Factors Associated With Viral Load Suppression Among Adults on Dolutegravir and Efavirenz: A Cross-Sectional Study in Papua,Indonesia

Abstract

Purpose

This study aimed to investigate factors associated with viral load (VL) suppression among adults on Dolutegravir (DTG) and Efavirenz EFV)-based regimens antiretroviral therapy (ART) in Papua, Indonesia.

Methods

A cross-sectional study was conducted in a referral hospital, Papua Province.

Results

A total of 300 PLWH had either EFV-based regimens (50%) or DTG-based regimens (50%) equally. The majority PLWH had unsuppressed VL (70%). The multivariate analysis among PLWH with EFV-based regimens showed that having TB (AOR = 5.74; 95% CI = 2.30-14.31) was significantly associated with unsuppressed VL. Being better quality of mental health (MCS) (AOR=0.95; 95% CI =0.92-0.99) decreased the likelihood of unsuppressed VL. Moreover, those with DTG-based regimens TB (AOR = 2.60; 95% CI = 1.06-6.37) was significantly associated with unsuppressed VL. Being better quality of MCS (AOR=0.97; 95% CI =0.94-1.00), and those with high necessity of ART (AOR = 0.83; 95% CI = 0.72-0.95) decreased likelihood of unsuppressed VL.

Conclusions

There is a need to raise awareness about increasing the number of PLWH with VL suppression, particularly those with DTG-based regimens. This study suggests that during the launch of new ART, healthcare providers must be educated to increase their knowledge of the new therapy.

Plain Language Summary

Background

Dolutegravir (DTG) has been on the list of antiretroviral therapy (ART) in Indonesia, in addition to Efavirenz (EFV) as the existing first line of ART. Several studies have shown that ART has transformed HIV from a fatal disease into a manageable chronic condition. Therefore, this study aimed to investigate the effectiveness of DTG- and EFV-based regimens in VL suppression among people living with HIV (PLWH) on ART in Papua, Indonesia.

Methods

A cross-sectional study was conducted on 1036 PLWH, and data were collected from a referral hospital. The sample population comprised people who were aged above 18 years, had a VL test in the last 6 months, and provided informed consent. A logistic regression model was used to analyze factors associated with VL unsuppressed.

Results

A total of 300 PLWH (median age 34 years) met the inclusion criteria, and patients had either EFV-based regimens (50%) or DTG-based regimens (50%) equally. The majority of the patients had no TB coinfection (74.3), were Papuans (73.0), and had undetectable VL (70%). In multivariate analysis, PLWH with EFV-based regimens showed that having TB (AOR = 5.740; 95% CI = 2.302-14.314) and low quality of mental health (MCS) (AOR=0.955; 95% CI =0.921-0.990) were significantly associated with unsuppressed VL. In addition, DTG-based regimens, TB (AOR = 2.603; 95% CI = 1.062-6.379), low MCS (AOR=0.970; 95% CI =0.942-1.000), and lower necessity of ART (AOR = 0.830; 95% CI = 0.725-0.951) also had a significant association.

Conclusions

Based on the results, there is a need to raise awareness about increasing the number of PLWH with VL suppression, particularly those with DTG-based regimens. This study suggests that during the launch of new ART, healthcare providers must be educated to increase their knowledge of the new therapy. In addition, comprehensive counseling must be provided to improve the mental health and quality of life of PLWH.

Keywords

Dolutegravir Efavirenz belief in medication HIV viral load PLWH

Introduction

The introduction of antiretroviral (ART) has saved millions of lives worldwide, transforming HIV from a fatal disease to a manageable chronic condition.¹ In addition to its ability to inhibit viral replication, ART can also increase the life expectancy of PLWH by improving the quality of life (QoL) and happiness to achieve health restoration.² Achieving one of the 95-95-95 global HIV targets, namely 95% of people living with HIV (PLWH) on ART must attain viral load (VL) suppression, may remain challenging due to certain barriers.

