Determinants of antiretroviral therapy adherence among people living with HIV in South Sulawesi, Indonesia: a cross-sectional study from SIHA 2.1

¹Faculty of Pharmacy, Hasanuddin University, Makassar, South Sulawesi, Indonesia, ²Department of Medicine, Faculty of Medicine, Hasanuddin University, Makassar , Indonesia, ³Institute for Research and Community Service, Hasanuddin University, Makassar, South Sulawesi, Indonesia, ⁴Department of Pharmacy, Sembilanbelas November University, Kolaka, Indonesia, ⁵Robotics and Artificial Intelligence Study Program, Faculty of Advanced Technology and Multidiscipline, Airlangga University, Surabaya, Indonesia, ⁶Robotics, Mechanics, and Intelligent System Research Group, Universitas Airlangga, Surabaya, Indonesia, ⁷Faculty of Public Health, Tompotika University, Luwuk, Central Sulawesi, Indonesia, ⁸Directorate for Measurement and Indicators of Research, Technology, and Innovation, National, Research and Innovation Agency Republic of Indonesia (BRIN), Jakarta, Indonesia, ⁹Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

^&Corresponding author
Bustanul Arifin, Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, South Sulawesi, Indonesia

Introduction    

Human immunodeficiency virus (HIV) remains a major public health challenge worldwide. As of the end of 2023, an estimated 39.9 million people live with HIV globally, according to the World Health Organization [1]. To address the challenge of HIV, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 95-95-95 targets in 2030, aiming for 95% of people living with HIV to know their status, 95% of those diagnosed with HIV to receive treatment, and 95% of those on treatment to achieve viral suppression [2]. Despite advances in antiretroviral therapy (ART), many countries have not achieved these targets yet. Achieving viral suppression strongly depends on optimal adherence to antiretroviral therapy (ART). Adherence is defined as the patient following the treatment plan by taking antiretroviral drugs at the appropriate time, in the appropriate dose, in the correct manner, and consistently [3,4]. While global progress has been uneven, country-level performance has varied widely, with some regions lagging significantly in terms of ART adherence and viral suppression. Indonesia is one such setting, where HIV remains a considerable burden. In Indonesia, the Ministry of Health reported 526.841 people were living with HIV (PLHIV) in 2022 and estimated 515,455 PLHIV in 2023, with a cumulative number of AIDS cases reaching 142,009 by September 2022 [5]. However, national progress toward UNAIDS targets remains suboptimal. As of December 2022, only 81% of PLHIV knew their status, 41% of those diagnosed with HIV were on antiretroviral therapy (ART), and only 19% of those treated achieved viral suppression [6]. These figures highlight substantial gaps in adherence and treatment outcomes, which remain key barriers to HIV control in this region. Antiretroviral therapy ( adherence is shaped by interacting sociodemographic and clinical factors that may influence patients’ capacity and motivation to maintain long-term treatment. Sociodemographic characteristics, including age, sex, marital status, education, employment or income, and place of residence, may affect adherence through differences in health literacy, economic resources, social support, access to health services, and the ability to maintain regular medication-refill routines [4,7-9]. Clinical characteristics may influence adherence through perceived disease severity, treatment burden, and patients’ experiences of illness and recovery. For example, individuals with more advanced clinical disease may perceive a greater need for consistent treatment, whereas those who are asymptomatic or in earlier clinical stages may perceive less immediate benefit from strict adherence [8,9].

