1 subtype C, predominantly spread a desire for pregnancy, poor adherence, stock out of through unprotected heterosexual intercourse . Since drugs, treatment failure, long term toxicity or acute tox- 2000 the epidemic has declined  and recent figures icity. The approaches to change ART regimens depend show that HIV infection has significantly decreased over largely on amount of previous ART experience, available the years in the country . treatment options and reason for change. For example Highly active antiretroviral therapy (HAART) has fun- effective treatment can be accomplished by substituting damentally changed the treatment of HIV and changed another agent for the drug which has unpleasant effect this infection from a disease of high mortality to chronic in the regimen when it develops to certain drugs in the and medically managed disease which is a radical change regimen [7, 10]. in controlling the hardship of HIV/AIDS. However drug The issues of drug toxicities and complexity of current resistance and side effects were the great concern in HAART regimens has remained of great concern despite these advancements . Revolution in the care of pa- ARTs being of much help to the health of HIV/AIDS pa- tients with HIV/AIDS occurred due to the innovation of tients. Suboptimal therapy, discontinuation, and treat- potent HAART in around 2000. The qualities of life ment failure can be resulted from treatment toxicities of people living with HIV/AIDS (PLWHA) have im- and adherence problems . The consequence of proved and these treatments have dramatically re- these may complicate the management and lead to duced rates of mortality and morbidity among these toxicity, loss to follow-up, compromise the effective- patients. This result was also confirmed by World ness of HAART regimens, drug interactions and drug health organization (WHO) progress report. ARV resistance . drugs produce these effects by restoration of number Knowledge of the determinants of ART change may and quality of cluster of difference (CD4) cells and help to minimize the risk factors. These benefits in de- suppressing viral replication . creasing the rate of regimen change, treatment failure, The goal of ART is to attain maximal and durable drug resistance, and improve the quality of life of the pa- suppression of the viral replication. Viral suppression tient. Antiretroviral treatment change should be done Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 3 of 8 when necessary to spare the future treatment options. regimen change. The study was conducted from April The approach to patients who need to switch will differ 28, 2017 to May 30, 2017. depending on several issues, including ART experience and available options. Regimen substitution requires ad- Source and study population justment in learning the new medication about the treat- All HIV/AIDS positive patients who were greater than ment dosing, time of intake and deal with many 18 years and on HAART in east and west Wollega zone individual based inconveniences, which might be chal- health institutions ART Clinic from April 28, 2007 to lenging and reason for non-adherence [10, 13]. April 28, 2017 were the source population. All HIV/ Data on modification of HAART and factors associ- AIDS positive patients greater than 18 years who had ated with ARV drug regimen change are limited among undergone HAART regimen change in east and west HIV/AIDS patients in Ethiopia. Most of the surveys used Wollega zone health institutions ART Clinic in be- were on small sample of patients who were on ART for tween April 28, 2007 to April 28, 2017 were the study less than three years. As a result it is important to population. understand common reasons of ARV drug switch in pa- tients on long period exposure to ART. Inclusion and exclusion criteria Therefore, this study attempts to investigate the major Inclusion criteria: determinants of HAART regimen change among HIV/ AIDS patients in east and west Wollega zone health in- ✓ Patients on follow up in the ART clinic who had stitutions by using cross-sectional study. undergone HAART regimen change until the study period. ✓ Patients on follow up in the ART clinic who were on Objective second line regimen when the study was undergone. General objective ✓ HIV/AIDS patients who were greater than18 years. ✓ Patients receiving HAART regimen for at least ✓ To assess determinants of antiretroviral regimen 6 months at the beginning of the study period change among HIV/AIDS patients in east and west Wollega zone health institutions, Oromia region, west Exclusion criteria: Ethiopia. ✓ Patient information cards with incomplete Specific objectives information (Patient information card which had no one or more of