According to previous studies, more than half a million Indonesians are living with HIV, and the government has taken the initiative to provide free ART. With infection and mortality rates still higher in Indonesia than in other countries within the Asia-Pacific region, achieving the target has been reported to be a challenge. Multiple interventions have been targeted to reduce disparities in health among more than 17,000 islands in Indonesia.³ For example, Dolutegravir (DTG) was added to the national formulary in 2021. The drug was introduced to simplify medication regimens, provide ART with fewer adverse effects,⁴ and serve as a first-line therapy for people diagnosed with HIV.⁵

DTG has proven to be highly tolerated and effective in increasing health outcomes.⁶ In addition to Efavirenz (EFV), DTG-based regimens can also be used once a day due to their long plasma half-life⁷ and have been effective among PLWH with Tuberculosis (TB) comorbidity.⁸ A recent study showed that the number of PLWH with DTG-based regimens who achieved VL suppression was higher compared to those with EFV-based regimens.⁹ Several studies have also shown that DTG-based regimens have fewer problems of neuropsychiatric adverse effects, and easy to discontinue.¹⁰

Discontinuation of ART and low number of VL suppression among PLWH within Indonesia remains a significant problem. Lifetime ART not only undermines long-term health outcomes and VL suppression but also exacerbates issues, such as harm and overuse due to drug resistance and treatment failure.¹¹ It can also lead to worse symptoms, particularly among PLWH with low health literacy.¹² Updating and continuous training for healthcare providers, particularly DTG-based regimens as a new drug on the formulary list, is essential to belief in medication.

Papua is one of the underserved areas in Indonesia, with an HIV prevalence 24 times higher than the national prevalence and relatively low health literacy among PLWH.¹² The commitment of the regional and central government is shown by providing free ART and free VL testing for those who were on ART.¹³ However, DTG has been available in this area since 2024, which is later than in other areas. Therefore, this study aimed to investigate factors associated with VL suppression between PLWH with EFV- and DTG-based regimens in the Papua area of Indonesia.

Methods

Study Design and Setting

This cross-sectional study used questionnaires to assess beliefs about medicines between those with EFV-based regimens and DTG-based regimens. The participants comprised outpatients of a referral hospital in Jayapura, Papua Province, Indonesia, who provided written informed consent. After obtaining informed consent, an appointment for questionnaire completion was scheduled to be conducted during a visit to the hospital in the subsequent month.

Study Population and Eligibility Criteria

The participants were recruited using convenience sampling. Patients who had been on medication for more than six months, had a VL result from the previous six months, and had provided written informed consent were included in the selection criteria. Patients were excluded when more than 50% of the data were missing. Participants were recruited by a pharmacist student and 3 nurses working at the Voluntary, Counseling, and Treatment (VCT) Clinic at the hospital. Patients were informed about the study while obtaining their prescribed medicine in the waiting room. The healthcare professionals promised to store all information confidentially and clarified that participation decisions did not impact the treatment process in any way. During the appointment, participants were given 3 paper-based questionnaires along with an extra one to collect sociodemographic information, including age, gender, income, type of comorbidity, type of ART, marital status, ethnicity, and body composition BMI.¹⁴ These questionnaires were completed in the waiting area of the hospital and recruiters collected the data from February to June 2024.

Sample Size and Sampling Procedure

From 1036 PLWH who had commenced ART since 2006, but only 565 were eligible to be participants. The sample size was calculated based on the use of a 2-tailed test with a level of significance of 0.05. Approximately 77 % of total PLWH were registered and taking ART regularly in that hospital.¹⁵ Consequently, at least 288 participants were required to conduct the study. This were consequences of the regulation of patients taking medication was changed from monthly to every three months. Furthermore, Dolutegravir is recently on the list of ART in Indonesia and less than 8 months before the study conducted this drug has been administered to PLHIV and lack of reagent of VL often occurred in this area. Finally, a total of 300 PLWH met the inclusion participated in this study period.

Data Collection and Measurements

Beliefs About Medicines Questionnaire (BMQ)

The questionnaire was assessed through widely used instruments.^16,17 BMQ assessed the general concepts and beliefs of patients about the type of medication administered.¹⁶ The general part of this questionnaire consisted of 2 scales with 4 questions each, addressing views on overuse and harm related to medication. An example of a statement on overuse was, “Doctors used too many medicines”, and that of harm was: “Most medicines were addictive.” In addition, the specific part comprised 2 scales with 5 questions each addressing the necessity and concerns of patients regarding the medicine used. For instance, “My medication protects me from becoming worse” was a statement of necessity, and “I am sometimes worried about becoming too dependent on antiretroviral medication” was related to concern. All 18 statements were evaluated on a 5-point Likert scale of 1, 2, 3, 4, and 5, showing responses of “strongly disagree”, “disagree”, “uncertain”, “agree”, and “strongly agree”, respectively. The total score for every BMQ scale was calculated. Higher total scores on the necessity scale showed that the patients had a positive attitude towards and benefited from taking their prescribed medication. Moreover, higher total scores for the concern, overuse, and harm scales were associated with anxiety about the medication. The questionnaire was translated into Bahasa Indonesia.¹⁷

