Adherence to Dolutegravir-Based Antiretroviral Therapy and Its Associated Factors Among Children Living With HIV in Bahir Dar City Administration Public Health Institutions,North West Ethiopia

Abstract

Introduction. Optimal adherence is required for the better treatment outcome from highly active antiretroviral therapy. Though evidence-based regimen changes are being applied incessantly, adherence to those regimens should also be continuously monitored. Objectives. To assess the adherence and its determinants toward dolutegravir-based antiretroviral therapy among children in ART clinics in Bahir Dar City, Ethiopia. Methods. Institutional-based cross-sectional study was conducted from March 01 to April 31, 2023. Results. In this study, 71% of the respondents were on TDF+3TC+DTG-based regimen. The adherence level was found to be 90%. Children’s age (AOR = 3.877 [95% CI: 1.130, 13.291]), HIV-serostatus disclosure (AOR = 3.96 [95% CI: 1.43, 10.916]), CD4 counts (AOR = 3 [95% CI: 1.483, 6.069]), and comorbid illnesses (AOR = 0.3 [95% CI: 0.132, 0.707]) were determinant factors. Conclusions. In this study, the level of adherence to dolutegravir-based antiretroviral therapy was found to be higher with age, disclosure status, CD4 count, and comorbid illness being significant determinants for the adherence.

Keywords

adherence Bahir Dar children dolutegravir HAART

Introduction

According to the epidemiology of HIV Infection surveillance in Amhara region, the overall incidence rate of HIV from 2015 to 2018 was 6.9 per 1000 population. The annual HIV incidence rate was 7.3, 6.3, 7.4, and 6.63 per 100 populations in 2015, 2016, 2017, and 2018, respectively.¹ According to the research finding the incidence rate per 100 population was high in Dessie town (5.74), Bahir Dar City (4.27), and Gondar town (3.00). Ethiopia has made substantial progress in controlling the HIV/AIDS epidemic, with a 59% reduction in new infections and a 52% decrease in HIV-related deaths by 2022 compared to 2010.² However, HIV prevalence continues to be notably higher in urban areas, where it is estimated at 3%, compared to a national average of less than 1%. This highlights the ongoing challenges in controlling the epidemic, especially in more densely populated urban centers like Bahir Dar. Antiretroviral therapy (ART) is a treatment against human immune virus (HIV) which is a combination of various antiretroviral drugs. It should be taken continuously throughout life in order to prolong and improve the quality of life for persons with HIV by lowering viral loads and raising CD4 cell counts.¹ Adherence is the extent to which patients take medications as prescribed by their clinicians. The most important factor in the success of HIV treatment is adherence to ART.²

It has been demonstrated that a 10% higher level of adherence results in 21% reduction in disease progression. With 95% drug adherence level, viral suppression will become undetectable in 80% of the clients. However, a fall in drug adherence to 70% rapidly decreases viral suppression success rate to 33%.³ Sustainable and optimal adherence to treatment are key components in determining the success of highly active anti-retro viral therapy (HAART).⁴ ART non-adherence was found to be a major cause of virological failure and the emergence of HIV drug resistance (HIVDR). Good adherence to ART lowers incidence rates of HIV transmission as well as HIV-related fatalities.⁵ It is common for children to adhere to treatment regimens poorly in both developed and developing nations. For optimal virologic suppression, it is advised that patients take >95% of their prescribed doses which reduces their risk of virological failure by more than 50% and lowers treatment failure rates.⁶ Furthermore, parents may have a poor understanding of the need to take the medication and they may be unwilling to disclose the child’s HIV-positive status to the child or others involved in the clients’ care. This may create problems in administering doses while the parent is at work or the child at school. HIV develops resistance if the concentration of drugs in the blood is low. Hence, optimal adherence to ART is essential to ensure high serum level of drugs by taking medication correctly and consistently.⁷