Clinical indicators, such as cluster of differentiation 4 (CD4+) cell count and viral load, are therefore relevant not only as markers of treatment response but also as measures that may reflect patterns of sustained ART use. Together, these pathways provide a conceptual basis for examining the sociodemographic and clinical determinants of ART adherence in the present study. In Indonesia, the HIV/AIDS Information System (SIHA) is used to record and report HIV/AIDS services. Although SIHA has been implemented nationally as a routine HIV surveillance system, its use for epidemiological research has remained limited because earlier versions primarily supported program monitoring rather than research-oriented analyses, and access to individual-level programmatic data has been restricted. The implementation of SIHA 2.1, with improved individual-level recording and standardized clinical variables, provides an opportunity to evaluate ART adherence using routine, real-world program data. However, very few studies have utilized SIHA data, particularly in South Sulawesi, a region with a considerable HIV burden but limited evidence-based analyses of treatment adherence. Previous studies have primarily focused on Java-based populations based in Java, leaving significant knowledge gaps regarding adherence determinants in Eastern Indonesia, where cultural, geographic, and healthcare access factors differ substantially. Understanding adherence determinants in such settings is crucial for designing scalable interventions applicable to similar tropical, resource-limited regions in Southeast Asia and beyond. The implementation of the SIHA as an individual-level real-time recording and reporting system has created new opportunities to generate more accurate and locally relevant programmatic data [5]. South Sulawesi has one of the largest numbers of cases in Indonesia. South Sulawesi is a referral center in Eastern Indonesia. Few studies have used the SIHA 2.1 data source. It has been implemented and socialized since mid-2023. Unlike previous studies that relied on hospital-based samples or primary data collected from single facilities, the present study analyzed province-wide routine programmatic data using a census sampling approach, thereby providing findings that are more representative of routine HIV service delivery in Eastern Indonesia. The knowledge gap addressed by this study is due to the fact that previous studies on compliance based on determinant factors have not utilized the SIHA 2.1 as a data source. Therefore, this study analyzed ART adherence levels and identified sociodemographic and clinical factors associated with adherence among people living with HIV (PLHIV) in South Sulawesi using the SIHA 2.1 database. The findings are intended to inform targeted interventions and progress toward Indonesia’s and the global UNAIDS 95-95-95 targets.

Methods     

Study design and setting: this study employed an analytical observational cross-sectional design using retrospective routine data obtained from the HIV/AIDS Information System version 2.1 (SIHA 2.1). The study was conducted in South Sulawesi Province, Indonesia, and utilized programmatic data routinely collected from public HIV care facilities that reported to SIHA 2.1. The data covered the period from July 1, 2023, to April 30, 2025, reflecting standard antiretroviral therapy (ART) service delivery and monitoring within the provincial HIV program. All exposure variables and ART adherence outcomes were assessed using data available at the time of extraction, consistent with a cross-sectional analytical design

Participants: the study population included PLHIV registered in SIHA 2.1 in South Sulawesi Province during the study period who received ART and had complete records of ART adherence, sociodemographic characteristics, clinical conditions, CD4 cell counts, and viral loads. Individuals who initiated ART before the study period or had unverifiable or invalid records were excluded from the study. In total, 400 eligible participants were included using a census sampling approach with no matching procedure.

Data sources, variables, and measurement: data were obtained from the SIHA 2.1 system through the South Sulawesi Provincial Health Office, following formal authorization. SIHA 2.1 is a national, real-time HIV recording and reporting system used in public healthcare facilities in Indonesia. The primary outcome was ART adherence, assessed using pharmacy refill records and pill counts, and calculated as the percentage of days covered by medications during the observation period. Patients routinely received a 30-day ART supply per visit, with dispensing dates and quantities systematically recorded by pharmacy staff, and the measurement procedures were consistent across all reporting facilities. ART adherence was categorized as low (<80%), medium (80-95%), or high (95-100%) [10-12]. The independent variables included sociodemographic characteristics (age, sex, occupation, education level, marital status, residence, and population group) and clinical characteristics (WHO clinical stage, duration of therapy, functional status, opportunistic infections, CD4 cell count, viral load, and ART regimen), selected based on prior evidence of their association with adherence to ART. Continuous variables, including CD4 cell count, were summarized using means and standard deviations, and viral load was categorized using clinically relevant thresholds (<50, 50-1000, and >1000 copies/mL). The duration of therapy was dichotomized as ≤12 or >12 months, in accordance with programmatic reporting standards.

Bias: potential sources of bias included information bias arising from incomplete or inaccurately recorded routine program data and misclassification of ART adherence, as pharmacy refill records and pill counts may have overestimated the actual medication intake. Selection bias was minimized by applying a total population (census) sampling approach, in which all eligible records within the study period were included, thereby reducing the systematic exclusion of specific groups of participants.