The Mental Component Summary (MCS) of the QoL SF-36

SF 36 questionnaire for investigating QoL worldwide consisted of 36 items across 6 domains, including physical functioning, physical role limitation, emotional role limitation, energy fatigue, emotional well-being, social functioning, pain, and general health. In addition, the version used in this study was translated and validated into the target language, Bahasa Indonesia.¹⁸ The 36-item questions were multiple choice with scores, which ranged from 0 to 100, where greater total scores correlated with higher levels of QoL domains. In this study, the subscales were also summarized into 2 summary components, namely the physical component summary (PCS) and the MCS. Higher SF-36 MCS scores showed better mental health-related QoL.

Data Management and Analysis

The analyzed independent variables included age, gender, marital status, number of children, education, employment, religion, and ethnicity, and responses to the BMQ questionnaire regarding necessity, concern, overuse, and harm. In addition, the dependent variable was the condition of VL, and the results were binary-coded as suppressed VL and unsuppressed VL. The threshold of VL is 200 copies/ml.¹⁹ Sociodemographic variables were analyzed via descriptive statistics. The categorical variables were presented as frequencies and percentages. Meanwhile, continuous variables were summarized in the form of mean or standard deviation. The association was analyzed using the Chi-square test for categorical variables and either the independent sample t-test or Mann-Whitney U test for continuous variables. The compiled questionnaire can be found in the supplemental material.

Statistical Modeling

In the descriptive analysis, univariate logistic regression was used to explore the impact of independent variables on suppressed VL. This was followed by multivariate logistic regression, where a backward elimination procedure was performed to identify the final model containing all significant variables with a p-value of ≤0.05. Subsequently, the odds ratio (OR) and 95% confidence interval (CI) were calculated. The entire analysis was carried out through 2-tailed tests at a significance level of 0.05 using the Windows Statistical Program for Social Sciences (SPSS) version 22.0.

Ethics Considerations

The study protocol was approved by the Committee on Ethics Universitas Muhammadiyah Banjarmasin Indonesia (No. KEPK: 0128226371). All study participants gave written informed consent.

Results

More than 1000 PLWH were eligible to participate in this study, but 300 PLWH were selected since the VL results in the past 6 months were presented. The median age was 34 years, and patients had either EFV-based regimens (50%) or DTG-based regimens (50%) equally often. The majority of participants had no TB coinfection (74.3), Papuans (73.0), and had VL suppression (70%). Almost an equal number were female (57.6%) and both EFV-based regimens (50%) and DTG-based regimens (50%). A slightly higher percentage of those with EFV-based regimens (51.4%) exhibited VL suppression status compared to those with EFV-based regimens (48.6%). A total of 150 PLWH with EFV-based regimens completed this survey, with a median score of MCS of 74.4 (interquartile ranges, IQR 62.1-83.3). Of which 150 PLWH with EFV-based regimens had a median score of MCS of 73.6 (interquartile ranges, IQR 58.6-82.1).

The median score of necessity were 20.0 (IQR) 17.0-22.0) in EFV-based regimens and 19.0 (IQR 17.0-22.0) in DTG-based regimens (Table 2). Domain of concern, overuse, and harm among PLWH with EFV-based regimens Of which 150 PLWH with EFV-based regimens had a median score of MCS of 73.6 (IQR 58.6-82.1). The concern scales were 14.0[11.75-17.0], 10.5[9.0-12.0], and 9.0[8.0-11.0], respectively. Among those with DTG-based regimens, concern, overuse, and harm scales were 14.0[11.0-17.0], 10.0[8.0-12.0], and 10.0[8.0-12.0], respectively. Those with MCS scores were performed, with a median number per participant of 74.4 (interquartile range (IQR) 62.1-83.3) in EFV-based regimens and 73.6 (58.6-82.1) in DTG-based regimens (Table 1).

Table 1.