Dolutegravir (DTG) is a medication used by people with a retroviral infection (RVI). This drug works better, simpler to take, and has less adverse effects than similar medications that are currently available. It is effective and started replacing non-nucleoside reverse transcriptase inhibitors from the HAART regimen. DTG is a new generation integrate single strand transfer inhibitor anti-retroviral medication. Currently, the ideal first-line HAART regimen for People living with human immune virus (PLHIV) is DTG coupled with two nucleoside/nucleotide reverse-transcriptase inhibitors.⁸ The regimen change to DTG-based HAART is being made for a number of reasons, including once-daily dosing (to increase adherence), acceptability, greater efficacy, fewer drug-drug interactions, and a better barrier to resistance than current non-nucleoside reverse transcriptase inhibitor (NNRTIs) based regimens.⁹ Integrate single strand transfer inhibitors have been recommended as the best regimen for HIV-infected children and adolescents. Interesting pharmacokinetic/pharmacodynamics characteristics of DTG includes a longer intracellular half-life and absence of unfavorable interactions with other anti-retroviral medications.¹⁰

It is commonly reported that children’s adherence to ART is sub-optimal.¹¹ Though evidence-based regimen changes are being applied incessantly for better ART therapeutics, adherence to those regimens should also be continuously monitored. A retrospective cohort study on non-adherence toward dolutegravir-based regimens found poor adherence which was predicted to be due to alcohol use, stigma, forgetting to take medication, transport problems, and irregular timing of swallowing.¹² In some cases the regimen changes or other determinants may enhance adherence toward ART. High adherence levels (71%) were observed from dolutegravir-based antiretroviral regimens among HIV infected children and adolescents in Tanzania.¹³ Even though a limited expanse of studies reported ART adherence levels toward dolutegravir-based regimens, especially in children, literatures are scarce in the context of Ethiopia. Hence, the main aim of this research was to assess the adherence to DTG-based antiretroviral therapy and its associated factors among children in public health institutions, Bahir Dar City Administration, North East Ethiopia.

Methods and Materials

Study Area and Setting

An institutional-based cross-sectional study was conducted among the ART clinics in Bahir Dar City Administration public health institutions from March 01 to April 31, 2023. Bahir Dar is the capital city of Amhara regional state located in Northwest Ethiopia located. The current projected population estimation is 389 177 of which, 147 983 are children under the age of 15 years.³ Around 691 children are on DTG based HAART. The city administration has 3 public hospitals and 10 health centers. Pediatrics ART services have been delivered in all public health facilities. Around 40 health workers have pediatric ART training who have been working on this important issue.

Source Population and Study Population

All children who have been taking HAART and on ART follow up at Bahir Dar City Administration public health institutions were considered as source population for this survey. From this, children’s care givers whose children are on DTG-based ART at the study area were considered as the study population.

Inclusion Criteria and Exclusion Criteria

Children aged up to 19 years old, and on first line DTG based HAART regimens and taking the drug at least 1 month was included as a study participant. However, children and adolescents with co-morbidity like DM, tuberculosis (TB), liver disease, and renal disease and those were not volunteer to participate in the study were excluded.

Sample Size Determinations

The sample size for this study was determined using the formula for a single population proportion, assuming a 95% confidence level and a 5% margin of error. Given the lack of prior data on the target population, a proportion of 50% was assumed, as this maximizes the sample size and ensures a conservative estimate. Using this assumption, the sample size was calculated to be approximately 384 participants.

n = \frac{{(Z_{a / 2})}^{2} P (1 - P)}{d^{2}}

Where,

n = sample size,

P = proportion rate,

Z α/2 = Z score at 95% CI

d = 5% (margin of error to be tolerated)

The minimum sample size calculated by using single population formula was 384.

After considering 10% non-response rate, the final sample size was 384 + 38.4 = 422.4 = 423.

Data Collection

Data was collected by using a pretested and structured questionnaire administered by face-to-face interviews with caregivers by three trained health care providers. The questionnaire, attached as a supplementary material to this article, was taken from pediatric AIDS clinical trial group (PACTG) adherence follow up questionnaire and different literatures.²¹ Adherence was measured using the caregivers’ monthly report of the treatment and the number of times they recalled missing doses. Patients/caregivers who reported an intake of more than 95% of the prescribed medications were considered to be good adherent. Medical charts were reviewed to determine clinical classification of the children.

Data Quality Control

Data were collected using a pretested questionnaire administered by trained health care providers. Prior to the actual data collection, a pretest was conducted with 34 (5%) clients at GAMBY General Hospital over 2 weeks to assess the clarity of the questions, the validity of the instrument, and participants’ reactions. Data collectors and supervisors received half-day training and clear orientation on the data collection process, including how to administer the structured questionnaire and approach participants. Continuous supervision was implemented throughout the data collection to ensure quality and consistency. Additionally, data from each ART site were reviewed for completeness, clarity, and consistency by the authors and supervisors on the day of the interview. Data were further checked for accuracy and consistency before entry and analysis.

