Stigma Determines Antiretroviral Adherence in Adults with HIV in Myanmar

Abstract

Introduction:

Understanding social and structural barriers that determine antiretroviral therapy (ART) adherence can improve care. Assessment of such factors is limited in Myanmar, a country with high HIV prevalence and increasing number of people living with HIV (PLWH) initiating ART.

Methods:

Questionnaires were administered to adults with HIV across four Myanmar cities to estimate adherence and its potential determinants, including HIV knowledge, social support, barriers to care (BTC), enacted and internalized stigma, and engagement in peer-to-peer HIV counseling (PC). Associations were determined using logistic mixed-effects modeling.

Results:

Among 956 participants, mean age was 39 years, 52% were female, 36% had CD4 <350 cells/mm³ and 50% received pre-ART PC. Good adherence was reported by 74% of participants who had better HIV-knowledge than those reporting non-adherence. Among non-adherent, 44% were forgetful and 81% were careless about taking ART. Among all participants, most (53%) were very satisfied with their social support and 79% reported lack of financial resources as a BTC. Participants most frequently reported being viewed differently by others (30%) and feeling as if they were paying for past karma or sins due to their HIV diagnosis (66%). Enacted stigma (odds ratio (OR) 0.86; 95% confidence interval (CI) 0.79–0.92, p<0.01) and internalized stigma (OR 0.73; 95% CI 0.56–0.95, p=0.023) were associated with worse adherence.

Conclusions:

Increased self-reported ART adherence in Myanmar is associated with less enacted and internalized stigma. These findings suggest the benefit of developing and promoting adherence interventions, that are focused on mitigating HIV-related stigma in the county.

Introduction

Myanmar has the third highest prevalence of HIV in the Asia Pacific Region at 0.8%¹ and ranks as one of 35 countries which account for 90% of new infections globally ². Nearly 90% of the population in Myanmar identify as Buddhists, and amidst religious and societal conservatism, Myanmar was subject to decades of military rule. While ART became available in the country in 2005, surveillance efforts and widespread provision of treatment were challenged by low resources and outreach. In 2015, after a change in government, the country has ramped up its efforts to improve HIV care. In accordance, ART dispensing efforts began shifting from the private sector, managed by local and international non-governmental organizations, to the public sector, managed by the central government ³, and 70% of people living with HIV (PLWH) are currently on antiretroviral therapy (ART) ¹.

HIV treatment failure may result in drug resistance, morbidity and mortality ⁴. Measurement of ART adherence, the lack of which leads to treatment failure, was not standardized in Myanmar across ART dispensing sites due to scarce resources until 2018, when HIV viral load testing became more widely available in the country. However, treatment monitoring remains a challenge due to loss to follow-up and perhaps other unevaluated issues, such as routine challenges in incorporation of viral load testing into clinical care ⁵, limited switch to 2^nd line ART and lack of drug resistance testing ⁶.

Identifying and overcoming factors that reduce adherence are essential to sustain viral load suppression; however, their objective measurement can be difficult, particularly in resource-limited settings. Determinants of adherence include patient characteristics such as socioeconomic status, race, psychological stress, attitudes, beliefs, social relationships and extrinsic barriers to treatment ⁷. HIV knowledge among PLWH ^{8, 9}; structural barriers to care (BTC; e.g., financial resources, transportation, schedule conflicts) ⁷; and social peer support ^{10, 11}, have all been associated with ART adherence in diverse settings. Among predictors of ART adherence, HIV-related stigma has emerged as a negative correlate of engagement in HIV care ^{12, 13} in both developed and developing regions. Aye et al. examined correlations between markers of health including CD4 count, comorbidities and behavioral factors, with ART adherence in Myanmar and found that tobacco use and disclosing status to others were associated with non-adherence, while higher adherence was found among individuals with partners also on ART ¹⁴. Importantly, structural barriers and social factors that may determine ART adherence and can be modifiable, were not included and have not been examined in Myanmar. Examining ART adherence predictors, specifically within the Myanmar culture and infrastructure, is therefore imperative to best optimize allocation of limited resources toward targeted interventions to improve ART adherence.

