Barriers for Antiretroviral Therapy Adherence and Viral Suppression in Members of the Key Population in Mumbai, India: Implications for Interventions.

BACKGROUND: Poor adherence to antiretroviral therapy (ART) is associated with poor virologic control and drug resistance in people living with HIV/AIDS. Some barriers to ART adherence are cost, lack of information, stigma, or dissatisfaction with health services. AIMS AND
OBJECTIVES: To study the association between barriers for ART adherence and viral suppression, and explore the role of "missing ART dose" as a potential mediator in high-risk groups.
MATERIALS AND METHODS: Demographic, clinical, and behavioral data from 50 "virally suppressed" (viral load [VL] <1000 copies/ml) and 48 "not suppressed" (VL > 1000 copies/ml) individuals belonging to the key population in Mumbai were collected. Sociodemographic, behavioral, and other characteristics were compared, and mediation analysis was used to identify the mediator in the pathway to viral suppression.
RESULTS: Those who had missed their ART at least once in the past three months (37% versus 60%, P = 0.03) and stayed alone were less likely to be virally suppressed (31% versus 69%, P = 0.002). Individuals who had negative perception about ART (adjusted odds ratio [aOR]: 0.11, 95% confidence interval [CI]: 0.02, 0.47; P = 0.002), poor ART-related knowledge/behaviors (aOR: 0.14, 95% CI: 0.03, 0.60; P = 0.007), and poor pill taking practices (aOR: 0.10, 95% CI: 0.02, 0.61; P = 0.01) were significantly less likely to be virally suppressed. The mediation pathway "adherence theme > missed ART in the past three months > viral suppression" was significant in these themes.
CONCLUSIONS: The factors associated with low viral suppression were knowledge/behaviors, perceptions about ART, and poor pill taking practices. Thus, it is important to provide correct information about ART, its effects, side effects, and potential limitations to marginalized population. Involving brothel keepers and Gurus (head of male-to-female transgendered people/Hijras clans), and technology enabled customized counseling sessions will be helpful. Copyright:

Introduction

Although India initiated antiretroviral therapy (ART) in the government sector in 2004, it was based on clinical guidelines. However, since 2017, India has opted for test and treat policy. Thus, all HIV-infected individuals are provided treatment at government ART cecenters[1] All individuals on ART are provided counseling about intake of medications, side effects, and regular follow-ups. In addition, mechanisms are in place to track those who are not regular with ART medications through regular adherence monitoring.

Poor adherence to ART is associated with poor virologic control and drug resistance in people living with HIV/AIDS (PLHAs).[234] The national program India also emphasizes on maintaining an adherence of more than 95% in those who have been started on ART. Studies have identified multiple barriers and facilitators for adherence to ART—globally as well as in India. The most common barriers were cost of ART and financial concerns.[567] The other common barriers are lack of information about ART, stigma, dissatisfaction with health care services, or overburdened healthcare services.[589] Side effects to medications, inconvenience about taking medications daily, and forget to take medications are additional common barriers commonly reported by PLHAs.[1011] Poor mental health and substance use have also been identified as other barriers.[1213]

Certain key populations, such as female sex workers (FSWs), men who have sex with men (MSM), male-to-female transgendered people/Hijras, and people who inject drugs may face additional barriers. For instance, authors have reported that lack of social support may be associated with depression; this may be further associated with poor adherence.[14] In addition, stigma[15] may result in avoiding taking medications in front of others. Alcohol use is another important factor associated with poor adherence.[16] Some of these key populations, particularly sex workers, may have to consume alcohol due to the insistence of their clients. Some of the additional barriers may be specific to these communities; many of them do not stay with family members and may lack social and family support. Furthermore, those in sex work may be afraid of losing clients; thus, they may avoid keeping medications in the place of stay/work.