Data Analysis

Data were coded and entered into EPI Info version 4.6, a software tool for data management and statistical analysis, before being exported to SPSS Windows version 26 for further analysis. Adherence to DTG based HAART was assessed by using caregiver self-reporting methods. Data presented as tables, charts, graph, and proportions (percentages) for descriptive analysis. Bi-variable logistic regression was used to check variables associated with the dependent variable. Those variables found to have P-values of ≤.25 were fit to multi-variable logistic regression to control the effects of confounders. Odds ratios with 95% CI were computed and variables having P-values <.05 in the multi-variable logistic regression models were considered significantly associated with the dependent variable. Model fitness was checked with the assumptions of Hosmer and Lemeshow goodness of a fit test (P > .05).

Results

Socio-demographic Characteristics

A total of 400 caregivers with the response rate of 94.6%, responded to the questionnaire. Of the respondents; 309 (77.3%) were females. 272 (68%) were orthodox in religion. Nearly two-third (63.5%) of the parents had college and above educational status. More than three-forth (77.8%) of the caregivers had a family size of ≤5. Most, 385 (96.3%) of the care givers interviewed were the biological parents of the children (Table 1).

Table 1.

Socio Demographic Characteristics of Children’s Caregiver in Assessing Adherence to DTG Based HAART (n = 400).

Variable	Frequency	Percent
Sex
Male	91	22.8
Female	309	77.3
Age
18-30	10	2.5
31-45	195	48.8
46-60	177	44.3
>60	18	4.5
Residency
Urban	358	89.5
Rural	42	10.5
Distance from health center (km)
<10 km	285	71.3
>10 km	115	28.7
Religion
Orthodox	272	68.0
Muslim	101	25.3
Protestant	27	6.8
Others	—	—
Marital status
Single	—	—
Married	264	66
Divorced	63	15.8
Widowed	73	18.3
Educational status
Unable to read and right	37	9.3
Read and right	38	9.5
Primary school (1-8)	43	10.8
Secondary school (9-12)	28	7.0
College and above	254	63.5
Occupation
Governmental employee	170	42.5
Merchant	162	40.5
Farmer	11	2.8
Daily laborer	8	2.0
House wife	49	12.3
Parent type
Biological	385	96.3
Non biologic	15	3.8
Family size
<5	311	77.8
>5	89	22.2

Of the total 400 children, half (50.3%) of the respondent were male and 361 (90.3%) were between the ages of 10 to 15 years. Nearly half, (48%) and 154 (48.5%) of the children were attending primary and secondary school respectively (Table 2).

Table 2.

Socio Demographic Characteristics of the Child Receiving DTG Based HAART (n = 400).

Variable	Category	Frequency	Percent
Sex of child	Male	201	50.3
Sex of child	Female	199	49.7
Age of child	0-4	18	4.5
	5-9	21	5.3
	10-15	361	90.3
Educational status of the child	Not going to school	14	3.5
	Primary school (Grade 1-8)	192	48
	Secondary school (9-12)	194	48.5

Clinical and Anthropometric Characteristics

The clinical characteristics of the children and their caregivers revealed that the majority of the children, 262 (65.5%), were classified as WHO stage I. Most of the children, 308 (77%), had CD4 counts greater than 500 cells/mm³, and a significant proportion, 283 (70.8%), had their HIV status disclosed. The largest proportion, 284 (71%) of the children were on TDF+3TC+DTG based regimen and 393 (98.3%) of them had a viral load between 0 and 50. About 83% of the children were on ART for more than 60 months. Most of the children, 360 (90.5%) had no any comorbidity illnesses. Most of the caregivers, 355 (88.8%) of them were sero-positive for HIV but all of them were on ART (Table 3).

Table 3.

Clinical Characteristics of the Child and Care Giver in Assessing Adherence to DTG Based HAART (n = 400).