information like information on ✓ To assess determinants of antiretroviral regimen demographics, WHO clinical stage, CD4 count, change among HIV/AIDS positive patients. initiation regimen and changed regimen, duration of ✓ To identify the pattern of initial ART regimens and initial therapy, and causes for regimen change). the subsequent changes. ✓ Patients with less than 6 months on HAART ✓ To assess the relationship between patient regimen. characteristics and reasons for initial ART change. ✓ Patients who didn’t switch HAART regimen. ✓ Under eighteen year old HIV/AIDS patients. Methods ✓ Deceased patients Study area, design, and period ✓ Transfer out patients The study was conducted in the ART clinics of east and west Wollega zone health institutions, Oromia region, Sample population west Ethiopia; Nekemte town which is the capital of east A total of 243 patients who had undergone HAART Wollega is located 328 km where as Gimbi town which regimen change in the ART clinics of east and west Wol- is the capital of west Wollega is 438 Km western to lega zone health institutions from April 28, 2007 to April Addis Ababa . 28, 2017 were included in the study while patients below The area is well known by its coffee production. The 18 years were excluded from the study. Patient informa- economy of the people is based on subsistence farming tion cards that showed a change in the initial treatment and livestock rearing. The climatic condition of the area regimen were assessed and analyzed, to identify the is ‘woinadega’ (semi-desert) and it is found at 2080 m common reasons that resulted in a change from the ini- above sea level. tial treatment regimen. A facility based retrospective cross-sectional study was conducted by reviewing patient information sheets and Study variables physician diagnostic cards to assess reasons for HAART Independent variables Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 4 of 8 ✓ Socio-demographic characteristics: age at initiation, Wollega University to zonal and woreda health offices of sex, marital status, educational status. east and west Wollega zone Administration to get per- ✓ Disease related variables: baseline WHO stage, base mission. After permission to conduct the study was ob- line CD4, and baseline weight. tained, data has been collected in one of refilling rooms ✓ ART related variables: types of initial regimen at ART Clinic by safe keeping of records. Only numerical identifications were used as a refer- Dependent variables ence, confidentiality and anonymity of subject was main- tained by not recording and identifying details, such as ✓ Reasons for change name or any other personal details. No disclosure of any name of the patients, the healthcare provider or drug Data procedure and management product was made in relation to the finding. Data collection procedure Data abstraction form was developed based on the ob- Operational definitions jectives of the study. It contained socio-demographic, ABC based regimen: regimen containing abacavir as clinical information and ART information such as, CD4 one of the NRTI backbones and may have different count, WHO stage, initial regimen, date on which treat- NNRI or PI bases. ment was started, date of ARV drug switch, duration of Antiretroviral drug switch/change: it is the change initial ARV therapy before first switch, regimen switched of one or two ARV drugs from the initial drug regimens. to, and causes for regimen change. The types of toxicity AZT based regimen: regimen containing zidovudine and treatment failure reasons were included. If there was as one of the NRTI backbones and may have different ARV drug switch for the second and third time it was NNRI or PI bases. recorded in a similar manner. For data collection four Table 1 Socio-demographic characteristics of HIV/AIDS patients 10th grade completed students were recruited. One who changed their HAART regimen in east and west Wollega pharmacist and one druggist from each health institu- zone health institutions, April 28, 2007 to April 28, 2017 tions were also recruited as supervisors. Demographic Characteristics N (%) Age in years Data collectors recruitment and training 20–34 19(7.8) Data collectors were recruited and trained methods of data collection prior to the start of actual data collection. 