Sociodemographic Characteristics of Participants for Having EFV and DTG Among PLWH

Characteristics		Number (n=300,100 %)	Antiretroviral
Characteristics		Number (n=300,100 %)	EFV based regimens (N=150)	DTG based regimens (N=150)
Age (years), median (IQR)		34 [28.0-41.0]	35.0[29.0-43.2]	32.0[27.0-39.2]
Gender	Female	172 (57.3)	92 (53.5)	80 (46.5)
Gender	Male	128 (42.7)	58 (45.3)	70 (54.7)
Disease	No TB	223 (74.3)	110 (49.3)	113 (50.7)
Disease	With TB	77(25.7)	40 (51.9)	37 (48.1)
Ethnicity	Papuan	219 (73.0)	109 (49.8)	110 (50.2)
Ethnicity	Non-Papuan	81 (27.3)	41 (50.6)	40 (49.4)
BMI	Normal	189 (63.0)	86 (45.5)	103 (54.5)
	Overweight	64 (21.3)	41 (64.1)	23 (35.9)
	Underweight	47 (15.7)	23 (48.9)	24 (51.1)
Viral Load	VL Suppression	210 (70.0)	108 (51.4)	102 (48.6)
Viral Load	Unsuppressed VL	90 (30.0)	42 (46.7)	48 (53.3)
MCS, median (IQR)		74.1[60.3-82.4]	74.4[62.1-83.3]	73.6[58.6-82.1]

*significant p-value ≤ 0.05; BMI, body mass index; MCS, Mental component summary.

Domain of necessity were 20.0(IQR) 17.0-22.0) in EFV-based regimens and 19.0 (IQR 17.0-22.0) in DTG-based regimens (Table 2). Domain of concern, overuse, and harm among PLWH with EFV-based regimens were 14.0[11.75-17.0], 10.5[9.0-12.0], and 9.0[8.0-11.0], respectively. Among those with DTG-based regimens, concern, overuse, and harm scales were 14.0[11.0-17.0], 10.0[8.0-12.0], and 10.0[8.0-12.0], respectively. Those with MCS scores were performed, with a median number per participant of 74.4 (interquartile range (IQR) 62.1-83.3) in EFV-based regimens and 73.6 (58.6-82.1) in DTG-based regimens (Table 2).

Table 2.

Descriptive Statistics of the BMQ Subscales and the MCS Scale Comparing Those With EFV and DTG

Characteristics			Antiretroviral
Characteristics			EFV based regimens (median, IQR)	DTG based regimens (median, IQR)
BMQ	Necessity	20.0[17.0-22.0]	20.0[17.0-22.0]	19.0[17.0-22.0]
	Concern	14.0[11.0-17.0]	14.0[11.75-17.0]	14.0[11.0-17.0]
	Overuse	11.0[9.0-11.0]	10.5[9.0-12.0]	11.0[9.0-14.0]
	Harm	9.0[8.0-11.0]	9.0[8.0-11.0]	10.0[8.0-12.0]
MCS		74.1[60.3-82.4]	74.4[62.1-83.3]	73.6[58.6-82.1]

IQR, interquartile range; MCS, Mental component summary.

The multivariate analysis among PLWH with EFV-based regimens showed that having TB (AOR = 5.74; 95% CI = 2.30-14.31) was significantly associated with unsuppressed VL, as presented in Table 3. Being better quality of mental health (MCS) (AOR=0.95; 95% CI =0.92-0.99) decreased the likelihood of unsuppressed VL. Moreover, those with DTG-based regimens TB (AOR = 2.60; 95% CI = 1.06-6.37) was significantly associated with unsuppressed VL. Being better quality of MCS (AOR=0.97; 95% CI =0.94-1.00), and those with high necessity of ART (AOR = 0.83; 95% CI = 0.72-0.95) decreased likelihood of unsuppressed VL.

Table 3.