Statistical analysis: the data were exported to the SPSS software for analysis. Descriptive statistics are presented as frequencies and percentages for categorical variables and means (standard deviation) or medians (interquartile range) for continuous variables, depending on their distribution. Associations between ART adherence and independent variables were assessed using the chi-square test or Fisher’s exact test for categorical data, and the independent t-test or Mann-Whitney U test for continuous data. Variables were selected a priori based on previous evidence and their theoretical and clinical relevance to ART adherence, rather than solely on statistical significance in the bivariate analysis. Accordingly, employment status, WHO clinical stage, and opportunistic infections were included in a multivariable logistic regression model. For the regression analysis, adherence was dichotomized into high adherence (≥95%) and non-high adherence (<95%), with high adherence defined as the reference outcome. This threshold was selected because it has traditionally been regarded as the benchmark for optimal ART adherence and virological suppression in previous adherence studies and international monitoring guidance [13]. The results are reported as odds ratios (ORs) with 95% confidence intervals. Missing data were analyzed as recorded, without imputation. Statistical significance was set at p <0.05.

Ethical considerations: the study protocol was reviewed and approved by the Pharmacy and Health Research Ethics Committee of the Faculty of Pharmacy, Hasanuddin University (approval no. 1375/UN4.17/KP.06.05/2025). As this study used de-identified secondary program data, the requirement for individual informed consent was waived in accordance with national regulations and institutional ethical guidelines.

Results     

Participants and descriptive data: the analysis included 400 eligible participants; all participants had complete data on antiretroviral therapy (ART) adherence and key sociodemographic and clinical variables. No eligible records were excluded after data verification. Most participants were aged 19-44 years (89.3%), with a predominance of male participants (85.0%). More than half of the participants were unemployed (52.8%), and 26.0% were engaged in business-related occupations. Regarding educational attainment, 31.8% of the participants had completed senior high school, and 16.8% had attained university-level education, although educational data were unavailable for 44.8% of participants. Most participants were unmarried (70.0%) and resided in rural areas (63.0%). In terms of population group, men who have sex with men (MSM) constituted the largest proportion (66.0%), followed by the general population (28.0%) and female sex workers (6.0%) (Table 1). Clinically, more than half of the participants were classified as having World Health Organization (WHO) clinical stage 1 disease (54.0%), while 31.0% were in advanced stages (stages 3 or 4). Opportunistic infections were absent in 68.5% of the participants; however, oral candidiasis (13.3%) and tuberculosis (10.0%) were the most common infections. Most participants had been on antiretroviral therapy for ≤12 months (64.5%). Most participants were functionally classified as working (87.3%). High medication adherence (>95%) was observed in 59.8% participants. The most commonly prescribed antiretroviral regimen was TDF/3TC/DTG, used by 84.5% of participants. The mean CD4+ cell count was 242.93 cells/mm³ (SD 130.48), with values ranging from 30 to 575 cells/mm³. Viral load suppression (<50 copies/mL) was achieved in 80.5% of the participants, while 3.5% had high viral loads exceeding 1000 copies/mL (Table 2).

Antiretroviral therapy adherence outcomes: high ART adherence (>95-100%) was observed in 239 participants (59.8%); 148 (37.0%) demonstrated medium adherence (80-95%); and 13 (3.3%) had low adherence (<80%) (Figure 1). For inferential analyses, the medium- and low-adherence categories were combined as non-high adherence (<95%), and binary logistic regression was performed using high adherence (≥95%) as the outcome.