Studies have also shown that PLHAs who experience stigma were less likely to be virally suppressed.[171819] Although some authors could not identify the exact mechanism, others have proposed that this may be due to its effect on health behaviors of PLHAs (such as effect on adherence and retention issues).[1820] Thus, it will be important to understand the effect that these adherence-related factors have on viral suppression in members of the key population in India. Knowledge of these will help us tailor our interventions for these groups. The HIV prevalence in India is high in certain groups that are at high risk for HIV infection; these groups form a part of the key population.[2122] If we can ensure viral suppression in this group, the chances of transmission to the bridge population (such clients of sex workers) and general population will reduce. With this background, we conducted the present study to examine the association between barriers for ART adherence and viral suppression in members of the key population, and explore the role of "missing ART dose" (having missed an ART dose in the past three months) as a potential mediator.

Materials and Methods

This is a secondary data analysis of 98 HIV-infected individuals from three types of key population (FSWs, MSM, and male-to-female transgendered people/Hijras) from ART center working under the aegis of Mumbai Districts AIDS Control Society.

Data Source

Demographic, clinical, and behavioral data from 50 individuals who had suppressed viral load (viral load [VL] <1000 copies/ml included cased with undetectable viral load) and 48 who did not have a suppressed viral load (VL ≥ 1000 copies/ml) before their adherence counseling session were included in the study. We abstracted the following data: 1) sociodemographic data (age, gender, typology of the key population, and type of targeted intervention); 2) clinical data (CD4 counts, viral loads, initiation of ART, duration of ART, and number of tablets in ART); factors related to ART intake and improving adherence (such as forgotten to take pills, remember the next date for ART attendance, factors/personnel that will help improve adherence), access to social support, and pill-taking practices (such missing a dose in the past three months and number of doses missed). In addition, they also responded to statements related to ART adherence. These statements were under the following themes: 1) perception about ART; 2) stigma related to ART intake; 3) ART knowledge and behaviors; 4) pill-taking practices; 5) access to ART center; 6) stress/mental health related issues; 7) and substance use [Figure 1].[810111323] The responses were collected on a three-point scale: Agree/Disagree/Neutral. All information was collected as a part of the adherence program in HIV-infected individuals. These individuals were a part of the Enhanced Adherence Counselling (EAC) Programme. Thus, those who were not virally suppressed were given adherence counseling and followed up. A repeat viral test was done on these individuals. For the present analysis, we have only used the baseline data of these individuals.

Figure 1

Figure showing barriers to ART adherence among key population members in Mumbai, India*. *Some responses to the individual questions are missing and the proportions are based on the total response for that question

Statistical Analysis

The primary outcome for our quantitative analysis was viral suppression (defined as < 1000 copies/ml according to the existing guidelines in India). We compared the sociodemographic, behavioral, and other characteristics in these two groups (viral suppressed and not suppressed). We estimated means and standard deviations (SDs), or medians and interquartile ranges (IQR) for linear variables. We estimated the proportions for categorical variables. The means were compared using the t-test, and the medians were compared using the Mann–Whitney Wilcoxon rank sum test. The proportions were compared using the Chi-square test or Fisher's exact test for low expected cell counts. We used logistic regression models that will be used to identify the factors associated with poor viral suppression. The main predictor variable for each model was the type of barrier to ART adherence (such as access to ART). The additional explanatory variables in these models were as follows: age, gender, duration of ART, ART regimen, and living condition (stays alone or not). We used the Akaike information criteria to assess the fit of these models.

We also did the mediation analysis to identify the mediator in the pathway to viral suppression. The mediator in the pathway was "missed ART in the past three months' [Figure 2]. This variable was considered as a behavior in the pathway to viral suppression. We built separate models for each of the adherence-related factors, which were significant in the logistic regression models. The mediation models were adjusted for all the variables included in the logistic models. Data analysis (including the mediation analysis) was done using Stata Version 15.1 (© StataCorp, College Station, TX, USA). We used the "medeff" program in Stata for the mediation analysis.[24252627]

Figure 2

Figure showing the proposed mediation pathway between barrier to ART adherence and viral suppression

The study was approved by the Ethics Committee of the Mumbai Districts AIDS Control Society (Ref No. 001/2019; Date: 25 March 2019).