Adjusted Logistic Regression of Sociodemographic Characteristics, BMQ, MCS and Unsuppressed VL Among PLWH (N = 300)

Characteristics		EFV based regimens		DTG based regimens
Characteristics		Univariate OR (95% CI)	Multivariate* aOR (95% CI)	Univariate OR (95% CI)	Multivariate* aOR (95% CI)
Gender	Female	REFF.	REFF	REFF	REFF
Gender	Male	0.96[0.46-2.01]	1.33[0.55-3.23]	1.21[0.61-2.42]	1.10 [0.47-2.56]
Disease	No TB	REFF	REFF	REFF	REFF
Disease	With TB	6.48[2.91-14.39]	5.74[2.30-14.31]	3.57[1.64-7.75]	2.60 [1.06-6.37]
BMI	Normal	REFF	REFF	REFF	REFF
	Overweight	0.50[0.19-1.28]	0.38[0.12-1.16]	0.46[0.14-1.48]	0.64[0.18-2.28]
	Underweight	1.87[0.72-4.83]	0.89[0.26-3.03 ]	2.21[0.90-5.47]	2.18[0.77-6.20]
Ethnicity	Papuan	REFF	REFF	REFF	REFF
Ethnicity	Non-Papuan	0.64[0.27-1.50]	0.95 [0.83-1.09]	0.52[0.22-1.22]	0.75[0.28-1.99]
BMQ	Necessity	0.99[0.88-1.10]	1.08[0.94-1.23]	0.86[0.77-0.97]	0.83[0.72-0.95]
	Concern	1.09[1.00-1.20]	1.05[0.90-1.23]	1.04[0.95-1.12]	1.04[0.92-1.17]
	Overuse	1.02[0.90-1.15]	0.99[0.83-1.19]	1.03[0.93-1.15]	1.06[0.90-1.24]
	Harm	1.10[0.90-1.14]	0.86 [0.71-1.05]	0.90[0.79-1.03]	0.31[0.68-1.00]
Age		0.98[0.95-1.02]	1.00[0.96-1.05]	0.99[0.95-1.03]	0.99[0.95-1.04]
Level of MCS		0.95[0.92-0.97]	0.95 [0.92-0.99]	0.97[0.95-0.99]	0.97[0.94-1.00]

BMI, body mass index; MCS, Mental component score.

Discussion

This study investigated factors associated with VL suppression among PLWH on EFV-based and DTG-based regimens in rural Indonesia. For those on EFV-based regimens, virological non-suppression was significantly associated with TB comorbidities and lower mental Quality of Life (QoL) scores. Similarly, while TB and low mental health scores affected the DTG group, these patients also faced an additional barrier: a lack of belief in the necessity of their medication, which further decreased the likelihood of achieving VL suppression. The results showed that only two-thirds of participants had VL suppression, a figure that was below the UNAIDS target of 95% for those on antiretroviral therapy.

To achieve VL suppression, PLWH must adhere strictly to their ART regimen, whether it is EFV-based or DTG-based. Beyond its better tolerability, higher genetic barrier to resistance, fewer adverse events, and lower cost, DTG-based regimens achieve VL suppression more rapidly than EFV-based regimens.²⁰ These advantages serve as the primary rationale for recommending DTG as the first-line ART in Indonesia, particularly as it has proven more effective at reducing treatment discontinuation compared to EFV.²¹ However, the results of this study present a notable contrast to these established findings.

This study found a similar proportion of VL suppression among patients on EFV-based regimens and those on DTG-based regimens. Although EFV-based regimens have been reported to cause neuropsychiatric adverse effects, sometimes of severe grade, patients receiving EFV were able to tolerate these effects and still achieve VL suppression. This suggests that individuals on EFV-based regimens may have developed a better understanding of the adverse effects and recognized the importance of continued ART for maintaining their health. Meanwhile, challenges observed among patients on DTG-based regimens may be attributed to insufficient information or counseling received from healthcare providers regarding the regimen and its potential effects.

DTG–based regimens are relatively recent antiretroviral therapies, and information about DTG has not been as well established as that for EFV–based regimens. Healthcare providers have longer prescribing experience with EFV and are more familiar with its adverse effect profile, which has been more commonly observed and documented than that of DTG-based regimens. Consequently, providers tend to be more confident in delivering counseling and guidance regarding EFV-based regimens, drawing on both established information and clinical experience with PLWH. Dissemination of information on newer antiretroviral drugs to healthcare workers in this setting appears to lag behind policy recommendations for their adoption. Comprehensive profiles of EFV, including indications, contraindications, dosage, and potential side effects, have been widely provided to healthcare providers to support safe and rational use. Consequently, patients receiving EFV-based regimens demonstrated stronger confidence in the necessity of continuing ART, while those on DTG-based regimens experienced more uncertainty.