Main results: Table 3 presents the results of the bivariate analysis of factors associated with ART adherence among PLHIV. No sociodemographic, clinical, or treatment-related variables were significantly associated with ART adherence, as all p-values exceeded the predefined threshold for statistical significance (p>0.05). Male participants showed slightly higher odds of adherence than female participants, although the association was not statistically significant (OR=1.26; 95% CI: 0.72-2.19; p=0.416). Employed individuals were more likely to be adherent than unemployed participants (OR=1.34; 95% CI: 0.88-2.02; p=0.171); however, this association was not statistically significant. Similarly, higher educational attainment, unmarried status, rural residence, absence of opportunistic infections, longer duration of therapy, and viral suppression (<50 copies/mL) were associated with increased odds of adherence; however, all confidence intervals crossed the unity line, indicating no significant associations. Overall, these findings indicate that ART adherence in this cohort was relatively uniform across demographic and clinical subgroups, with no single factor demonstrating a statistically significant association in the univariate analysis. Table 4 summarizes the results of the crude and multivariate logistic regression analyses examining the factors associated with ART adherence among people living with HIV. After adjustment, none of the examined variables were statistically significantly associated with ART adherence (all p >0.05). Unemployment was associated with higher odds of ART adherence than employment status in both crude (odds ratio [OR] =1.34; 95% confidence interval [CI] = 0.88-2.02; p=0.171) and adjusted analyses (AOR=1.37; 95% CI = 0.88-2.02; p=0.171); however, this association was not significant. Participants in WHO clinical stages 2-4 showed higher odds of adherence than those in stage 1, with a stronger association observed after adjustment (AOR=1.68; 95% CI = 0.94-3.01), although this trend did not reach statistical significance (p=0.082). The absence of opportunistic infections was also associated with increased odds of adherence; however, this relationship remained non-significant after adjustment (AOR=1.55; 95% CI = 0.83-2.87; p=0.167). Overall, no independent predictors of ART adherence were identified in the multivariable model, as all adjusted associations were statistically insignificant (p>0.05). However, the absence of statistically significant predictors in this study is an important finding, which is likely due to other factors that indicate differences in terms of the characteristics, sample size, and methods used.

Discussion     

This study provides programmatic evidence of antiretroviral therapy (ART) adherence among people living with HIV (PLHIV) in South Sulawesi, Indonesia, using routine data from the National HIV/AIDS Information System (SIHA 2.1) database. Of the 400 participants, 59.8% achieved high ART adherence (>95%), and none of the sociodemographic or clinical variables examined were significant predictors of adherence. These findings indicate that adherence remains substantially below the UNAIDS 95-95-95 target and that factors traditionally associated with adherence did not demonstrate predictive utility in this programmatic context. This pattern highlights the persistent challenges in sustaining optimal adherence despite expanded ART access under the test-and-treat strategy, particularly in routine care settings in low- and middle-income countries [14,15]. The observed adherence level of 59.8% aligns with previous studies from Indonesia, which reported suboptimal adherence across diverse populations and settings [16-18]. The absence of significant predictors further suggests that adherence gaps in this setting may not be attributable to any single measurable characteristic but instead reflect broader, systemic, and contextual challenges. Compared with settings that have achieved higher adherence and viral suppression rates, Indonesia continues to face socioeconomic, structural, and psychosocial barriers that undermine long-term treatment engagement [19,20]. Although no sociodemographic or clinical variables were significantly associated with ART adherence in the multivariable analysis, several variables showed non-significant patterns that were epidemiologically plausible. Employment status, WHO clinical stage, and history of opportunistic infections demonstrated differences in the adjusted odds of adherence; however, these estimates did not reach statistical significance and should not be interpreted as evidence of independent predictive or causal effects. These patterns warrant further investigation in larger longitudinal studies [7,21].