To address this research gap, the aim of this study was to explore social determinants associated with ART adherence in Myanmar, to guide beneficial interventions and improve HIV care. Specifically, we hypothesized that increased HIV knowledge, fewer BTC, reduced stigma, higher satisfaction with social support, and engagement in PC are associated with improved ART adherence, and examine which of and the extent to which these parameters determine adherence in this unique population. Specifically addressing these hypotheses in Myanmar is essential, due to this country’s uniqueness with regards to conservative religious and social practices within a challenging political climate and resource limitations.

Methods

Study Setting

Participants were recruited from three organizations: National AIDS Programme (NAP), Pyi Gyi Khin (PGK), and Myanmar Positive Group (MPG). NAP is a governmental agency while PGK and MGP are non-governmental organizations (NGO). At the time of this study, these agencies provided HIV services including counseling and ART in distribution sites across four cities (Yangon, Pyay, Pathein, and Myingyan), based on national and World Health Organization guidelines. Adult first-line ART included efavirenz, tenofovir and lamivudine ¹⁵ and HIV viral load testing had not yet been widely implemented.

Study Design

We conducted a cross-sectional survey from May to October of 2016, using a convenience sample of PLWH aged 18 or older who attended their scheduled ART retrieval visits (every 1–3 months), completed all required pre-ART counseling (1–3 sessions), and initiated ART at one of the three participating agencies. Individuals below the age of 18, with incomplete pre-ART counseling, and those not taking ART were excluded. Trained local research staff, who were neither counselors nor healthcare professionals directly involved in the care of the participants, obtained written consent and distributed questionnaires in Burmese to eligible and consenting individuals. The study was approved by both the Institutional Review Board in Providence, RI (USA) as well as the Ethical Review Committee in Myanmar.

Questionnaires derived information about socio-demographic and clinical characteristics including age, gender, education level, duration of HIV, CD4 count, and mode of transmission. The primary outcome, ART adherence, was measured as a binomial variable of “non-adherent” (score ≥1) or “adherent” (score of 0), by a validated six-question simplified medication questionnaire ¹⁶ asking whether participants ever forgot, were at times careless about, or admitted to not taking their ART when feeling unwell; missed one or more doses of medications within the past week; skipped medications over the past weekend; or missed more than two days of ART within the past three months. Adherence was defined as a response of “no” to all of the questions. Non-adherence was defined as a response of “yes” to any of the questions.

Six measurements of social determinants were assessed as potential adherence predictors: (1) HIV knowledge; (2) Enacted stigma; (3) internalized stigma; (4) BTC; (5) Social support; and (6) Engagement in peer-to-peer HIV counseling. Table 1 summarizes the characteristics of each of the six measurements, and Supplemental Tables 1–8 provide the complete sample items associated with the evaluation of each measurement.

Table 1:

Measurements of the Six Assessed Social Determinants of ART Adherence

Variable	Description	Sample questions*	Values/Range	Comments	References
					Citation	Population where scales have been used/validated	Reliability coefficient
HIV knowledge	True/False questions adopted from the HIV Knowledge Questionnaire (HIV-KQ) pertaining to HIV testing and transmission	Coughing and sneezing do not spread HIV. A person can get HIV by sharing a glass of water with someone who has HIV.	0–18	Scores reflect the number of correct responses	HIV Knowledge Questionnaire (HIV-KQ) [20]	Low-income men and women	Cochran α: 0.75 to 0.89 depending on the sample
Enacted stigma	A 10-item scale: “Yes” or “no” response to a list of discriminatory acts participants may have experienced related to their HIV status.	Has a medical provider or hospital worker mistreated you because of your HIV? Have people looked at you differently because you have HIV?	0–10	Higher scores out of 10 stigma items correlate with increasing number of experienced discriminatory acts	India Stigma Index [21, 22]	Men and women in India	Cochran α: 0.80
Internalized stigma	A 9-item scale: Severity of the negative attributions experienced by participants, with responses ranging from 0 (not at all) to 3 (a great deal), reflecting severity.	How much do you feel that you should avoid holding a new infant because of your HIV? How much do you feel that you should avoid feeding children because of your HIV?	0–3	Mean score of 9 stigma items. Higher values reflect increased severity of internalized stigma.	India Stigma Index [21, 22]	Men and women in India
Barriers to Care	A 12-item scale: to what degree each structural BTC impacted participants’ lives, with two different scores: (i) index: total number of barriers (max 12) identified as at least “a slight problem”, and (ii) severity: extent to which each identified barrier affected participants (0-no problem, to 3-major problem)	Long distances to medical facilities and personnel. Medical personnel (e.g., physicians, nurses), who decline to provide direct care to persons with HIV/AIDS.	Index: 0–12	Index score refers to the total number of items identified as “at least a slight problem.”	Barriers to Care scale [23]	Women from 27 different countries
			Severity: 0–36	The severity score also takes into account the intensity of the barriers.
Social support	Questions about (i) satisfaction (responses ranging from very dissatisfied to very satisfied); and (ii) primary source of social support	In general, how satisfied are you with the overall support you get? What is your main source of social support?	Overall support satisfaction was reported as the percentage of those who responded, “very satisfied” and type of support was reported using frequencies.		AIDS Clinical Trial Group (ACTG) adherence baseline questionnaire [24]	Men and women on combination ART
Engagement in peer-to-peer HIV counseling	Participants recruited from NAP in Yangon and MPG in Yangon and Pathein engaged in PC (provided by a trained PLWH) rather than standard counseling (by a healthcare worker.	Did you receive counseling from a peer HIV positive counselor?	Binary value (PC or standard counseling)