Variable	Category	Frequency	Percent
Child HIV status disclosure	Yes	283	70.8
Child HIV status disclosure	No	117	29.2
Care givers HIV status	Positive	355	88.8
Care givers HIV status	Negative	45	11.2
Care giver on ART	Yes	355	100
Care giver on ART	No	—	—
CD4 category	<200	—	—
	200-500	82	23
	>500	308	77
Viral load	0-50	393	98.3
	51-1000	7	1.7
	>1000	0	0
WHO stage	Stage I	262	65.5
	Stage II	91	22.8
	Stage III	23	5.7
	Stage IV	24	6
Current regimen	AZT/3TC/DTG	2	0.5
	ABC/3TC/DTG	114	28.5
	TDF/3TC/DTG	284	71.0
Length of time on ART (month)	<36	24	4
	36-59	44	11
	>60	332	83
Comorbid illness	Yes	38	9.5
Comorbid illness	No	362	90.5

Most, 396 (99%) of the children had normal weight for height and 398 (97%) had normal weight for age. 372 (90%) had a normal body mass index for age. The general macro nutritional status of the children is good (Table 4).

Table 4.

Anthropometric Characteristics of the Child in Assessing Adherence to DTG Based HAART (n = 400).

Variable	Category	Frequency	Percent
WFH (weight-for-height)	Normal	396	99
WFH (weight-for-height)	Under weight	4	1
WFA (weight-for-age)	Normal	389	97
WFA (weight-for-age)	Under weight	11	23
BMI for age	Normal	372	90
	Under weight	23	5.75
	Obese	5	1.25

Abbreviations: WFH, weight-for-height = Z-score above −2 but below +2; WFA, weight-for-age = Z-score between −2 and +2; BMI-for-age Z-score between −2 and +1 was considered as normal.

Level of Adherence and Reasons of Poor Adherence

Of the total children taking ART, 40 (10%) of them had a history of missing at least one dose and 360 (90%) of them did not miss a single dose in the last month prior to the survey. So, the adherence level to HAART in HIV-positive children was 90% (Figure 1).

Figure 1.

Level of adherence toward DTG based HAART.

The commonly mentioned reasons for missing these medications were: forgetfulness 32 (47.8%), child’s refusal to take the drugs 21 (31.3%), and drug side effects 14 (20.9%) (Figure 2).

Figure 2.

Reasons for missing pill in children who are receiving DTG based HAART.

Factors Associated to DTG-based HAART Among Children

In the bi variate logistic regression analysis, factors significantly associated with adherence to dolutegravir-based HAART in children included family size, place of residence, distance from the health center (in kilometers), the child’s HIV disclosure status, CD4 count, and the presence of comorbidity illnesses. Variables that showed significance on bivariate analysis were introduced into multiple logistic regression (Table 5).

Table 5.

Bi-variate Analysis to Identify Factor Associated to Adherence to DTG Based HAART.

Variable	Category	Adherence level		P-value	COR 95% CI
Variable	Category	Good	Poor	P-value	COR 95% CI
Age of child	0-4	11	7		1
	5-9	14	7
	10-15	320	41	.002	4.967 (1.824, 13.56)
Family size	<5	298	13	.018	(1.210, 7.537)
Family size	>6	82	7		1
Place of residency	Urban	347	11	.000	(3.325, 22.258)
Place of residency	Rural	33	9		1
Distance from health center (km)	<10 km	280	5	.000	(2.974, 23.707)
Distance from health center (km)	>10 km	100	15		1
Disclosure status of the child	Yes	274	9		1
Disclosure status of the child	No	106	11	.013	(0.128, 0.786)
CD4 count of child	200-500	83	9		1
CD4 count of child	>500	291	11	.000	3.154 (1.739, 5.719)
Comorbid illness of the child	Yes	17	12		1
Comorbid illness of the child	No	363	8	.001	(1.610, 7.281)

During the bivariate analysis, variables with a P-value < .2 were entered into multivariable analysis. Multivariable analysis was performed with backward Wald Regression variable selection method and variables which had P-value < .05 were generally considered as statistically significant (Table 6).

Table 6.

Multivariant Analysis to Identify Factor Associated to Adherence to DTG Based HAART.