35–49 174(71.6) ≥ 50 50(20.6) Data quality assurance/control Sex Training was provided for supervisors and data collec- Female 127(52.3) tors and they were standardized. Data abstraction form Male 116(47.7) was pre-tested on randomly selected patient information Marital status cards to identify any drawbacks in Shambu hospital which is found in Horro Gudru Wollega zone before the Single 18(7.4) actual survey and improvements were made. The princi- Married 154(63.4) pal investigator supervised the data collection. Every Divorced 12(4.9) questionnaire was checked for completeness and logical Widowed 59(24.3) consistency. Educational status No formal education 74(30.5) Data processing and analysis The data were coded and entered in to a computer using Primary school education 92(37.9) statistical Package for the Social Sciences (SPSS) soft- Secondary school education 52(21.4) ware for windows version 20 and the analysis was per- Higher institute education 25(10.3) formed after the data were cleaned, edited and Family size processed. Distribution of Patients such as percentages Less than five 96(39.5) and their number by socio demographic characteristics 5–10 86(35.4) and other relevant variables in the study were described using descriptive analysis. > 10 61(25.1) Place of Residence Ethical considerations Urban 209(86) An official letter was written by department of phar- Rural 34(14) macy, college of public health and medical sciences, Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 5 of 8 Table 2 Clinical characteristics of HIV/AIDS patients who disturbances, CNS abnormalities or any other unwanted changed their HAART regimen in east and west Wollega zone effect related to HAART. health institutions, April 28, 2007 to April 28, 2017 Transfer out: Patients who changed their follow up to On initiation Before ART On data other health institution. of ART switch collection WHO clinical stage stage I 17 60 237 Results stage II 40 55 6 Socio-demographic characteristics of patients whose ART stage III 180 126 0 regimen changed stage IV 6 2 0 The mean age of patients was 43.68(SD ± 8.2) years. Ma- Total 243 243 243 jority of the patients 174(71.6%) were in the age range of 35–49 years and more than half 127(52.3%) of the pa- CD4 count (cells/ml) < 200 180 42 27 tients were females. About 154(63.4%) of the patients 200–350 60 54 26 were married. In this study only 77(31.7%) of the pa- > 350 03 147 190 tients received greater than secondary school education. Total 243 243 243 Regarding the family size 96(39.5%) of the patients had Weight (kg) < 45 51 24 24 < 5 family size whereas 61(25.1%) had > 10 family size. 45–60 164 155 137 Regarding place of residence 209(86%) were urban dwellers where as 34(14%) were rural dwellers as shown >60 28 64 82 in (Table 1). Total 243 243 243 Clinical characteristics of patients whose ART regimen Co morbidity: is defined as the occurrence of one or was changed more additional disorders which are on drug therapy During initiation of ART 180(74.1%) of the patients were on with HIV/AIDS simultaneously (TB, diabetes, WHO clinical stage III; whereas WHO stage after the ART hypertension). switch was stage I for 237(97.53%) of patients. Similarly more d4T based regimen: regimen containing Stavudine as than two third 180(74.1%) of patients had baseline CD4 one of the NRTI backbones and may have different count less than 200 cells/μLoninitiationbutmost NNRI or PI bases. 190(78.19%) of patients had > 350 cells/μLafter ART switch. TDF based regimen: regimen containing Tenofovir as In addition, the weight of the majority 164(67.5%) of patients one of the NRTI backbones and may have different during initiation of ART was between 45 and 60 kg (Table 2). NNRI or PI bases. Majority 145 (59.67%) of the patients had been on ART for Toxicity: is defined as the occurrence of adverse >10 years duration (Fig. 1). About 126(51.85%) of the pa- events such as diarrhea, nausea, vomiting, anemia, rash, tients had received TB treatment whereas 117(48.15%) of the fatigue, peripheral neuropathy, lipodystrophy, metabolic patients did not receive TB treatment. Regarding OI Fig. 1 Years of stay on ART of HIV/AIDS patients who changed their HAART regimen in east and west Wollega zone health institutions, April 28, 2007 to April 28, 2017 Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 6 of 8 Table 3 OI prophylaxis taken by study population in east and Table 5 Patterns of ART switch of HIV/AIDS patients who west Wollega zone health institutions, April 28, 2007 to April 28, changed their HAART regimen in east and west Wollega zone 2017 health institutions, April 28, 2007 to April 28, 2017 Type of OI prophylaxis Frequency Percent ART drugs after switching Frequency Percent Cotrimoxazole & Isoniazid 139 57.2 AZT + 3TC + NVP 47 19.3 Cotrimoxazole 95 39.1 AZT + 3TC + EFV 16 6.6 Neither 9 3.7 TDF + 3TC + EFV 56 23.05 Total 243 100.0 TDF + 3TC + NVP 98 40.33 ABC+ ddi + LPV/R 6 2.5 AZT + 3TC + ATV/R 6 2.5 prophylaxis 139(57.2%) of the patients received Cotrimoxa- zole and Isonazid prophylaxis (Table 3). TDF + 3TC + LPV/R 10 4.1 TDF + 3TC + ATV/R 4 1.6 Patterns of initial