Irrespective of the ART regimen, TB comorbidity was identified as a predictor of difficulties in achieving VL suppression among PLWH,²² particularly in Indonesia, which carries a high TB burden. The risk of TB infection among Indonesians is comparable to that in India.²³ HIV-induced immune system compromise increases susceptibility to opportunistic infections and comorbidities such as TB, which can further complicate VL suppression efforts.

Another predictor, regardless of ART regimen, was the mental aspect of quality of life (QoL), which significantly influenced PLWH’s adherence to medication and their ability to achieve VL suppression. Challenges related to mental health were present from diagnosis through chronic illness management and treatment. Prolonged stress not only damages the body ²⁴ but also suppresses the immune system, increasing vulnerability to other illnesses. Without addressing mental health and QoL issues, PLWH face greater difficulty achieving sustained VL suppression, regardless of the ART regimen. Maintaining lifelong, continuous VL suppression requires interventions that address both clinical and social factors to improve QoL. Long-term stress often stems from fear of stigma, related not only to HIV transmission but also to societal perceptions of sexual behavior, including homosexuality or multiple sexual partners. Counseling that emphasizes the benefits of ART and supports mental well-being should be an integral part of treatment from the start, helping PLWH navigate these challenges while promoting adherence and positive health outcomes.

There is a need to provide comprehensive, continuous counseling to strengthen PLWH’s belief in their ability to adhere to treatment,²⁵ as well as access to psychological services.²⁶ Additionally, educational programs tailored for healthcare providers should be prioritized in Papua, where there is a critical shortage of trained professionals. Such programs could enable providers to disseminate information about new treatments and medications more efficiently and accurately. The results suggest that achieving the 95-95-95 targets by 2030 may be challenging, as nearly one-third of PLWH failed to achieve VL suppression after more than six months on ART. Although the government has made efforts to ensure free ART for all PLWH, it is essential to initiate treatment immediately for all individuals, regardless of CD4 count or viral load. Early initiation of ART not only limits the spread of HIV and associated comorbidities but also slows disease progression, improving long-term health outcomes.

Limitation

Based on the results, the current study had some limitations. First, this study was carried out in a referral hospital for HIV/AIDS in Papua. The number of PLWH participants was low, and the results were not generalizable to other areas. Second, the SF-36 was validated among middle-aged and older people but not among people living with HIV. Third, this was a cross-sectional study, and it was difficult to draw causal inferences between HIV infection and chronic comorbidities or co-medications. The quality of data to predict VL in this study could not be prevented since the documentation of patients used paper-based and missing data could not be avoided.²⁷

Conclusions

In conclusion, this study suggests that the process of launching new ART must be consistent with the dissemination of information to healthcare providers to increase their knowledge of the new therapy. Comprehensive counseling must be provided to improve the mental health and QoL of PLWH.

Supplemental Material

Supplemental Material - Factors Associated With Viral Load Suppression Among Adults on Dolutegravir and Efavirenz: A Cross-Sectional Study in Papua, Indonesia

Supplemental Material for Factors Associated With Viral Load Suppression Among Adults on Dolutegravir and Efavirenz: A Cross-Sectional Study in Papua, Indonesia by Elfride Irawati Sianturi, Meidianti Modokh, Sitti N Soltief, Elmiawati Latifah, and Andre Anusta Barus in Journal of the International Association of Providers of AIDS Care (JIAPAC).

Footnotes

Acknowledgments

The authors are grateful to PLWH who participated in this study.

ORCID iD

Elfride Irawati Sianturi

Ethical Considerations

The study protocol was approved by the Committee on Ethics Universitas Muhammadiyah Banjarmasin Indonesia (No. KEPK: 0128226371).

Consent to Participate

All study participants, men and women, gave written informed consent.

Author Contributions

Conceived and designed the study: EIS, MM, EL, SNS. Analyzed the data: EIS, AA, MEP Wrote the paper: EIS, MM, SNS, EL, AA. All authors read and approved of the final manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the Faculty of Mathematics and Natural Sciences, Cenderawasih University, Papua, Indonesia, and provided to EIS. The funding sponsor had no role in the design of the study; in the collection, analysis, or interpretation of the results; in the writing section, and the decision to publish these results.

Declaration of Conflicting Interests

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

Data Availability Statement

The data would not be shared outside of the participating institutions, and any queries on how to access the data should be forwarded to the corresponding author.*

Author Disclosure Statement

No competing financial interests exist.

Supplemental Material

Supplemental material for this article is available online.

Appendix

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