Variable	Category	Adherence level		P-value	AOR 95% CI
Variable	Category	Good	Poor	P-value	AOR 95% CI
Age of child	0-4	11	7		1
	5-9	14	7	.546
	10-15	320	41	.031*	3.875 (1.130, 13.291)
Disclosure status of the child	Yes	274	9	.008*	3.96 (1.43, 10.916)
Disclosure status of the child	No	106	11		1
CD4 count of child	200-500	83	9	.002*	3 (1.483, 6.069)
CD4 count of child	>500	291	11		1
Comorbid illness of the child	Yes	17	12	.006*	0.3 (0.132, 0.707)
Comorbid illness of the child	No	363	8		1

Significantly associated factor.

From the 6 included variables in multivariable analysis, 4 of the variables were found to be significantly associated with the outcome variable. Goodness of model fitness was tested and the result of Hosmer and Lemewhow test was 0.584. Children between 10 and 15 years of age were 3.8 times more likely to have good adherence to HAART than those between 5-9 and 0-4 of age (AOR = 3.877 [1.130, 13.291]). Children who were disclosed their HIV-serostatus were 3.96 times more likely to adhere to the medication as compared with those who were not disclosed (AOR = 3.96 [95% CI: 1.43, 10.916]). Children who had CD4 counts ≥500 were 3 times more likely to adhere to HAART as compared to CD4 counts between 200 and 500 (AOR = 3 [1.483, 6.069]). Children having comorbid illnesses were 70% less likely to adhere to the medication as compared to those who have not comorbid illnesses (AOR = 0.3 [0.132, 0.707]).

Discussion

In this study, the overall DTG-based HAART adherence among children who have follow up in Bahir Dar City Administration public health institutions were 90%. Our findings are almost consistent with a study conducted in New Delhi, in 2011 (91.4%),¹⁴ East Africa in 2018, 90%,¹⁵ and Southeastern Nigeria in 2017, 91%.¹⁶ Locally, Ethiopian national pooled prevalence in 2018 was 88.8%.¹⁷ Other local data on the level of adherence showed; Eastern Ethiopia, 90.7%,¹⁸ Mekelle hospital, 90.7%,¹⁹ and Gondar University Hospital and Gondar Poly Clinic, 90.4%.²⁰ The treatment adherence level found in this study was higher in comparison to studies conducted previously in Ethiopia (80.9%),²¹ Nigeria (80%),²² Togo (80%),²³ India (77%).²⁴ This finding was also higher as compared to studies conducted in China which was 77%,²⁵ 42% in West Africa,²⁵ and 76.1% in Nigeria.²⁶

In this study, treatment adherence to ART was significantly associated with the age of the children. As the age of the child increase, the level of adherence to treatment would also increase which is consistent with other studies conducted in Nigeria²² and Togo.²³ This increase could be because of the knowledge, level of understanding to the diseases, and there would be an increase responsibility for their own health. Disclosure is a critical step and has implications for adherence of medications. Starting disclosure as early as 10 years of age and combining it with specific support is important to increase children’s adherence as they get older.²⁷ In our study, the level of adherence was significantly higher in children who were aware of their serostatus than in those who are unaware of their status. This finding is consistent with studies from Uganda²⁷ and Democratic Republic of Congo.²⁸ These studies suggested that there were correlations with professional and ongoing counseling after disease disclosure to children.

The study demonstrated that children whose current CD4 count of 500 or greater have good adherence to the treatment. It could be surmised that long-term adherence leads to higher CD4 counts and CD4 increases as a result of optimal adherence to ART. On the other side, children having comorbid illness decrease the level of adherence which was in line with other studies.²⁹ This might be due to the summative effect of suffering from the chronic conditions. In addition to this, medication for coinfections, treatment, and ART together could contribute to increased pill burden, drug– drug interactions, and more adverse drug effects. These could be some of the reasons for the decrement in adherence to antiretroviral drugs.

Strengths and Limitations of the Study

Since there was no sufficient study conducted on this topic, it would be an input for further studies. This multicentric study was done at different set up which is high representative of those who lives with HIV in the population. This study had some limitations that needs consideration when interpreting the results. First, since the level of adherence was assessed using caregivers’ reports, this might be prone to recall bias. In addition, the data was gathered through interview which could increase the potential to social desirability bias. Furthermore, this study did not assess the awareness of HIV and HAART among the older children and the possible effect of this on the degree of adherence.