Results

The mean age of the participants was 37.4 (8.5) years; it was not significantly different in those who were virally suppressed and those who were not. The proportion of key population included in the study were: FSWs—64%, MSM—17%, and male-to-female transgendered people/Hijras—18%. Most of them either lived alone (37%) or with parents. About 33% of the participants had not shared their HIV status with anyone; the proportion was similar in MSM and FSW (35%) and lower in male-to-female transgendered people/Hijras (22%). FSWs had shared their HIV status with their brothel keeper (Gharwali) and parents (19%). MSM had shared their status with their partners and friends (12%), and male-to-female transgendered people/Hijras had shared it with their Guru [head of the clan] (50%). Those who lived alone were significantly more likely not shared it with anyone compared with those lived with others (86% versus 2%, P < 0.001). The median (IQR) duration of ART was 2 (1, 5.79). About 39% had missed their ART at least once in the past three months [Table 1]. These patients were on the first-line ART according to the National guidelines. Most of the patients were on "Tenofovir + Lamivudine + Efavirenz" combination (57%) followed by "Zidovudine + Lamivudine + Nevirapine" (16%).

Table 1

The demographics, ART characteristics, and support required in 98 HIV positive individuals, Mumbai, India

	Total	Virally Suppressed <1000 copies/ml n (%)	Virally Not-Suppressed >_1000 copies/ml n (%)	P
Total	98 (100)	50 (51)	48 (49)
Characteristics
Age (mean [SD])	37.4 (8.5)	37.4 (9.6)	37.4 (7.2)	0.97
Gender
Female	63 (64)	30 (48)	33 (52)	0.12
Male	17 (17)	7 (41)	10 (59)
Malt-to-female transgender/Hijras	18 (18)	13 (72)	5 (28)
Living Condition
Immediate family (parents/spouse/partner)	34 (35)	25 (74)	9 (26)	0.005
Surrogate family (Gharwali/Guru)	16 (16)	8 (50)	8 (50)
Others (Distant Relative/friend etc.)	12 (12)	6 (50)	6 (50)
Alone	36 (37)	11 (31)	25 (69)
Not shared HIV status with anyone	32 (33)	10 (31)	22 (69)	0.009
Years of ART (median [IQR])	2 (1.00, 5.79)	1.65 (0.42, 3.45)	2.16 (1.02, 6.76)	0.03
Number of tablets (median [IQR])	1 (1, 2)	1 (1, 1)	1 (1, 2)	0.04
Missed ART in the past three months	38 (39)	14 (37)	24 (63)	0.03
What will help support adherence?
Treatment buddy	51 (52)	31 (61)	20 (39)	0.02
Community health worker	85 (87)	44 (52)	41 (48)	0.51
Telephonic reminders	33 (34)	19 (58)	14 (42)	0.47
Home visit by health care provider	61 (62)	32 (52)	29 (48)	0.07
Medication diary	14 (14)	2 (14)	12 (86)	0.03
Motivational interviewing/counselling	81 (83)	47 (58)	34 (42)	<0.001
Reminders such as pill box	10 (10)	1 (10)	9 (90)	0.04
Support groups	39 (40)	17 (44)	22 (56)	0.64
Personalised printed/written information	13 (13)	4 (27)	11 (73)	0.25

Those who had missed their ART at least once in the past three months were less likely to be virally suppressed compared with those who had not (37% versus 60%, P = 0.03). Those who stayed alone (31% versus 69%, P = 0.002) and had not shared their status with anyone (31% versus 69%, P = 0.006) were less likely to be virally suppressed compared with those who stayed with someone. Individuals who remembered the date of their next visit to the ART center were more likely to be virally suppressed compared with those who did not remember the date; the difference, however, was not significantly significant (64% versus 55%, P = 0.55). The common problems with ART intake were: forget to take medications after intake of alcohol (18%), fear of losing business due to others knowing the HIV status if the individual took medications in front of them (17%), treatment interrupting daily activities (15%), and the belief that they cannot take medications forever (15%), and hard to carry medications while leaving home (13%) [Figure 1]. Fear of being seen at the ART center (4%), unable to keep medications at home (3%), and unsuitable time of the ART center (5%) were not common in this group [Figure 1]. Majority of the participants reported that a community health worker (87%), motivational interviewing/counseling (83%), home visit by healthcare workers (62%), and treatment buddy (52%) will help support adherence. Treatment buddy and community health workers were ranked highly by these individuals.