ART regimen and regimen switched to/ Total 243 100.0 changed regimen Majority of the patients 159(65.4%) started their initial ART health institutions which might have different co on D4t-3TC-NVP regimens, followed by D4t-3TC-EFV 55 morbidities. (22.6%). Only 12% of patients started initial ART regimen Majority of the study population 145 (59.67%) had on AZT based regimen (Table 4). been on ART for > 10 years. This finding indicated lon- The HAART regimen of majority of the patients ger duration as compared to other studies as all patients 168(69.14%) was changed to TDF based regimen. stayed on ART for less than 3 years in Bedelle  and Whereas about 69(28.4%) of the patients initial HAART in Addis Ababa about 98% of patients stayed on ART for regimen was changed to AZT based regimen and only less than one and half years and in Dessie only 6% pa- 6(2.5%) patients initial HAART regimen was changed to tients stayed on ART for more than 2 years [10, 16]. ABC based regimen (Table 5). The main reason for initial ARV drug switch in the present study was toxicity which was known as periph- Reasons for ART change eral neuropathy and it accounted for more than 60% of The main reason for antiretroviral regimen change was HAART regimen change. This finding was in agreement Peripheral neuropathy 146(60.1%) followed by hepatotox- with the study conducted in some parts of Ethiopia . icity, d4t faith out, CNS toxicity, Anemia, Rash etc. (Table The other reasons for HAART regimen change were 4). The most common reason for regimen change was hepatotoxicity 22(9.1%), anemia 16(6.6%) and rash15 peripheral neuropathy 146(60.1%) and the most common (5.3%). The combined sum of hepatotoxicity, anemia medication for this reason was stavudine, lamivudine and and peripheral neuropathy was more than 80%, which neverapine based 108(44.44%) (Table 6 and 7). was much higher than the studies done in United King- dom (35%)  and India (27%) . However, it was al- Discussion most similar to the studies conducted in other parts of The present retrospective cross sectional study of HIV/ Ethiopia as it was 75.8% in Mekelle  and 66% in Des- AIDS patients who changed their HAART regimen in sie . But there was a significant heterogeneity on the east and west Wollega zone health institutions described type of toxicities in these studies. the pattern of ART regimen and the common reasons for ARV drug switch. Such studies would be helpful in Table 6 Common reasons for modification of regimens of understanding the complexity of ART use of patients in study population in east and west Wollega zone health institutions, April 28, 2007 to April 28, 2017 Table 4 HAART regimen at initiation among HIV/AIDS patients Reason for regimen change Frequency Percent who changed their HAART regimen in east and west Wollega Peripheral neuropathy 146 60.1 zone health institutions, April 28, 2007 to April 28, 2017 Hepatotoxicity 22 9.1 Initial HAART regimen Frequency Percent D4t-3TC-NVP 159 65.4 d4t phase out 18 7.4 D4t-3TC-EFV 55 22.6 CNS toxicities 16 6.6 AZT-3TC-NVP 14 5.8 Anemia 16 6.6 AZT-3TC-EFV 15 6.2 Rash 15 5.3 Total 243 100.0 Others 10 4.9 Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 7 of 8 Table 7 Common reasons for modification by first treatment regimens among study population in east and west Wollega zone health institutions, April 28, 2007 to April 28, 2017 Patterns Reasons for ART regimen change Total of ART Regimen Anemia Rash Peripheral neuropathy Hepatotoxicity Diarrhea CNS stigma d4t phase jaundice Burning/ toxicities disclosure out numbness d4t-3TC-NVP 5 8 108 16 0 4 0 16 0 2 159 d4t-3TC-EFV 0 3 30 6 0 10 2 2 0 2 55 AZT-3TC-NVP 4 0 2 0 4 2 0 0 2 0 14 AZT-3TC-EFV 7 2 6 0 0 0 0 0 0 0 15 Total 16 13 146 22 4 16 2 18 2 4 243 Change of the entire regimen from first-line to resistance across the population to recommend future second-line is required in case of treatment failure. In therapy options. Therefore national and health institu- order to increase likelihood of treatment success and tion based surveillance of antiretroviral drug resistance minimize the risk of cross-resistance the new should be conducted. It helps to know the resistance second-line regimen should involve drugs that keep ac- pattern and select the locally effective treatments. Na- tivity against the patient’s virus strain and should prefer- tional level study on reasons for regimen change should ably include at least three new drugs, one or more from be done to help drug suppliers and policy makers to im- a new class . The preferred strategy for second-line prove and solve the problem. The reasons of ARV drug ART for adults is using a boosted PI and two NRTI switch observed in this cross sectional study should be combinations