Conclusions

In this study, the level of adherence to dolutegravir-based antiretroviral therapy was found to be good in the vast majority of the study participants. Level of adherence could be affected by different factors but in this study; age of the child, disclosure status of the child, CD4 count of the child, and Comorbid illness of the child were factors that showed association with the adherence to DTG-based HAART.

Recommendation

For policy makers and health institutions; it is very crucial to evaluate and address any factor that is associated with poor adherence. The system should have a mechanism to monitor this and strategies should be compulsory to the professionals. And, this should bring significant attention for stakeholders at any level. For health professionals; Professionals should evaluate conditions associated with poor adherence and clinicians shall be meticulous in addressing such conditions as early as possible. It is very important to strongly advise and counsel the caregivers toward disclosing the HIV status to the child. A thorough assessment of comorbidity conditions is essential as it is one of the reasons and also the outcome of poor adherence. For caregiver’s; disclosure of HIV status to children has a paramount importance for good adherence, which affects their general health condition significantly.

Supplemental Material

sj-docx-1-gph-10.1177_30502225251314349 – Supplemental material for Adherence to Dolutegravir-Based Antiretroviral Therapy and Its Associated Factors Among Children Living With HIV in Bahir Dar City Administration Public Health Institutions, North West Ethiopia

Supplemental material, sj-docx-1-gph-10.1177_30502225251314349 for Adherence to Dolutegravir-Based Antiretroviral Therapy and Its Associated Factors Among Children Living With HIV in Bahir Dar City Administration Public Health Institutions, North West Ethiopia by Sefiw Abere Zeleke, Adugna Tasew Tebabal, Awoke Kebede, Ashagrachew Tewabe Yayehrad, Dagninet Derebe Abie, Ebrahim Abdela Siraj, Zekarias Tadele Alemneh and Sileshi Mulatu in Sage Open Pediatrics

Footnotes

Acknowledgements

The authors are grateful to Bahir Dar University for giving the ethical clearance. We are so grateful for department of Pediatrics and Child Health Nursing for the motivating us to do the research. We are grateful for all health centers and hospitals for allowing us to collect data and all respondents of the study for their willingness and genuine response.

Abbreviations and acronyms

AIDS - Acquired Immune Deficiency Syndrome, DTG - Dolutegravir, TDF - Tenofovir Disoproxil Fumerate, 3TC - Lamivudine, AZT - Zidovudine, HAART - Highly Active Anti-Retroviral Therapy, HIVDR - Human Immune Virus Drug Resistance, INSTIs - Integrase Strand Transfer Inhibitors, NNRTIs - Non-Nucleoside Reverse Transcriptase Inhibiters, PACTG - Pediatric AIDS Clinical Trial Group, PLHIV - patient live with HIV.

Authors’ Contributions

All authors made a significant contribution to the work reported; in the conception, study design, execution, acquisition of data, analysis and interpretation, drafting, revising or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article was submitted; and agree to be accountable for all aspects of the work.

Availability of Data and Materials

All data relevant to this study are available on the manuscript. The data used and/or analyzed during the current study are available from the corresponding author who could be forwarded upon request.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval and Consent to Participate

Ethical clearance was obtained from the Institutional Review Board (IRB) of College of Medicine and Health Sciences, Bahir Dar University with the following IRB decision information (the official letter is attached below).

• Meeting No: Expedite Review/2023

• Protocol No: 714/2023

• Date: March 06, 2023

Official letters was written to the study setting hospital. Participants were informed about the purpose and objective of the study. Respondents were also being told the right not to respond to the questions if they don’t want to respond or to terminate the interview at any time and verbal consent was obtained from each study participant. Confidentiality of the information was assured and privacy was also maintained.

Ethical Consideration

Ethical clearance was obtained from the ethics committee of College of Medicine and Health Sciences, Bahir Dar University (reference letter no. 01/28/10/2013). Officials letters was written to the study setting hospital. Participants were informed about the purpose and objective of the study. Respondents were also being told the right not to respond to the questions if they don’t want to respond or to terminate the interview at any time and verbal consent was obtained from each study participant. Confidentiality of the information was assured and privacy was also maintained.

Consent for Publications

All authors are willing for the publication of the research work.

ORCID iD

Ashagrachew Tewabe Yayehrad

Supplemental Material

Supplemental material for this article is available online.

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