^*Complete questions to each scale with frequencies of responses are provided in Supplemental Tables 1–8.

Statistical Analysis

The questionnaire was numerically coded without any personal identifiers. Sixty percent of the entered data was rechecked for reliability. The primary outcome of interest was ART adherence.

Data are presented using mean values and standard deviations for continuous variables, or frequencies and percentages for categorical variables. We performed T-tests (for continuous variables), and chi-square tests (for categorical variables) to assess unadjusted differences between adherent and non-adherent participants. The organization and type of organization (NGO vs. GO) form natural clusters in the data. Participants of the same site form natural clusters as they are subject to similar methods, treatments, and personnel which is more similar within the site than across sites.

We used multilevel models to estimate the effect of each of the six potential adherence predictors accounting for the hierarchical data structure, and adjusting for the other five predictors as well as important covariates including age, gender, education level, duration of illness, CD4 count, city, HIV knowledge, enacted stigma, internalized stigma, BTC, social support, and engagement in PC.

We fit generalized logistic mixed-effects models to estimate the effect of the variables of interest on the binary outcome of adherence accounting for the dependent observations within clusters naturally formed from the data collection procedure. We performed regression diagnostics to assess the overall fit of the models. We present results from a complete-case analysis. Missing values (<5%) were omitted and total numbers reflect the number of participants who responded to the adherence questions on the questionnaire. Due to the small percentage of missing values, specific imputation methods to address missing data were not applied. Statistical tests were assessed at α=5% level of significance. Analysis was conducted in R version 3.5.3 (R Development Core Team, 2013).

Results

Among 956 enrolled participants, mean age was 38.7 years, 52.4% were female and the average duration since HIV diagnosis was 5.2 years. The majority of patients (77%) achieved grade-school level education, 35.8% reported average CD4 count of <350 cells/ mm³, and 52.4% reported heterosexual intercourse as their mode of HIV transmission. Nearly half (49.5%) received PC prior to initiating ART, while the remainder received standard of care counseling provided by trained health workers (Table 2).

Table 2:

Demographic Characteristics by Reported Adherence

	Adherent (n=714)	Non-Adherent (n=242)	Total (n=956)
Sex
Male	288 (40.3)	124 (51.2)	412 (43.1)
Female	392 (54.9)	109 (45.04)	501 (52.4)
Age (in years)	38.5 ± 8.8	39.1 ± 9.5	38.7 ± 9.0
Education level
< 10th grade (highest grade of secondary school in Myanmar)	552 (77.3)	184 (76.0)	736 (77.0)
Passed 10th grade, GED	76 (10.64)	20 (8.26)	96 (10.0)
Some college/Degree Completed	77 (10.78)	31 (12.81)	108 (11.30)
Duration of Illness (in years)	4.99 ± 4.3	6.2 ± 4.8	5.3 ± 4.5
Median reported CD4 count in cells/mm3
<350	253 (35.4)	89 (36.8)	342 (35.8)
350–500	217 (30.4)	61 (25.2)	278 (29.1)
>500	217 (30.4)	75 (31.0)	292 (30.5)
City
Yangon	339 (47.5)	134 (55.4)	473 (49.5)
Pyay	67 (9.4)	20 (8.3)	87 (9.1)
Pathein	239 (33.5)	63 (26.0)	302 (31.6)
Myingyan	69 (9.7)	25 (10.213)	94 (9.8)
Participated in peer-HIV counseling	368 (51.5)	105 (43.4)	473 (49.5)
Mode of Transmission
Heterosexual intercourse	381 (53.4)	120 (49.6)	501 (52.4)
Homosexual intercourse	41 (5.7)	13 (5.4)	54 (5.7)
Intravenous Drug Use	70 (9.8)	22 (9.1)	92 (9.6)
Transfusion-related	77 (10.8)	28 (11.6)	105 (11.0)
Occupational exposure	20 (2.8)	13 (5.4)	33 (3.4)
Other	14 (2.0)	7 (2.9)	21 (2.2)
Refuse to answer	56 (7.8)	20 (8.3)	76 (8.0)

Footnote: Values are presented as mean±SD (Standard Deviation) for continuous and frequencies (%) for categorical variables. Abbreviations: GED, General Education Diploma.

Seventy-four percent of participants (714/956) reported being adherent to their ART in the past 3 months. Among the 242 who reported non-adherence, 44% reported forgetting and 81% reported being careless about taking medications; 17% reported that they stop taking their medications when they feel worse; 12% reported not taking their medication over the past weekend; 27% reported missing 1–2 doses, 4.5% 3–5 doses, and only one participant more than six doses in the past week; and only 8% reported missing more than two days of medications in the past 3 months.

Table 3 demonstrates unadjusted comparisons of the six potential adherence determinants. In terms of HIV knowledge (Supplemental Table 1), participants achieved a mean score 14.1 out of the 18 possible points demonstrating good knowledge of HIV testing and transmission, with ART adherent participants performing significantly better.

Table 3:

Unadjusted Comparisons of Examined Determinants of ART Adherence by Reported Adherence

	Total	Adherent	Non-adherent	P-Value
HIV Knowledge	14.1±2.91	14.3±2.69	13.7±3.30	0.011
Enacted Stigma Index	1.37±2.17	1.2±2.03	2.03±2.51	<0.001
Internalized Stigma	0.80±0.64	0.76±0.63	0.95±0.66	<0.001
Barriers to Care
Index	7.30±4.21	7.3±4.31	7.3±3.79	0.780
Severity	14.7±11.1	15.1±11.5	13.5±9.3	0.030
Social Support High Satisfaction	533 (53.8)	393 (55.8)	116 (48.3)	0.053
Engagement in peer-to-peer HIV counseling	493 (49.0)	368 (51.5)	105 (43.4)	0.034
Engagement in standard HIV counseling	513 (51.0)	346 (48.5)	137 (56.6)	0.034

Footnote: Values are presented as mean±SD (Standard Deviation) for continuous and frequencies (%) for categorical variables.

Enacted and internalized stigma were worse, with significantly higher scores, in those who were non-adherent to ART. The most frequently experienced enacted stigma was the status of being looked at differently by others for being HIV positive (30.2% total; 25.9% in adherent and 42.3% in non-adherent participants. Among all participants, other prevalent enacted sigma items include being mistreated by a hospital worker for one’s HIV status (17.2%), involuntary disclosure of one’s HIV status by a healthcare worker (16.8%), and inability to share eating utensils with family members because of HIV (15.9), Supplemental Table 2. The most commonly reported internalized stigma item was the feeling of paying for prior karma or sins by contracting HIV, which was the most intensely experienced stigma indicator among participants (65.6% total) and also the most common among both adherent (61.3%) and non-adherent (69.4%) participants (Supplemental Tables 3 and 4).

Out of 12 BTC, participants on average identified more than seven items on the index scale with nearly identical numbers between the adherent and non-adherent groups (Supplemental Table 5). However, severity of reported BTC was higher in the adherent compared to the non-adherent group (Supplemental Table 6). The most frequently reported BTC was lack of financial resources (78.6%), consistent in those adherent (78.0%) and non-adherent (80.2%).