After adjusting for age, gender, length of ART, type of ART, and living condition, we found that individuals who agreed with statements related to negative perception of ART (adjusted odds ratio [aOR]: 0.11, 95% confidence interval [CI]: 0.02, 0.47; P = 0.002), ART-related knowledge/behaviors (poor knowledge/behaviors) (aOR: 0.14, 95% CI: 0.03, 0.60; P = 0.007), and poor pill-taking practices (aOR: 0.10, 95% CI: 0.02, 0.61; P = 0.01) were significantly less likely to be virally suppressed. Access to the ART center was not significantly associated with viral suppression. In the unadjusted models, viral suppression was lower in those who reported ART-related stigma and stress/mental health concerns; however, in the adjusted models, the association was not statistically significant [Table 2].

Table 2

Unadjusted and adjusted estimates from logistic regression models for adherence factors associated with viral suppression, Mumbai, India

Thematic Indicator	Unadjusted Estimates		Adjusted Estimates*
	OR (95% Confidence Intervals)	P	OR (95% Confidence Intervals)	P
Negative perception about ART	0.22 (0.09, 0.55)	0.001	0.11 (0.02, 0.47)	0.002
ART stigma	0.32 (0.12, 0.83)	0.02	0.32 (0.09, 1.18)	0.08
ART knowledge/behaviors	0.22 (0.07, 0.67)	0.007	0.14 (0.03, 0.60)	0.007
Access to the ART center	0.78 (0.22, 2.74)	0.70	1.09 (0.13, 9.05)	0.94
Pill taking practices	0.41 (0.14, 1.20)	0.10	0.10 (0.02, 0.61)	0.01
Stress/Mental health	0.10 (0.01, 0.85)	0.04	0.11 (0.01, 1.42)	0.09
Substance use	0.38 (0.11, 1.32)	0.13	0.58 (0.11, 3.10)	0.52

In the mediation models, we found mediation pathway "adherence theme > missed ART in the past three months > viral suppression" was significant for all the three themes (perception about ART, pill intake practices, and knowledge and behaviors related to ART). The proportion of mediation was maximum for "pill intake practices" followed by "negative perception about ART" [Table 3].

Table 3

Table showing the Mediation Analysis Results for three themes significantly associated with low viral suppression, Mumbai, India

Models	Estimate	95% Confidence Intervals
Model 1: Negative Perception about ART (Theme 1)
Total Effect	−0.34	−0.50, −0.16
Direct effect	−0.25	−0.43, −0.08
Average Mediation
Factor 1 > missed ART in the past 3 months > viral suppression	−0.09	−0.19, −0.01
% Total effect mediated	25.8%
Model 2: Poor ART knowledge/behaviors (Theme 2)
Total Effect	−0.33	−0.51, −0.11
Direct effect	−0.25	−0.43, −0.06
Mediation effect
Factor 2 > missed ART in the past 3 months > viral Suppression	−0.07	−0.17, −0.01
% Total Effect Mediated	22.2%
Model 3: Pill Intake Practices (Theme 3)
Total Effect	−0.34	−0.51, −0.14
Direct effect	−0.23	−0.42, −0.04
Mediation effect
Factor 3 > missed ART in the past 3 months > viral Suppression	−0.11	−0.21, −0.01
% Total effect mediated	30.2%

Discussion

Thus, we found that knowledge and behaviors about ART, negative perception about ART, and poor pill-taking practices were significantly associated with lower viral suppression among members of key population in Mumbai. Furthermore, "missed ART in the past three months" was a significant mediator for these behaviors and practices. The proportion of individuals with viral suppression was significantly lower in those who stayed alone compared with those who did not. Access to the ART center was not significantly associated with viral suppression.