The lack of statistically significant associations may partly reflect limited statistical power, residual confounding from unmeasured factors, and the inherent constraints of cross-sectional analyses using routine program data. This may also be due to the fact that this study was not designed to detect smaller effect sizes. Therefore, the absence of statistically significant associations should not be interpreted as evidence of no effect/assosiation, as the available sample size may have been insufficient to detect modest associations, as the available sample size may have limited the ability to detect modest effect sizes, increasing the possibility of a type II error. Participants in more advanced WHO clinical stages tended to demonstrate higher adherence than those in stage 1, a pattern that has been reported in other resource-limited settings [8,9]. Individuals initiating ART in the early asymptomatic stages may perceive fewer immediate benefits from strict adherence, potentially reducing their motivation to maintain consistent medication use. Although this trend did not reach statistical significance, it is consistent with previous observations and may warrant further investigation with important implications for the test-and-treat policy, underscoring the need for enhanced adherence counselling and risk communication among asymptomatic patients to sustain long-term treatment engagement [15]. Although not statistically significant, the observed direction of the effect was consistent with that of the previous literature. Employment status also demonstrated a positive trend in adherence, consistent with evidence that economic stability facilitates clinic attendance, medication refills, and management of indirect treatment-related costs [21,22]. Although ART is provided free of charge in Indonesia, indirect financial and social barriers may continue to hinder adherence among unemployed or economically vulnerable PLHIV, highlighting the importance of integrating social support mechanisms into HIV-care services. Participants without a history of opportunistic infections tended to have higher adherence rates than those with prior infections; this non-significant trend is biologically plausible and has been previously reported as a complex and potentially bidirectional relationship between adherence and clinical outcomes. Sustained adherence reduces the risk of opportunistic infections, whereas prior severe illness may complicate treatment continuity through treatment fatigue, increased pill burden or recurrent healthcare utilization [23].

These findings support the need for differentiated adherence support for individuals with complex clinical histories. A notable finding was the discrepancy between high ART adherence and viral suppression, with more than 80% of the participants achieving viral suppression despite fewer than 60% meeting the ≥95% adherence threshold. However, this discrepancy should be interpreted cautiously. Pharmacy refill records and pill counts are indirect measures and may not fully reflect actual medication-taking behavior, whereas viral suppression represents the cumulative biological response to treatment and may not correspond precisely to adherence measured during the same observation period. Similar patterns have been reported in settings where DTG-based regimens predominate, reflecting the high genetic barrier to resistance and pharmacological robustness of contemporary antiretroviral therapy [24,25]. Although this may allow some tolerance for imperfect adherence, sustained adherence remains critical to prevent long-term resistance and preserve treatment options, particularly in programmatic settings with limited access to second-line therapies [15]. In treatment-naïve trial participants, DTG administered at 50 mg once daily without pharmacologic boosting combined with a standard nucleoside backbone was shown to be non-inferior or superior to first-line regimens containing efavirenz, darunavir/ritonavir, or raltegravir, regardless of pretreatment viral load. DTG has few drug interactions and can be taken without regard to meals. Overall, DTG-based regimens demonstrate favorable tolerability and pharmacological robustness [24]. Therefore, the observed discrepancy likely reflects a combination of measurement-related, temporal, and pharmacological factors, rather than regimen robustness alone. Nevertheless, sustained adherence remains essential for maintaining long-term viral suppression and minimizing the risk of treatment failure and resistance. The interpretation of these findings should consider the methodological limitations inherent in the study design and data sources. The cross-sectional nature of the analysis precludes causal inference, and reliance on pharmacy refill records and pill counts may not fully capture the actual medication intake. Incomplete data for certain sociodemographic variables and the absence of information on mental health, stigma, substance use, and social support may have limited the adjustment for confounding factors. Nevertheless, the use of a large provincial dataset derived from the national reporting system provides valuable real-world insights into ART adherence patterns in eastern Indonesia.