when NNRTI-containing regimens were investigated further in longitudinal multicenter studies used in first-line ART . Patients from low-income of ART utilization. countries were less likely to change two or more drugs Abbreviations and to change to a protease-inhibitor-containing regi- 3TC: Lamivudine; ABC: Abacavir; ART: Antiretro Viral Therapy; men when compared with patients from high-income ARV: Antiretroviral; ATV/R: Atazanavir/Ritonavir; AZT: Zidovudine; CD4: Cluster countries . of Difference; CNS: Central Nervous System; CYP: Cytochrome p-450; d4T: Stavudine; ddI: Didanosine; EFV: Efavirenz; FTC: Emitricibine; The study also found that there was high prevalence of HAART: Highly Active Antiretroviral Therapy; LPV/R: Lopinavir/Ritonavir; TB as almost three out of five patients (57%) had re- NNRTI: Nucleoside Reverse Transcriptase inhibitor; NRTI: Nucleoside Reverse ceived isoniazid & cotrimoxazole prophylaxis and more Transcriptase inhibitor; NVP: Nevirapine; OI: Opportunistic Infection; PI: Protease Inhibitors; PLWHA: People Living With HIV/AIDS; SD: Standard than half (52%) of the patients had been treated for TB deviation; TB : Tuberculosis; TDF: Tenofovir; VL: Viral Load; WHO: World [16, 19]. NVP has high interaction with Rifampicin Health Organization which is strong liver enzyme (CYP 3A4) inducer where by therapeutic level of NVP is decreased up to 40% Acknowledgments The authors would like to express their sincere gratitude to Wollega which necessitates switch to EFV. Additive hepatotox- University for their support for the accomplishment of this study. The icity effects also exists when NVP and Rifampicin were authors are also thankful for officials of east and west Wollega zone health used together according to findings of some studies offices for delivering necessary information for this study. We would also like to thank supervisors and data collectors for taking their precious time to which is another requirement to switch from NVP to collect the data. We are also thankful for staff members of ART clinics from EFV as the latter has lesser adverse drug reaction with which the data was collected. Rifampicin . Funding Conclusions No funding was obtained for this study. The number of patients who changed ARV drug in our Availability of data and materials resource constrained setting present a challenge to the All the necessary data were analyzed and included in this manuscript. restricted treatment choices that we currently own. The Further data may be obtained from the primary author upon request. main reasons for ART switch were toxicity among which Peripheral neuropathy and hepatotocity were the leading Authors’ contributions toxicity for ART switch. Less toxic and better-tolerated The authors’ responsibilities were as follows: AB designed and supervised the study, and ensured quality of the data and made a substantial contribution HIV treatment options should be available and used to the local implementation of the study assisted in the analysis and more frequently in east and west Wollega zone health interpretation of the data. BK participated in the design of the study, institutions. Patient should be evaluated regularly after a performed the data collection and the statistical analysis. GB also designed and supervised the study, and made a substantial contribution to the local treatment change to assess for potential concerns with implementation of the study. We want to ensure that all authors have the new regimen, medication tolerance and to assess the performed all important points specified on criteria and guidelines for effectiveness. Information is needed on patterns of authorship and all authors read and approved the final manuscript. Bokore et al. BMC Pharmacology and Toxicology (2018) 19:28 Page 8 of 8 Authors’ information 12. Hendrickson S, Jacobson P, Nelson W, et al. Host genetic influences on AB is graduated from Jimma University with bachelor of pharmacy, from highly active antiretroviral therapy efficacy and AIDS free survival. J Acquire Unity University with bachelor of arts degree in economics and from Immune Deficient Syndrome. 2008;48(3):263–71. Wollega University with masters of public health and has published many 13. Demessie R, Mekonnen A, Amogne W, et al. Knowledge and adherence to original research articles in an international journals, is currently working at antiretroviral therapy among adult people living with HIV / AIDS at Nekemte referral hospital chronic care pharmacy, P.O. Box 25, Nekemte, TikurAnbessa specialized hospital, Ethiopia. International Journal of Basic & Ethiopia. BK is graduated from Wollega University with bachelor of Clinical Pharmacology. 