With regards to social support, 53.2% of participants reported being very satisfied with their surrounding social support with no difference in the two adherence groups (Supplemental Table 7). The majority of participants (47.2%) reported family members as their main source of social support, followed by HIV counselor (30.2%), and doctors or nurses (12.1%); with a similar order among adherent and non-adherent participants (Supplemental Table 8) demonstrate complete frequencies of responses to each item of enacted stigma, internalized stigma, BTC, and social support scales). Finally, more participants who reported ART adherence engaged in PC.

After adjusting for age, gender, education level, CD4 count, duration of illness, and city, using mixed effects logistic regression analysis, experiences of enacted stigma and internalized stigma were associated with worse medication adherence (Table 4). Each unit of increase in the enacted and internalized stigma score, indicating worse stigma experiences, was associated with a 14% and 27% decrease in the odds of adherence respectively. Among the adjustment variables only sex and duration of HIV seemed to have a significant effect on ART adherence, with estimated ORs 1.74 (1.23, 2.45) for females, and 0.94 (0.91, 0.98) for people living longer with HIV.

Table 4:

Adjusted Effects of ART Determinants and Reported Adherence

Predictor	Odds Ratio (95% CI)
HIV Knowledge	1.02 (0.96, 1.08)
Enacted Stigma	0.86 (0.79, 0.92)
Internalized Stigma	0.73 (0.56, 0.95)
Barriers to Care Severity	0.96 (0.76, 1.21)
Social Support Satisfaction	0.72 (0.46, 1.12)
Engagement in Peer-to-Peer HIV Counseling	1.52 (0.97, 2.41)

Footnote: Results from a mixed-effects logistic regression model including all six important predictors, accounting for clustering within the same type of organization (GO vs NGO), and adjusting for age, gender, education level, duration of illness, CD4 count, and city. Abbreviations: ART, antiretroviral therapy; CI, confidence interval.

Discussion

The evaluation of social determinants associated with ART adherence in Myanmar is limited, yet important for care of PLWH. This study is the first to examine the impact of HIV knowledge, stigma, BTC, social support, and engagement in PC, on ART adherence among a large sample of adults living with HIV within the unique context of Myanmar. HIV-related stigma was found to be associated with reported lower ART adherence, a particularly important finding given rising numbers of patients initiating ART in the country, limited currently available ART regimens, and existing treatment monitoring challenges ¹⁵. These results promote characterizing and addressing HIV-related stigma and investing resources toward its mitigation in order to improve ART adherence and HIV care in Myanmar and similar settings.

Enacted stigma reflects overt acts of discrimination experienced by a person while internalized stigma refers to perceived negative sentiments related to one’s HIV diagnosis. The most frequently reported enacted stigma in this study was people viewing participants differently, which is consistent with prior literature ^17–19 in other resource-limited settings. The most common internalized stigma was participants feeling they were paying for prior karma or sins because of their HIV diagnosis. This likely reflects distinctive circumstances including the strong emphasis on religious beliefs and social conservatism in Myanmar compounded by decades of strict censorship. The influence of societal discrimination and the negative perceptions of HIV on care and quality of life among PLWH in Myanmar is likely much stronger compared to other regions. Data presented here are therefore unique and highlight the importance of developing regionally and culturally tailored scales to better evaluate HIV-related stigma within unique societal and religious settings toward eliminating discrimination against PLWH.

Both enacted and internalized stigma were significantly associated with worse reported ART adherence. These findings align well with studies on HIV-related stigma in both developed and developing countries ^{12, 20–22}. HIV-related stigma may potentiate poor quality of life and impede engagement in care. Moreover, cultural differences impact the type and severity of stigma experienced by PLWH resulting in reluctance to disclose high-risk behaviors, seek health services, and maintain ART adherence ^23–31. This can negatively impact HIV transmission, morbidity and mortality, particularly in high-risk groups. Our results emphasize the extent of this problem in Myanmar and encourage characterization of HIV stigma in the county to better understand the source and impact of specific stigma items and optimize resources, particularly religious institutions and leaders, to mitigate stigma and improve HIV adherence.