From a broader One Health and health systems perspective, ART adherence should be understood within the interconnected social, environmental, and healthcare contexts that shape access to and continuity of HIV care. Although this study focused on human health data and did not directly assess animal or environmental determinants, barriers related to socioeconomic vulnerability, geographic access, and healthcare delivery illustrate the broader system-level conditions influencing treatment continuity. Strengthening integrated, equitable, and context-sensitive HIV services may support sustained ART adherence and broader population health goals. This study had several strengths. This is the first study in South Sulawesi to utilize SIHA 2.1 retrospective routine data to assess ART adherence, providing programmatically relevant evidence from one of the largest provinces in Eastern Indonesia. The use of a total population sampling approach minimized selection bias and enhanced the representativeness of the findings of the provincial HIV programme. However, several limitations should be considered when interpreting the results. First, the cross-sectional design precluded the assessment of temporality and causal inferences between the identified factors and adherence to ART. Second, reliance on routine secondary data may introduce information bias due to incomplete or inaccurately recorded variables, as reflected by missing data for some sociodemographic characteristics of the participants. Third, adherence measurements based on pharmacy refill records and pill counts may over-or underestimate true medication intake. Additionally, important factors such as ART side effects, mental health status, social support, and tuberculosis preventive therapy were not available in the dataset, potentially resulting in residual confounding biases. The findings of this study are most applicable to PLHIV receiving ART within public healthcare facilities in South Sulawesi and similar settings in Eastern Indonesia, where healthcare access, sociocultural contexts, and HIV service delivery structures resemble those captured in the SIHA 2.1. Although caution is warranted in extrapolating results to other regions or private healthcare settings, the use of a national reporting system enhances the relevance of these findings for comparable low-resource programmatic HIV care environments in Southeast Asia. Although no independent predictors of adherence were identified, the observed trends suggest that unemployed PLHIV, those in the early clinical stages, or those with a history of opportunistic infections may benefit from targeted adherence support. Strengthening counseling for patients initiating ART at an early stage, integrating socioeconomic support, and leveraging community-based and peer support mechanisms, particularly within key populations, may help improve adherence to ART. Future studies employing longitudinal designs and enriched clinical and behavioral data are needed to better understand adherence dynamics and inform more effective interventions.

Conclusion     

This study demonstrates that antiretroviral therapy (ART) adherence among people living with HIV (PLHIV) in South Sulawesi remains suboptimal, despite broad treatment access. Suggesting that adherence may be influenced by structural and contextual factors, No sociodemographic or clinical factors were identified as dominant predictors, suggesting that adherence challenges are shaped by a combination of structural and contextual factors within routine-care settings. This highlights the need for integrated adherence support in routine HIV services. From a One Health perspective, strengthening ART adherence requires integrated, patient-centered strategies that go beyond medication provision, including enhanced adherence counselling, support for socioeconomically vulnerable populations, and differentiated care for patients with complex clinical histories. Strengthening adherence support within routine HIV services is essential for achieving national and global HIV control goals.

Competing interests     

The authors declare no conflict of interest.

Authors' contributions     

Ina Farlina: contributed to the conceptualization, data curation, writing of the original draft, funding acquisition, manuscript design and editing. Irda Handayani: contributed to supervision, methodology review, providing feedback and critical input on research design. Muhammad Nasrum Massi: contributed to supervision, methodology review, providing feedback and critical input on research design. Akhmad Ardiansyah: contributed to formal analysis, data integration, data interpretation, manuscript design and editing. Sylmina Dalily Alkaff: contributed to writing-original draft, manuscript design and editing. Muhammad Syahrir: contributed to validation, reviewing manuscript structure and compliance with the journal template. Sudikno: provided feedback and critical input on the study design. Bustanul Arifin: contributed to the conceptualization and main research design, as well as the overall supervision of the study’s direction and substance. All the authors have read and agreed to the final manuscript

Acknowledgments     

We express our deepest gratitude to the South Sulawesi Provincial Health Office, Marianti A. Manggau, Ian Forbes, as well as to the office of Research and Publication (ORP) at the Faculty of Medicine, Public Health, 13 and Nursing Gadjah Mada University, 2nd floor of the Administration Building, especially Eric Hokoom and all parties who contributed to this research for their willingness to help facilitate and coordinate the research.

Tables and figure     

Table 1: demographic characteristics of people Living with HIV (PLHIV) (n = 400)

Table 2: clinical and treatment characteristics of people living with HIV (PLHIV) (n = 400)

Table 3: factors associated with antiretroviral therapy adherence among people living with HIV (PLHIV)

Table 4: multivariable logistic regression analysis of factors associated with antiretroviral therapy adherence among people living with HIV (PLHIV)

Figure 1: distribution of antiretroviral therapy adherence among people living with HIV in South Sulawesi, Indonesia, 2023-2025

References