The WHO recommends EAC to improve treatment outcomes in PLHAs. Some of the components of this counseling are to assess the requirements, provide adherence counseling, educational sessions, and follow-up sessions.[28] As seen in our study, some of the common factors associated with low viral suppression were knowledge and perceptions about ART. Negative perceptions and poor knowledge about ART are important intrapersonal barriers for adherence.[293031] These individuals were also more likely to miss their ART dose in the past three months. Furthermore, they were also less likely to have a suppressed viral load. Although this may seem banal, it is important that treating physicians and healthcare providers emphasize the importance of ART medications, the side effects, the need for taking medications regularly, and their role in management of ART (such as they may not become negative—a perception seen in our population). This is particularly important for marginalized groups, such as sex workers, MSM, and male-to-female transgendered people. At the same time, it is important to empathize with them and understand the issues they face while taking ART. They may live in groups, and move regularly due to their profession, or may have their pills stolen by rogue elements at their place of work. Thus, their counseling session should not be the routine education/counseling session but rather an individual customized process, which evaluates their preparedness, knowledge, perception, and potential barriers in taking ART regularly.

"Pill intake practices" was the other important variable associated with viral load; those who agreed that they are unable to carry medicine or do not have a fixed time to take medications have significantly lower viral suppression; and the mediation via "missed ART" were also significant. Erratic schedule is known to be associated with poor adherence.[31] Ryan and Wagner have highlighted that maintaining a strict pill routine and adhering to it helps improve adherence.[32] They have also suggested that a single straight-jacket approach may not be appropriate for everyone and strategies should be developed individually. Although these are useful for the general population, adhering to strict routine may be difficult in these groups because of their profession. Most of the sex work activities may happen late in the evening or at night; the time may not be fixed. It may depend on the client, place of sex (own place, outside, or client's place). Although our population preferred community health worker and home visits by a healthcare provider, it may be difficult for them to visit each house every day or even every week. Thus, electronic adherence monitoring systems and interventions—such as computerized messages, cell phone follow-up messages, and electronic monitoring systems—along with individualized strategies will be useful for this population.[33343536] The time of the medication can be changed according to their work schedule.

Even though stigma, substance use, and stress were not associated with viral suppression in our study, these have been identified as important factors for adherence and should not be neglected in adherence counseling.[13151630] Furthermore, as seen in our analysis, people who stayed alone were less likely to be virally suppressed compared with those who stayed with someone. It is quite likely that existing support systems may play an important role in ART adherence. Interventions with the brothel keepers (Gharwaalis) or Gurus (cultural heads of the male-to-female transgendered people/Hijras family unit) will be a useful strategy. Although many studies have suggested access to care[37] as an important factor associated with adherence, it was not significant in our population. This could be because many of the members of the key population are associated with a community-based organization (CBO). This CBO generally ensures that they collect their medication from the designated ART centers.

The study had its limitations. These were self-reported behaviors. Hence, due to social desirability, people may have underreported their ART missing practices. Furthermore, the participants whose data have been included in the present analysis were a part of the targeted intervention programs and were exposed to all the components of the program. Thus, although these findings may be applicable to key populations, this may not completely apply to all PLHAs. Nonetheless, the study has provided useful information for intervention programs.

Conclusions

Thus, knowledge/behaviors, negative perceptions about ART, and poor pill-taking practices were associated with a low proportion of viral suppression; "missed ART in the past three months" was a significant mediator for them. In targeted interventions, it is especially important to provide correct information about ART, its effects, side effects, and potential limitations; these issues must be emphasized and discussed in detail before starting ART in the marginalized groups. Furthermore, their problems in adhering to the medications (such as routine of taking medication) should be enquired and solutions for these should be explored. Given that India has adopted the "test and treat" policy, the next main hurdle will be ensuring adherence in this population. Ensuring adequate adherence (>95%) will help in the maintenance of suppression of viral loads and avoid resistance to ART medications.[3839] This will be very useful for the overall ART program in India and achieve the 90–90-90 target.[40] Involving brothel keepers and Gurus, and customized counseling sessions with the use of technology will be helpful in this population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.