An unexpected finding was the proportion of self-reported good adherence in this study (74%), lower than in a previous smaller study in Myanmar during a similar time frame (84%) ¹⁴. In fact, actual adherence is likely even lower given the potential for reporting bias. This observation may have resulted from the strict adherence scale used, in which any score ≥1 was defined as non-adherent, or the uniqueness of our study population who may have felt more comfortable anonymously reporting non-adherence through the study questionnaire. The frequencies of specific responses on the non-adherence scale were consistent with other findings in Myanmar [8]. These consistencies help substantiate our results and the scale used to assess adherence. Interestingly, being female was associated with increased adherence while those with a longer duration of HIV had lower adherence. This contrasts prior literature ^32–34 and underscores the need to evaluate gender differences in stigma and whether treatment fatigue over time leads to reduced adherence. While our findings need to be validated by additional self-assessments and inclusion of objective adherence measures, they provide currently very limited adherence data across several cities in the country important for treatment monitoring, curtailing transmission, and reducing morbidity and mortality.

Contrary to our hypothesis and prior studies in other resource-limited settings ^{8, 9, 35–37}, HIV knowledge, BTC, and engagement in PC were not significantly associated with ART adherence. The lack of significant associations may highlight the uniqueness in Myanmar or may be due to the cross-sectional nature of this study utilizing a convenience sample. Additional longitudinal studies with more representative sampling are warranted. Nevertheless, the application of the primary variables within a single adjusted model revealed a predominant effect of stigma on ART adherence; stigma’s influence on adherence exceeds other important factors including social support and structural barriers to care. Our findings suggest that interventions focused on reducing stigma alone, perhaps with application of religious messages or inclusion of religious leaders and institutions, may increase the low ART adherence in this population.

This study has several limitations. First, we utilized a convenience sample which is not representative of PLWH in Myanmar. Second, the cross-sectional nature of our study limits the generalizability of the findings and does not allow for a proper comprehensive mediation analysis to better understand the causal relationships between the important determinants with the main outcomes of interest. Third, we did not incorporate important socio-demographic variables such as intravenous drug use, socioeconomic status, occupation, marital status, literacy level, and barriers to getting tested and learning one’s HIV status which might impact results ^{38, 39}. Forth, duration of HIV rather than of ART use was included as a co-variable, though the two are likely similar since patients are referred for ART upon diagnosis. Fifth, the study relied on self-reports, which though validated in various populations ^{40–43,44,45} and widely used ⁴⁶, are subject to bias and the scales were not validated in the local context. While self-reported adherence may overestimate actual adherence, the low adherence reported here may suggest more accurate reporting. Lastly, this study was conducted prior to the dissemination of viral load testing. Given the limited data from Myanmar on ART adherence and existing challenges associated with widespread use of viral load monitoring, this study remains relevant and informative.

Conclusion

This study augments the scarce literature available from Myanmar, notably as related to ART adherence as well as the relative influence of HIV-related stigma in comparison to other previously identified predictors of ART adherence. Additionally, our study offers a feasible approach to evaluating predictors of ART adherence within resource-limited settings where more objective measures such as widespread viral load monitoring is not yet available. As ART access is rolled out in the country, examining determinants of ART adherence is imperative for ensuring good clinical outcomes, particularly among PLWH who may be subject to various structural BTC, disease management challenges, and societal stigma. The reported low ART adherence and its association with stigma, beyond HIV knowledge, structural barriers to care, and social support, stress the importance and magnitude of the problem in the country, and its potential impact on health outcomes. Our findings call for the urgent need to continue to assess the prevalence and characterization of HIV-related stigma and develop ways to reduce it. Further, identifying disparities associated with stigma including access to services and employment opportunities are crucial. Such interventions would result in improved quality of life and health outcomes for PLWH in Myanmar and prevention of HIV transmission in the country.

List of Abbreviations

AIDS

Acquired Immunodeficiency Syndrome

ART

Antiretroviral Therapy

BTC

Barrier(s) to Care

GO

Governmental Organization

HIV

Human Immunodeficiency Virus

MPG

Myanmar Positive Group

NAP

National AIDS Programme

NGO

Non-Governmental Organization

PLWH

Persons/people living with HIV

PC

Peer-to-peer Counseling

PGK

Pyi Gyi Khin