2014;3(2):320–30. pharmacy, is currently working at Nekemte referral hospital chronic care 14. Nekemte town health Office (NTHO) Census 2009. pharmacy, P.O. Box 25, Nekemte, Ethiopia. GB has also published many 15. Mekonnen Y, Molla G. Reason for regimen change among HIV patients on original research articles in an international journals, is currently a lecturer at initial highly active antiretroviral therapy in Bedele. Journal of Biotechnology Wollega University College of health and medical sciences, department of and Bio safety. 2014;2(4):116–22. pharmacy, P.O. Box 395, Nekemte, Ethiopia. 16. Mulugeta A, Chane T. Causes of antiretroviral drug changes among patients on antiretroviral therapy. Int J Pharm Sci Res. 2012;3(1):120–5. 17. Messou E, Anglaret X, Duvignac J, et al. Antiretroviral treatment changes in Ethics approval and consent to participate adults from Côte d’Ivoire: the roles of tuberculosis and pregnancy. AIDS The study was approved by the ethical review committee of Wollega (London, England). 2010;24(1):93–9. University. Official letter from the University explaining the aim of the study 18. Sandeep B, Vansant C, Raghunandan M, et al. Factors influencing the was submitted to zonal and woreda health offices of east and west Wollega substitution of antiretroviral therapy in human immunodeficiency virus/ zone and support of the administration was obtained prior to pursuing the acquired immunodeficiency syndrome patients on first line highly active study. Informed written consent was obtained from the study participants antiretroviral therapy. Asian Journal of Pharmaceutical and Clinical Research. before data collection and clinical review of patients which was already 2014;7(5):117–20. recorded was used; confidentiality and anonymity of subject was maintained 19. Bayou T, Woldu M, Gebre Meskel G, et al. Factors determinant for change of by not recording and identifying details, such as name or any other personal initial antiretroviral treatment regimen among patients on ART follow-up identifiers. No disclosure of any name of the patients, the healthcare clinic of Mekelle hospital, Mekelle, Ethiopia. International Journal of Basic & provider or drug product was made in relation to the finding. Only Clinical Pharmacology. 2014;3(1):44. numerical identifications were used as a reference. All data forms were 20. Zhou J, Kumarasamy N, Boyd M, et al. Deferred modification of antiretroviral stored in a confidential and secure place. regimen following documented treatment failure in Asia: Results from the TREAT Asia HIV Observational Database (TAHOD). HIV Medicine. 2010;11(1): Competing interests 31–9. The authors declare that they have no competing interests. 21. Hawkins C, Achenbach C, Fryda W, et al. Antiretroviral durability and tolerability in HIV-infected adults living in urban Kenya. J Acquir Immune Defic Syndr. 2009;45(3):304–10. Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1 2 Nekemte referral hospital, Nekemte, Ethiopia. Wollega University, Nekemte, Ethiopia. Received: 15 September 2017 Accepted: 31 May 2018 References 1. Food, Medicine and Health Care Administration and Control Authority (FMHACA); Standard Treatment Guidelines for general hospitals; 3rd edition; Addis Ababa. Ethiopia 2014. 2. World Health organization (WHO); Fact Sheet; 2015. 3. Central Statistical Agency Ethiopia and ICF International. Ethiopia demographic and health survey. Addis Ababa, Ethiopia and Calverton, Maryland: Central Statistical Agency and ICF International; 2012. 4. World Health Organization (WHO). HIV/AIDS Progress in 2014; Update Ethiopia, WHO country office for Ethiopia UNECA compound; Addis Ababa, Ethiopia; March 2015. 5. Federal democratic republic of Ethiopia. Country progress reports on HIV/ AIDS; Addis Ababa, Ethiopia; 2012. 6. Federal Ministry of Health (MOH). Health Sector Development Program IV: (2010/11–2014/15), Final draft. Addis Ababa, Ethiopia: MOH. p. 2010. 7. Wilkin T, Marshall G, Gulick M. Switching antiretroviral therapy why, when and how. J Acquir Immune Defic Syndr. 2010;12:782–9. 8. World Health organization (WHO). Global update on HIV treatment: results, impact and opportunities, brief summary. Kuala Lumpur, Malaysia: WHO; 2013a. 9. Federal Ministry of Health (MOH). Guideline for implantation of the antiretroviral therapy program in Ethiopia. Addis Ababa, Ethiopia: MOH; 10. Jima T, Angamo M, Wabe N. Causes for antiretroviral regimen change among HIV/AIDS patients in Addis Ababa. Ethiopia Tanzania Journal of Health Research. 2013;15(1):1–9. 11. Park B, Choe G, Kim H, et al. Early modification of initial HAART regimen associated with poor clinical outcome in HIV patients. AIDS Res Hum Retrovir. 2010;23(8):794–800.
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